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Toxicology

Oxidative Stress and Dietary

Antioxidants

FIRST EDITION

Vinood B. Patel
School of Life Sciences, University of Westminster, London, United
Kingdom

Victor R. Preedy
Department of Nutrition and Dietetics, King’s College London, London,
United Kingdom
Department of Clinical Biochemistry, King’s College London, London,
United Kingdom
Table of Contents

Cover image

Title page

Copyright

Contributors

Preface
Part I: Toxicology and oxidative stress: General
aspects, agricultural and industrial chemicals

Chapter 1: Agrochemicals inhibiting mitochondrial respiration: Their

effects on oxidative stress

Abstract

Introduction

Mitochondrial complex I inhibitors

Mitochondrial complex II inhibitors

Mitochondrial complex III inhibitors

 Mitochondrial complex IV inhibitors

Mitochondrial complex V inhibitors

Applications to other areas of toxicology

Summary points

Chapter 2: Nanoparticle toxicity and reactive species: An overview

Abstract

Introduction

Nanoparticle-generated oxidative stress

Oxidative stress-associated nanoparticle toxicity

Nanoparticle-induced nitrosative stress

Nanoparticle-induced signal transduction in response to

oxidative stress

Summary

Applications to other areas of toxicology

Summary points

Chapter 3: Oxidative stress status and industrial discharges

Abstract

Introduction

Biotransformation
 Biomonitoring humans

Oxidative damage and genotoxicity

Levels of contaminants in the environment

Oxidative stress in lymphomagenesis

Concluding remarks

Utility for other toxicology areas

Summary points

Chapter 4: Terpene toxicity and oxidative stress

Abstract

Introduction

Researches on terpene toxicity and oxidative damage

Monoterpene toxicity and oxidative stress

Cytotoxicity and oxidative effects of sesquiterpenes, diterpenes,

and others

Applications to other areas of toxicology

Summary points

Chapter 5: Antioxidant status in pesticides-exposed agricultural

workers

Abstract

Introduction
 Occupational exposure to pesticides

Pesticides-induced oxidative stress

Antioxidant defense system

Role of antioxidants in therapeutic intoxication of pesticides

Prevention of health outcome of pesticides exposure among

agricultural workers

Applications to other areas of toxicology

Summary of important points and perspectives

Chapter 6: Antioxidant genes, the insecticide diazinon, and toxicity

Abstract

Introduction

Diazinon—An overview

Diazinon and the antioxidant gene expression pattern

Conclusion

Applications to other areas of toxicology

Summary points

Chapter 7: Dimethoate organophosphate insecticide toxicity and the

role of oxidative stress

Abstract

Introduction
 Toxicokinetic of dimethoate

Mechanism of toxicity

The role of oxidative stress

Neurological effects

Hepatotoxic effects

Renal effects

Reproductive and developmental effects

Pulmonary effects

Genotoxicity

Carcinogenicity

Exposure limits

Treatment regimen

Biological monitoring

Conclusion

The applications to other areas of toxicology

Summary points

Chapter 8: Oxidative stress in paraquat-induced damage to nervous

tissues

Abstract

Introduction
 Paraquat and Parkinson’s disease

How does paraquat reach the brain?

Mechanisms of paraquat-mediated neurotoxicity: A focus on

oxidative stress

Paraquat and the susceptibility of nigrostriatal neurons

Paraquat neurotoxicity is potentiated by maneb: Implications for

Parkinson’s disease

Paraquat neurotoxicity: Beyond nigrostriatal dopaminergic

system

Concluding remarks

Applications to other areas of toxicology

Summary points

Chapter 9: Glyphosate-based herbicides and oxidative stress

Abstract

Introduction

History and current uses of glyphosate

Chemistry and commercial formulations of glyphosate

Exposure

Toxicology and effects of glyphosate on nontarget organisms

Oxidative stress mechanisms triggered by glyphosate

Antioxidant response induced by glyphosate

 Consequences of glyphosate on human health: Chronic effects

Applications to other areas of toxicology

Summary points

Chapter 10: NRF2 and paraquat-induced fatal redox stress

Abstract

Introduction

The uptake and efflux of paraquat

Paraquat acts as an intracellular ROS generator

NRF2 is an antioxidant switch knob

Cytoprotective mechanisms of NRF2 against paraquat

NRF2 is a therapeutic target for paraquat toxicity

Summary points

Chapter 11: Pro- and antioxidant activity of chromium(III), iron(III),

molybdenum(III), or nickel(II)

Abstract

Introduction

Chromium

Antioxidant activity of chromium(III)—Applications to other areas

of toxicology

Iron
 Iron metabolism and ROS production in tumor cells

Nickel

Molybdenum

Summary

Applications to other areas of toxicology

Summary points

Chapter 12: Oxidative stress toxicity effect of potential metal

nanoparticles on human cells

Abstract

Acknowledgment

Introduction

Applications of metal nanoparticles

Cellular interaction with nanoparticles

Physicochemical characteristics of dependent toxicity

Oxidative stress induced by NPs

Titanium dioxide nanoparticles

Zinc oxide nanoparticles

Nickel oxide nanoparticles

Iron oxide nanoparticles

Cobalt oxide nanoparticles

 Copper oxide nanoparticles

Conclusion

Applications to other areas of toxicology

Summary points

Chapter 13: Oxidative stress and copper smelter workers

Abstract

Acknowledgment

Introduction

Effects of heavy metals on humans

Oxidative stress and heavy metals

Mechanism of toxicity of copper

Conclusion

Summary points

Chapter 14: Aluminum toxicity and oxidative stress

Abstract

Introduction

Toxicological profile for aluminum

Oxidative stress in health

Aluminum-induced oxidative stress

 Applications to other areas of toxicology

Summary points

Chapter 15: Methylmercury, oxidative stress, and neurodegeneration

Abstract

Introduction

Mechanisms of MeHg toxicity

MeHg and oxidative stress

Is there any association between MeHg exposure and

neurodegenerative diseases?

Conclusion

Application to other areas of toxicology

Summary points

Chapter 16: Arsenic-induced oxidative stress in reproductive

systems

Abstract

Introduction

Effects of arsenic on oxidative stress

Literature search on the reproductive toxicity of arsenic

The reproductive toxicity of arsenic

Effect of arsenic on the male reproductive system

 Effect of arsenic on the female reproductive system

Applications to other areas of toxicology

Conclusion

Summary points

Chapter 17: The role of oxidative stress in fluoride toxicity

Abstract

Introduction

Fluoride sources and human exposure

The excessive fluoride intake and oxidative damages

Applications to other areas of toxicology

Chapter 18: Environmentally relevant level of aflatoxin B1 and the

role of (non)oxidative immuno-/neurodysregulation and toxicity

Abstract

Acknowledgment

Introduction

Aflatoxins structure and properties—In general

Bodily oxidants and AFB1-induced oxidative stress

Distribution and public health concerns of AFB1

Biodegradation and metabolism of AFB1 in human

 CYPs and GST/GSH in human immune and neural cells and
role of AFB1

LC50 of AFB1 in immune and neural cells

AFB1-induced immunodysregulation/toxicity

AFB1-induced neurodysregulation/toxicity

Future applied prospects

Summary points

Chapter 19: A review on the oxidative effects of the fusariotoxins:

Fumonisin B1 and fusaric acid

Abstract

Introduction

Oxidative damage induced by fusariotoxins

Lipid peroxidation

Oxidative damage to proteins

Oxidative damage to nucleic acids

Mitochondrial dysfunction as a cause of FB1- and FA-induced

oxidative stress

Fusariotoxins effects on Keap-Nrf2-antioxidant pathway

Application to other areas of toxicology

Keypoints
Chapter 20: Mycotoxin exposure, oxidative stress, and lipid
peroxidation

Abstract

Introduction

Oxidative stress and lipid peroxidation

Lipid peroxidation

Susceptibility of lipids to peroxidation in vivo

Antioxidant defense system

Mycotoxin-induced oxidative stress

Lipid response to mycotoxin-induced oxidative stress

Oxidative stress-induced by multimycotoxin effects

Applications to other areas of toxicology

Summary points

Chapter 21: Toxicological effects of commonly used herbs and spices

Abstract

Introduction

Thyme, oregano, rosemary

Cinnamon

Clove

Peppermint
 Peppers

Basil

Garlic

Conclusion

Applications to other aspects of toxicology

Summary points

Chapter 22: Oxidative stress, Chinese herbals and toxicity: A focused

review with examples

Abstract

Acknowledgments

Introduction

Redox status in physiology and pathology

Mitochondrial oxidative stress

Chinese herbal medicine as source of antioxidant

Conclusions

Applications to other areas of toxicology

Summary points

Chapter 23: Alcohol toxicity: The role of oxidative stress

Abstract
 Introduction

Alcohol consumption and metabolism

Oxidative stress and drug toxicity

ROS and calcium interplay

Alcohol and oxidative stress

Heart and lung

Liver and gastrointestinal tract

Pancreas

Kidney

Immune system

Nervous system

Alcohol-induced pathologies

Applications to other areas of toxicology

Summary points

Chapter 24: Radiation and oxidative stress

Abstract

Radiation and oxidative stress

Medical radiation sources

Radiation protection
 Dosimetry

Summary points

Chapter 25: The impact of dimethyl sulfoxide on oxidative stress and

cytotoxicity in various experimental models

Abstract

Acknowledgments

Conflict of interest

Introduction

A general overview on DMSO

The concepts of oxidative stress and linked cytotoxicity

The impact of DMSO on oxidative stress

The impact of DMSO on cytotoxicity

Concluding summary

Summary points

Chapter 26: Statins, toxicity, and their adverse effects via oxidative
imbalance

Abstract

Acknowledgments

Introduction

Statins
 Toxicity and their adverse effects via oxidative imbalance
(adverse reactions by overdoses or prolonged administration of
statins)

Metabolism drug interactions

Concluding remarks

Chapter 27: The toxicological impact of some agents on glutathione

S-transferase and cholinesterase enzymes

Abstract

Introduction

Conclusions

Summary points

Chapter 28: Oxidative stress due to 5-fluorouracil and dietary

antioxidants

Abstract

Introduction

Oxidative stress induced by 5-FU

Dietary antioxidants combination strategy

Conclusion

Summary points

Chapter 29: AZT oxidative damage in the liver

 Abstract

Introduction

Oxidative damage

AZT-induced liver damage

Other aspects of AZT toxicity

Conclusions

Summary points

Part II: Antioxidants and toxicology: General

aspects, agricultural and industrial chemicals

Chapter 30: Effects of antioxidant nutrients on ionizing radiation-

induced oxidative stress

Abstract

Introduction

Biological effects of ionizing radiation

Antioxidant strategy: Natural antioxidants as radioprotectors

Antioxidant nutrients

Applications to other areas of toxicology

Summary points

Chapter 31: Linking metabolic profiling, resveratrol, the gut

microbiota, and antioxidant potential
 Abstract

Chemical properties, biosynthesis, and sources of resveratrol

General biological properties of resveratrol

Resveratrol as an antioxidant and prooxidant

Metabolic profiling and gut microbiota

Conclusions and further comments

Summary points

Chapter 32: Antioxidant and juçara fruits (Euterpe edulis Martius):

Potential applications in toxicology

Abstract

Introduction

Oxidative stress and antioxidants

Juçara fruits and their antioxidant compounds

Antioxidant capacity of juçara fruits: In vitro assays

Antioxidant capacity of juçara fruits: Cell culture assays

Antioxidant capacity of juçara fruits: In vivo studies

Applications to other areas of toxicology

Summary points

Chapter 33: White Butterfly (Clerodendrum volubile) leaves and

antioxidant potential in toxicity
 Abstract

Introduction

C. volubile plant taxonomy

Nutritional composition and phytochemical investigation of C.

volubile

Bioactive compounds in C. volubile

Toxicological evaluation on C. volubile

Antioxidant properties of C. volubile

Biological effects of C. volubile

Applications to other areas of toxicology

Summary points

Chapter 34: Vernonia amygdalina leaf and antioxidant potential

Abstract

Introduction

V. amygdalina as an antioxidant

Safety and toxicity of V. amygdalina

Conclusion

Summary points

Chapter 35: The antioxidant profile of two species belonging to the

genus Leonurus. Potential applications in toxicity
 Abstract

Introduction

Antioxidant profile of L. sibiricus L. and L. cardiaca L.

Potential uses of the toxicity of Leonurus genus

Applications to other areas of toxicology

Summary points

Chapter 36: Free radicals and coffee polyphenols: Potential

applications in toxicity

Abstract

Introduction

Free radicals and oxidative stress

Oxidative stress and chronic diseases

Polyphenols, health benefits, and application in toxicity

Coffee polyphenols against oxidative stress

Environmental oxidative stress and polyphenols

Summary points

Chapter 37: Amino acids ameliorate heavy metals-induced oxidative

stress in male/female reproductive tissue

Abstract

Introduction
 Oxidative stress-induced reproductive abnormalities

Amino acids as safe cytoprotective agents

Applications to other areas of toxicology

Summary points

Chapter 38: Betaine, heavy metal protection, oxidative stress, and the
liver

Abstract

Heavy metals hepatotoxicity

Betaine as a promising hepatoprotective agent

Oxidative stress as a pivotal mechanism for heavy metals-

induced toxicity in biological systems

Mechanisms of cytoprotection provided by betaine

Summary points

Chapter 39: An overview on the potential mechanisms of action of

N-acetyl-l-cysteine in hexavalent chromium-induced toxicity

Abstract

Introduction

Role of oxidative stress in Cr(VI)-induced toxicity

GSH-related issues in Cr(VI)-induced toxicity

N-Acetyl-l-cysteine
 N-Acetyl-l-cysteine use against Cr(VI)-induced toxicity

Future prospects

Applications to other areas of toxicology

Summary points

Chapter 40: Soft electrophile inhibition of selenoenzymes in disease

pathologies

Abstract

Introduction

Dietary selenium

Thioenzyme-dependent redox control

Glutathione and glutathione peroxidase

Thioredoxin and thioredoxin reductase

Selenoenzymes and cardiovascular disease

Selenoenzymes and neurological disease

Soft electrophiles as selenoenzyme inhibitors

Conclusion

Applications to other areas of toxicology

Summary points

Chapter 41: Selenium protection against cadmium and lead-induced

oxidative stress
 Abstract

Introduction

Cadmium toxicodynamics and toxicokinetics

Lead toxicodynamics and toxicokinetics

Combined toxicity of cadmium and lead

Mechanisms of selenium protection against lead and cadmium

toxicity

Selenium protective effects against cadmium toxicity

Selenium protective effects against lead toxicity

Selenium protective effects against combined toxicity of

cadmium and lead

Conclusions

Applications to other areas of toxicology

Summary points

Chapter 42: Protective effects of vitamin C against fluoride toxicity

Abstract

Introduction

Applications to other areas of toxicology

Literature search on protective effects of vitamin C against

fluoride toxicity

Fluoride toxicity
 Toxicity of fluoride on reproductive systems

Dental and skeletal toxicity of fluoride

Neurological toxicity of fluoride

Effects of vitamin C on oxidative stress

The role of vitamin C in fluoride-induced oxidative stress

Conclusion

Summary points

Chapter 43: Mushroom-related toxins, alpha amanitin, and usage of

antioxidants: Directions toward antioxidant capacity

Abstract

Introduction

α-Amanitin-containing mushroom toxins and their basic

characteristics

Mechanism of action of α-AMA

α-AMA-induced oxidative stress

α-AMA-induced inflammation and apoptosis

Clinical findings in poisoning with α-AMA-containing mushrooms

Diagnosis of poisoning with α-AMA containing mushrooms

Treatment of poisoning with α-AMA containing mushrooms

Applications to other areas of toxicology

 Summary points

Chapter 44: Mycotoxin deoxynivalenol and oxidative stress: Role of

silymarin and inulin protection

Abstract

Introduction

Oxidative stress of DON

Natural antioxidant agents

Applications to other areas of toxicology

Conclusion

Summary points

Chapter 45: Curcumin, antioxidant activity, and paracetamol toxicity

Abstract

Literature review

Conclusion

Summary points

Chapter 46: Role of semisynthetic flavonoids on cytotoxic

chemotherapy—Dual benefit to cancer patients?

Abstract

Introduction
Another random document with
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 schools. … The only important amendment to this Act was passed
in 1875, and provided that the legislative grant, instead of
being divided between the Protestant and Catholic schools as
heretofore, should in future be distributed in proportion to
the number of children of school age in the Catholic and
Protestant districts. Already immigration had begun to upset
the balance of numbers and power, and as the years went on it
became evident that the Catholics were destined to be in a
permanent minority in Manitoba. This trend of immigration,
which in 1875 made legislation necessary, has continued ever
since; and to-day the Catholics of the province number only
20,000 out of a total population of 204,000. No further change
was made in the educational system of Manitoba until the
memorable year of 1890. In that year the provincial
legislature boldly broke all moorings with the past, and,
abolishing the separate denominational schools, introduced a
system of free compulsory and unsectarian schools, for the
support of which the whole community was to be taxed. … To
test the legality of the change, what is known as Barrett's
case was begun in Winnipeg. It was carried to the Supreme
Court of Canada, and the Canadian judges by a unanimous
decision declared that the Act of 1890 was ultra vires and
void.
{60}
The city of Winnipeg appealed to the Privy Council, and that
tribunal in July 1892 reversed the decision of the Canadian
Court and affirmed that the Act was valid and binding. … The
second subsection of the 22nd section of the Manitoba Act
already quoted says: 'An appeal shall lie to the
Governor-General in Council from any Act or decision of the
legislature of the province, or of any provincial authority,
affecting any right or privilege of the Protestant or Roman
Catholic minority of the Queen's subjects in relation to
education.' But if the legislation of 1890 was intra vires,
and expressly declared to be so on the ground that it had not
prejudicially affected the position which the minority held at
the time of the Union, how could there be an appeal from it? …
The Governor-General, however, consented to refer the question
as to his jurisdiction to the courts of justice. What is known
as Brophy's case was begun, and in due course was carried to
the Supreme Court of Canada. The decision of that tribunal,
though not unanimous, was in accord with public expectation.
The majority of the judges felt that the previous judgment of
the Privy Council had settled the matter beforehand. The Act
of 1890 had been declared intra vires on the ground that it
had not interfered with the rights which the minority
possessed before the Union, and therefore there could be no
appeal from it. …

"Still the undaunted Archbishop of St. Boniface went on, and

for a last time appealed to that Judicial Committee of the
Privy Council which two years and a half before had so spoiled
and disappointed the Catholic hopes. In January 1894 the final
decision in Brophy's case was read by the Lord Chancellor. For
a second time the Lords of the Council upset the ruling of the
Supreme Court of Canada, and treated their reasoning as
irrelevant. It will be remembered that both the appellant
prelates and the Canadian judges had assumed that the clause
in the Manitoba Act, which conferred the right of appeal to
the Governor-General, was limited to one contingency, and
could be invoked only if the minority were robbed at any time
of the poor and elementary rights which they had enjoyed
before the Act of Union. But was the clause necessarily so
limited? Could it not be used to justify an appeal from
legislation which affected rights acquired after the Union? …
In the words of the judgment: 'The question arose: Did the
sub-section extend to the rights and privileges acquired by
legislation subsequent to the Union? It extended in terms to
"any" right or privilege of the minority affected by any Act
passed by the legislature, and would therefore seem to embrace
all the rights and privileges existing at the time when such
Act was passed. Their lordships saw no justification for
putting a limitation on language thus unlimited. There was
nothing in the surrounding circumstances or in the apparent
intention of the legislature to warrant any such limitation.'
… In other words, the dispute was referred to a new tribunal,
and one which was free to consider and give effect to the true
equities of the case. The Governor-General and his responsible
advisers, after considering all the facts, found in favour of
the Catholic minority, and at once issued a remedial Order to
the Government of Manitoba, which went far beyond anything
suggested in the judgment in Brophy's case. The province was
called upon to repeal the legislation of 1890, so far as it
interfered with the right of the Catholic minority to build
and maintain their own schools, to share proportionately in
any public grant for the purposes of education, and with the
right of such Catholics as contributed to Catholic schools to
be held exempt from all payments towards the support of any
other schools. In a word, the Governor-General and Sir
Mackenzie Bowell's Administration, exercising, as it were,
appellate jurisdiction, decided that the minority were
entitled to all they claimed. The Government of Manitoba,
however, had hardened their hearts against the minority in the
province, and refused to obey the remedial Order. …

"The refusal of the provincial Government 'to accept the

responsibility of carrying into effect the terms of the
remedial Order' for the first time brought the Parliament of
Canada into the field, and empowered them to pass coercive
legislation. A remedial Bill was accordingly, after an
inexplicable delay, brought into the Federal Parliament to
enforce the remedial Order. … The Cabinet recognised that the
Federal Parliament had no power to spend the money of the
province, and so all they could do was to exempt the minority
from the obligation to contribute to the support of schools
other than their own. The Bill bristled with legal and
constitutional difficulties; it concerned the coercion of a
province; it contained no less than 116 clauses; it was
introduced on the 2nd of March 1896, when all Canada knew that
the life of the Federal Parliament must necessarily expire on
the 24th of April. Some fifteen clauses had been considered
 when the Government admitted, what all men saw, the
impossibility of the task, and abandoned the Bill. … While the
fate of the remedial Bill was still undecided, Sir Donald
Smith and two others were commissioned by the Federal
Government to go to Winnipeg and see if by direct negotiations
some sort of tolerable terms could be arranged. … Sir Donald
Smith proposed that the principle of the separate school
should be admitted wherever there were a reasonable number of
Catholic children—thus, wherever in towns and villages there
are twenty-five Catholic children of school age, and in
cities where there are fifty such children, they should have
'a school-house or school-room for their own use,' with a
Catholic teacher. … In the event the negotiations failed; the
baffled Commissioners returned to Ottawa, and on the 24th of
April 1896 Parliament was dissolved. The Government went to
the country upon the policy of the abandoned Bill. On the
other hand, many of the followers of Mr. Laurier in the
province of Quebec pledged themselves to see justice done to
the Catholics of Manitoba, and let it be understood that they
objected to the remedial Bill only because it was not likely
to prove effective in the face of the combined hostility of
the legislature and the municipalities of the province. …
Catholic Quebec gave Mr. Laurier his majority at Ottawa. …

{61}

"When the Liberal party for the first time for eighteen years
found itself in power at Ottawa, Mr. Laurier at once opened
negotiations with Manitoba. The result was a settlement which,
although it might work well in particular districts, could not be
accepted as satisfactory by the Catholic authorities. It arranged
that where in towns and cities the average attendance of
Catholic children was forty or upwards, and in villages and
rural districts the average attendance of such children was
twenty-five or upwards, one Catholic teacher should be
employed. There were various other provisions, but that was
the central concession. … Leo the Thirteenth, recognising the
 difficulties which beset Mr. Laurier's path, mindful, perhaps,
also that it is not always easy immediately to resume friendly
conference with those who have just done their best to defeat
you, has sent to Canada an Apostolic Commissioner."

J. G. Snead Cox,
Mr. Laurier and Manitoba
(Nineteenth Century, April, 1897).

CANADA: A. D. 1895.
Northern territories formed into provisional districts.

"The unorganized and unnamed portion of the Dominion this year

was set apart into provisional districts. The territory east of
Hudson's Bay, having the province of Quebec on the south and
the Atlantic on the east, was to be hereafter known as Ungava.
The territory embraced in the islands of the Arctic Sea was to
be known as Franklin, the Mackenzie River region as Mackenzie,
and the Pacific coast territory lying north of British
Columbia and west of Mackenzie as Yukon. The extent of Ungava
and Franklin was undefined. Mackenzie would cover 538,600
square miles, and Yukon 225,000 square miles, in addition to
143,500 square miles added to Athabasca and 470,000 to
Keewatin. The total area of the Dominion was estimated at
3,456,383 square miles."

The Annual Register, 1895,

page 391.

CANADA: A. D. 1895.
Negotiations with Newfoundland.

Negotiations for the entrance of Newfoundland into the

federation of the Dominion of Canada proved ineffectual and
were abandoned in May. The island province refused the terms
proposed.
CANADA: A. D. 1896 (June-July).
Liberal triumph in Parliamentary elections.
Formation of Ministry by Sir Wilfred Laurier.

General elections held in Canada on the 23d of June, 1896,

gave the Liberal Party 113 seats out of 213 in the Dominion
House of Commons; the Conservatives securing 88, and the
Patrons of Industry and other Independents 12. Much to the
general surprise, the scale was turned in favor of the
Liberals by the vote of the province of Quebec,
notwithstanding the Manitoba school question, on which
clerical influence in the Roman church was ranged against that
party. The effect of the election was to call the Liberal
leader, Sir Wilfred Laurier, of Quebec, to the head of the
government, the Conservative Ministry, under Sir Charles
Tupper, retiring on the 8th of July.

CANADA: A. D. 1896-1897.
Policy of the Liberal Government.
Revision of the tariff, with discriminating duties
in favor of Great Britain, and provisions for reciprocity.

"The position of the Canadian Liberals, when they came into

power after the General Election of 1896, was not unlike that
of the English Liberals after the General Election of 1892.
Both Liberal parties had lists of reforms to which they were
committed. The English measures were in the Newcastle
Programme. Those of the Canadian Liberals were embodied in the
Ottawa Programme, which was formulated at a convention held at
the Dominion Capital in 1893. … A large part of the Ottawa
Programme was set out in the speech which the Governor-General
read in the Senate when the session of 1897 commenced. There was
then promised a measure for the revision of the tariff; a bill
providing for the extension of the Intercolonial railway from
Levis to Montreal; a bill repealing the Dominion Franchise Act
and abolishing the costly system of registration which goes
with it; and a measure providing for the plebiscite on the
Prohibition question. Neither of these last two measures was
carried through Parliament. Both had to be postponed to
another session; and the session of 1897 was devoted, so far
as legislation went, chiefly to the tariff, and to bills, none
of which were promised in the Speech from the Throne, in
retaliation for the United States Contract Labor Laws, and the
new United States tariff. …

"The new tariff was a departure from the tariffs of the

Conservative regime in only one important direction.
Protective duties heretofore had been levied on imports from
England, in the same way as on imports from the United States
or any other country. The 'National Policy' had allowed of no
preferences for England; and during the long period of
Conservative rule, when the Conservatives were supported by
the Canadian manufacturers in much the same way as the
Republican party in the United States is supported by the
manufacturing interests, the Canadian manufacturers had been
as insistent for adequate protection against English-made
goods, as against manufactured articles from the United States
or Germany. The Conservative party had continuously claimed a
monopoly of loyalty to England; but in its tariffs had never
dared to make any concession in favour of English goods. In
the new tariff, preferences for England were established; and
with these openings in favour of imports from Great Britain,
there came a specific warning from the Minister of Finance
that Canadian manufacturers must not regard themselves as
possessing a vested interest in the continuance of the
protective system. …

"When the Minister of Finance laid the tariff before the House
of Commons, he declared that the 'National Policy,' as it had
been tried for eighteen years, was a failure; and … claimed
that lowering the tariff wall against England was a step in
the direction of a tariff 'based not upon the protective
system but upon the requirements of the public service.'
During the first fifteen months of the new tariff, the
 concession to England consists of a reduction by one-eighth of
the duties chargeable under the general list. At the end of
that time, that is on the last of July, 1898, the reduction
will be one-fourth. The reductions do not apply to wines, malt
liquors, spirits and tobacco, the taxes on which are
essentially for revenue. While England was admitted at once to
the advantages of the reduced tariff, this tariff is not to be
applicable to England alone. In July, it was extended to the
products of New South Wales, the free-trade colony of the
British Australasian group; and any country can come within
its provisions whose government can satisfy the Comptroller of
Customs at Ottawa, that it is offering favourable treatment to
Canadian exports, and is affording them as easy an entrance
through its customs houses as the Canadians give by means of
the reciprocal tariff. It is also possible, under a later
amendment to the Tariff Act, for the Governor in Council to
extend the benefits of the reciprocal tariff to any country
entitled thereto by virtue of a treaty with Great Britain.
{62}
Numerous alterations were made in the general list of import
duties. Some of these involved higher rates; others lowered
the duties. But if the changes in the fiscal system had been
confined to these variations, the new tariff would not have
been noteworthy, and it would have fulfilled few of the
pledges made by the Liberals when they were in Opposition. It
owes its chief importance to the establishment of an inner
tariff in the interests of countries which deal favourably
with Canada."

E. Porritt,
The New Administration in Canada
(Yale Review, August, 1897).

CANADA: A. D. 1897 (June-July).

Conference of colonial premiers with
the British Colonial Secretary.
 See (in this volume)
ENGLAND: A. D. 1897 (JUNE-JULY).

CANADA: A. D. 1897 (October).

Self-government for the Northwestern Territories.

By an Act passed in October, a system of self-government,

going far towards the full powers of a provincial government,
but having some limitations, was provided for the Northwest
Territories.

CANADA: A. D. 1898 (January).

Encyclical Letter of the Pope on the Manitoba School Question.

On the report made by his delegate, Monsignor Merry del Val,

Pope Leo XIII. addressed an encyclical letter to the Roman
Church in Canada, concerning the duty of Catholics in the
matter of the Manitoba schools (see above: A. D. 1890-1896),
which was made public at Quebec on the 9th of January, 1898.
The letter has great general importance, as defining with
precision the attitude of the Church towards all secular
school systems. With a few unessential passages it is given in
what follows:

"It was with extreme solicitude," wrote the Pope, "that we

turned our mind to the unhappy events which in these later
years have marked the history of Catholic education in
Manitoba. … And since many expected that we should make a
pronouncement on the question, and asked that we should trace
a line of conduct and a way to be followed, we did not wish to
decide anything on this subject before our Apostolic delegate
had been on the spot, charged to proceed to a serious
examination of the situation, and to give an account to us of
the state of affairs. He has faithfully and diligently
fulfilled the command which we had given him. The question
agitated is one of great and exceptional importance. We speak
of the decision taken seven years ago by the parliament of
Manitoba on the subject of education. The act of Confederation
had secured to Catholic children the right of education in public
schools in keeping with their conscientious convictions. The
parliament of Manitoba abolished this right by contrary law.
By this latter law a grave injury was inflicted, for it was
not lawful for our children to seek the benefits of education
in schools in which the Catholic religion is ignored or
actively combated, in schools where its doctrine is despised
and its fundamental principles repudiated. If the Church has
anywhere permitted this, it was only with great reluctance and
in self-defense, and after having taken many precautions,
which, however, have too often been found unequal to parrying
the danger. In like manner one must at all cost avoid, as most
pernicious, those schools wherein every form of belief is
indifferently admitted and placed on an equal footing—as if in
what regards God and Divine things, it was of no importance
whether one believed rightly or wrongly, whether one followed
truth or falsehood. You well know, venerable brothers, that
all schools of this kind have been condemned by the Church,
because there can be nothing more pernicious nor more fitted
to injure the integrity of faith and to turn away the tender
minds of youth from the truth. … For the Catholic there is but
one true religion, the Catholic religion; hence in all that
concerns doctrine, or morality, or religion, he cannot accept
or recognize anything which is not drawn from the very sources
of Catholic teaching. Justice and reason demand, then, that
our children have in their schools not only scientific
instruction but also moral teachings in harmony, as we have
already said, with the principles of their religion, teachings
without which all education will be not only fruitless but
absolutely pernicious. Hence the necessity of having Catholic
teachers, reading books, and textbooks approved of by the
bishops, and liberty to organize the schools, that the
teaching therein shall be in full accord with Catholic faith
as well as with all the duties that flow therefrom. For the
rest, to decide in what institutions their children shall be
instructed, who shall be their teachers of morality, is a
right inherent to parental authority. When, then, Catholics
demand, and it is their duty to demand, and to strive to
obtain, that the teaching of the masters shall be in
conformity with the religion of their children, they are only
making use of their right; and there can be nothing more
unjust than to force on them the alternative of allowing their
children to grow up in ignorance, or to expose them to
manifest danger in what concerns the supreme interests of
their souls. It is not right to call in doubt or to abandon in
any way these principles of judging and acting which are
founded on truth and justice, and which are the safe-guards
both of public and private interests. Therefore, when the new
law in Manitoba struck a blow at Catholic education, it was
your duty, venerable brothers, to freely protest against the
injury and disaster inflicted; and the way in which you all
fulfilled that duty is a proof of your common vigilance, and
of a spirit truly worthy of bishops; and, although each one of
you will find on this point a sufficient approbation in the
testimony of his own conscience, learn, nevertheless, that you
have also our conscience and our approbation, for the things
which you sought and still seek to protect and defend are most
sacred. The difficulties created by the law of which we speak by
their very nature showed that an alleviation was to be sought
for in a united effort. For so worthy was the Catholic cause
that all good and upright citizens, without distinction of
party, should have banded themselves together in a close union
to uphold it. Unfortunately for the success of this cause, the
contrary took place. What is more deplorable still, is that
Catholic Canadians themselves failed to unite as they should
in defending those interests which are of such importance to
all—the importance and gravity of which should have stilled
the voice of party politics, which are of much less
importance. We are not unaware that something has been done to
amend that law. The men who are at the head of the federal
government and of the Province of Manitoba have already taken
certain measures with a view to decreasing the difficulties of
which the Catholics of Manitoba complain, and against which
 they rightly continue to protest.
{63}
We have no reason to doubt that these measures were taken from
love of justice and from a laudable motive. We cannot, however,
dissimulate the truth; the law which they have passed to
repair the injury is defective, unsuitable, insufficient. The
Catholics ask—and no one can deny that they justly ask—for
much more. Moreover, in the remedial measures that have been
proposed there is this defect, that in changes of local
circumstances they may easily become valueless. In a word, the
rights of Catholics and the education of their children have
not been sufficiently provided for in Manitoba. Everything in
this question demands, and is conformable to justice, that
they should be thoroughly provided for, that is, by placing in
security and surrounding with due safe-guards those
unchangeable and sacred principles of which we have spoken
above. This should be the aim, this the end to be zealously
and prudently sought for. Nothing can be more injurious to the
attainment of this end than discord; unity of spirit and
harmony of action are most necessary. Nevertheless since, as
frequently happens in things of this nature, there is not only
one fixed and determined but various ways of arriving at the
end which is proposed and which should be obtained, it follows
that there may be various opinions equally good and
advantageous. Wherefore let each and all be mindful of the
rules of moderation, and gentleness, and mutual charity; let
no one fail in the respect that is due to another; but let all
resolve in fraternal unanimity, and not without your advice,
to do that which the circumstances require and which appears
best to be done. As regards especially the Catholics of
Manitoba, we have every confidence that with God's help they
will succeed in obtaining full satisfaction. This hope is
founded, in the first place, in the righteousness of the
cause, next in the sense of justice and prudence of the men at
the head of the government, and finally in the good-will of all
upright men in Canada. In the meantime, until they are able to
obtain their full rights, let them not refuse partial
 satisfaction. If, therefore, anything is granted by law to
custom, or the good-will of men, which will render the evil
more tolerable and the dangers more remote, it is expedient
and useful to make use of such concessions, and to derive
therefrom as much benefit and advantage as possible. Where,
however, no remedy can be found for the evil, we must exhort
and beseech that it be provided against by the liberality and
munificence of their contributions, for no one can do anything
more salutary for himself or more conducive to the prosperity
of his country, than to contribute, according to his means, to
the maintenance of these schools. There is another point which
appeals to your common solicitude, namely, that by your
authority, and with the assistance of those who direct
educational institutions, an accurate and suitable curriculum
of studies be established, and that it be especially provided
that no one shall be permitted to teach who is not amply
endowed with all the necessary qualities, natural and
acquired, for it is only right that Catholic schools should be
able to compete in bearing, culture, and scholarship with the
best in the country. As concerns intellectual culture and the
progress of civilization, one can only recognize as
praiseworthy and noble the desire of the provinces of Canada
to develop public instruction, and to raise its standard more
and more, in order that it may daily become higher and more
perfect. Now there is no kind of knowledge, no perfection of
learning, which cannot be fully harmonized with Catholic
doctrine."

CANADA: A. D. 1898 (September).

Popular vote on the question of Prohibition.

Pursuant to a law passed by the Dominion Parliament the

previous June, a vote of the people in all the Provinces of
the Dominion was taken, on the 29th of September, 1898, upon
the following question: "Are you in favor of the passing of an
act prohibiting the importation, manufacture or sale of
spirits, wine, ale, beer, cider, and all other alcoholic
 liquors for use as beverages?" The submitting of this question
to a direct vote of the people was a proceeding not quite
analogous to the Swiss Referendum, since it decided the fate
of no pending law; nor did it imitate the popular Initiative
of Swiss legislation, since the result carried no mandate to
the government. It was more in the nature of a French
Plébiscite, and many called it by that name; but no Plebiscite
in France ever drew so real an expression of popular opinion
on a question so fully discussed. The result of the voting was
a majority for prohibition in every Province except Quebec,
Ontario pronouncing for it by more than 39,000, Nova Scotia by
more than 29,000, New Brunswick by more than 17,000, Manitoba
by more than 9,000, Prince Edward's Island by more than 8,000,
and the Northwest Territories by more than 3,000, while
British Columbia gave a small majority of less than 600 on the
same side. Quebec, on the other hand, shouted a loud "No" to
the question, by 93,000 majority. The net majority in favor of
Prohibition was 107,000. The total of votes polled on the
question was 540,000. This was less than 44 per cent of the
total registration of voters; hence the vote for Prohibition
represented only about 23 per cent of the electorate, which
the government considered to offer too small a support for the
measure asked for.

CANADA: A. D. 1898-1899.
The Joint High Commission for settlement of all unsettled
questions between Canada and the United States.

As the outcome of negotiations opened at Washington in the

previous autumn by the Canadian Premier, relative to the
seal-killing controversy, an agreement between Great Britain,
Canada and the United States was concluded on the 30th of May,
1898, for the creation of a Joint High Commission to negotiate
a treaty, if possible, by which all existing subjects of
controversy between the United States and Canada should be
settled with finality. Appointments to the Commission by the
three governments were made soon afterwards, Great Britain
 being represented by the Lord High Chancellor, Baron
Herschell; Canada by Sir Wilfred Laurier, Premier, Sir Richard
Cartwright, Minister of Trade and Commerce, and Sir Louis
Henry Davies, Minister of Marine and Fisheries; the United
States by Honorable John W. Foster, ex-Secretary of State,
Senator Charles W. Fairbanks, Senator George Gray,
Representative Nelson Dingley, and the Honorable John A.
Kasson, Reciprocity Commissioner. Senator Gray having been
subsequently appointed on the Commission to negotiate peace
with Spain, his place on the Anglo-American Commission was
taken by Senator Faulkner.
{64}
The Joint Commission sat first in Quebec and later in
Washington. Among the questions referred to it were those
relating to the establishment of the boundary between Alaska
and British Columbia; the issues over Bering Sea and the catch
of fur seals; the unmarked boundary between Canada and the
United States near Passamaqnoddy Bay in Maine and at points
between Wisconsin and Minnesota and Canada; the northeast
fisheries question, involving the rights of fishing in the
North Atlantic off Newfoundland and other points; the
regulation of the fishing rights on the Great Lakes;
alien-labor immigration across the Canadian-American border;
commercial reciprocity between the two countries; the
regulation of the bonding system by which goods are carried in
bond across the frontier and also the regulation of traffic by
international railways and canals of the two countries;
reciprocal mining privileges in the Klondyke, British North
America and other points; wrecking and salvage on the ocean
and Great Lakes coasting waters; the modification of the
treaty arrangement under which only one war vessel can be
maintained on the Great Lakes, with a view to allowing
warships to be built on the lakes and then floated out to the
ocean. The sessions of the Joint Commission were continued at
intervals until February, 1899, when it adjourned to meet at
Quebec in the following August, unless further adjournment
should be agreed upon by the several chairmen. Such further
 adjournment was made, and the labors of the Joint Commission
were indefinitely suspended, for reasons which the President
of the United States explained in his Message to Congress,
December, 1899, as follows: "Much progress had been made by
the Commission toward the adjustment of many of these
questions, when it became apparent that an irreconcilable
difference of views was entertained respecting the
delimitation of the Alaskan boundary. In the failure of an
agreement as to the meaning of articles 3 and 4 of the treaty
of 1825 between Russia and Great Britain, which defined the
boundary between Alaska and Canada, the American Commissioners
proposed that the subject of the boundary be laid aside and
that the remaining questions of difference be proceeded with,
some of which were so far advanced as to assure the
probability of a settlement. This being declined by the
British Commissioners, an adjournment was taken until the
boundary should be adjusted by the two Governments. The
subject has been receiving the careful attention which its
importance demands, with the result that a modus vivendi for
provisional demarcations in the region about the head of Lynn
Canal has been agreed upon [see (in this volume) ALASKA
BOUNDARY QUESTION] and it is hoped that the negotiations now
in progress between the two Governments will end in an
agreement for the establishment and delimitation of a
permanent boundary."

CANADA: A. D. 1899 (October).

Modus Vivendi, fixing provisional boundary line of Alaska.

See (in this volume)

ALASKA BOUNDARY QUESTION.

CANADA: A. D. 1899-1900.
Troops to reinforce the British army in South Africa.

A proposal from the Canadian government to assist that of the

Empire in its South African War was gratefully accepted in the
 early stages of the war, and a regiment of infantry called the
Royal Canadian, numbering a little more than 1,000 men, sailed
from Quebec, October 30. In the following January a second
contingent of more than 1,000 men was sent to the field. This
latter comprised squadrons of mounted rilles and rough-riders,
and three batteries of field artillery. In the same month the
Canadian government accepted an offer from Lord Strathcona to
raise, equip and transport at his own expense a body of 500
mounted men from the Northwest.

CANADA: A. D. 1900 (November).

General election.

The general election of members of the Dominion House of

Commons was held November 7, resulting as follows:

Provinces. Liberal. Conservative.

Independent. Total.

Nova Scotia. 15 5
0 20
New-Brunswick. 9 5
0 14
Prince Edward Island. 3 2
0 5
Quebec. 57 8
0 65
Ontario. 33 54
5 92
Manitoba. 2 3
2 7
Northwest Territories. 2 0
2 4
British Columbia. 3 2
1 6

Totals. 124 79
10 213

As in the election of 1896, the Liberal Ministry of Sir

Wilfred Laurier found its strong support in the province of
Quebec. Its party suffered unexpected losses in Ontario. The
slight meaning of the election was summed up by Professor
Goldwin Smith as follows: "The net result of the elections
seems to be a Government resting on French Quebec and an
Opposition resting on British Ontario. The minor provinces
have been carried, as usual, by local interests rather than on
general questions. Apart from the distinction of race between
the two great provinces and the antagonism, before dormant but
somewhat awakened by the war, there was no question of importance
at issue between the parties. Both concurred in sending
contingents to South Africa. The Liberals, though they went in
at first on the platform of free trade—at least, of a tariff
for revenue only—have practically embraced protection under
the name of stability of the tariff, and are believed to have
received from the protected manufacturers contributions to
their large election fund. The other special principles, such
as the reduction of expenditure and discontinuance of the
bonus to railways, proclaimed by Liberals before the last
election, have been dropped. So has reform of the Senate. It
is not likely that the Liberal victory will be followed by any
change either in legislation or government, or by any special
reform. Mr. Bourassa and Monet, of the French-Canadian members
who protested against the contingent, have been re-elected.
Great as may be the extent and warmth of British feeling, the
statement that Canadians were unanimously in favour of
participation in the war must not be taken without
qualification. For myself, I felt that so little principle was
at stake that I voted for two Conservatives on their personal
merits."
{65}

CANAL, The new Bruges.

See (in this volume)

BRUGES: A. D. 1900.

CANAL, The Chicago Drainage.

See (in this volume)

CHICAGO: A. D. 1900.

CANAL, City of Mexico Drainage.

See (in this volume)

MEXICO: A. D. 1898.

CANAL, The Elbe and Trave.

See (in this volume)

GERMANY: A. D. 1900 (JUNE).

CANAL, Interoceanic, The Project of the: A. D. 1581-1892.

The early inception of the project.
Movements towards its realization.

"The thought of uniting the two great oceans by means of a

canal across the American isthmus sprang up, as is known, from
the moment the conviction was reached that the passage which,
from the days of Columbus, was thought to exist towards the
Southern Sea, was not a reality. … Nevertheless the first
survey of the land was not carried out until the year 1581,
when, in obedience to superior instructions, Captain Antonio
Pereira, Governor of Costa Rica, organized an expedition and
explored the route by way of the San Juan river, the lake, and
the rivers emptying into Gulf Nicoya, Costa Rica. Thirty-nine
years later Diego de Mercado submitted to King Philip III his
famous report of January 23, 1620, suggesting the route by the
river and lake, and thence through Costa Rican territory along
the Quebrada or Barranca Honda to Salinas Bay, then called
Puerto del Papagayo. Either because the magnitude of the
undertaking was at that time superior to the necessities of
trade, or, as was said, because Spain considered the canal
antagonistic to her interests, the era of independence arrived
without the execution of the project ever having been entered
upon. After independence the Congress of Central America, in
which Costa Rica and Nicaragua were represented as States of
the Federation which succeeded the Colonial Government,
enacted on June 16, 1825, a decree providing for the
construction of the canal, and in that same year Don Antonio
José Cañas, Diplomatic Representative of Central America in
Washington, addressed the Secretary of State, Mr. Henry Clay,
informing him of this resolution and stating that: 'A company
formed of American citizens of respectability was ready to
undertake the work as soon as a treaty with the United States
insuring the coöperation of the latter was signed; that he was
ready to enter into negotiations for the treaty, and that
nothing would be more pleasant for Central America than to see
the generous people of the United States joining her in the
opening of the canal, sharing the glory of the enterprise, and
enjoying the great advantages to be derived from it.' The
Government of Central America could not carry the undertaking
into effect, notwithstanding that among the means employed to
reach the desired result there figures the arrangement
concluded with the King of Holland in October, 1830. But,
though the hopes centered in the undertaking were frustrated,
to the honor of Central America the declarations of that
Congress, which constitute, like the concession for the canal
itself, one of the loftiest public documents ever issued by
any nation of the earth, have become a matter of record. The
Central American Federation dissolved, this important matter
attached to Nicaragua and Costa Rica directly, and the
boundary line between the two republics having been determined