Assignment: Pharmacology

Submitted to: Dr. Humayun Jamil

Submitted by: Yusra Zahid
Mycotoxin effect on pituitary by exposure on animal; that
mycotoxin name, exposure, dose duration, effect, and mechanism
(biomarkers estimation)
I. Hepatotoxic effects of mycotoxin combinations in
mice:(1)
 Highlights:
 Hepatotoxicity of individual and combination AFB1, ZEA and DON in mice
was evaluated.
 AFB1 + DON showed a synergetic hepatotoxic effect, while AFB1 + ZEA
showed an antagonistic hepatotoxic effect in mice.
 Toxicological interactions need to be better understood to assess health
risks.
 Explanation:
 This study was performed to assess the individual and combined toxic
effects of aflatoxin B1 (AFB1), zearalenone (ZEA) and deoxynivalenol (DON)
within the liver of mice. A total of 56 4-week-old weanling female mice
were divided into seven groups (n = 8).
 For 2 weeks (duration), each group received an oral administration (site of
administration) of either solvent (control), AFB1, ZEA, DON, AFB1 + ZEA,
AFB1 + DON or ZEA + DON per day.
 The results showed that AFB1, ZEA and DON induced liver injury, indicated
by elevated relative liver weight, activities of alanine aminotransferase
(ALT) and/or aspartate aminotransferase (AST), as well as decreased
albumin (ALB) and/or total protein (TP) concentration in the serum
(effects). These mycotoxins also decreased hepatic total antioxidant
capacity (T-AOC), and/or increased the concentration of malondialdehyde
(MDA). Moreover, AFB1 + DON displayed synergistic effects, while AFB1 + 
ZEA displayed antagonistic effects on those parameters previously
described. Furthermore, the apoptotic potential was demonstrated
associated with an upregulation of the apoptotic genes Caspase-3 and Bax,
along with a downregulation of the antiapoptotic gene Bcl-2 in liver.
  In conclusion, this study provides a better understanding of the toxic effects
of AFB1, ZEA, DON, alone or in combinations on the liver of mice, which
could contribute to the risk assessment of these mycotoxins in food and
feed.
II. The determination of possible genetic damage to
women undergoing in vitro fertilization due to
infertility caused by the male factor:(2)
 Highlights:
 The possible genotoxic damage to women who were exposed to in vitro
fertilization was examined by genotoxicity tests.
 This is the first study covering four genotoxicity tests of IVF treatments for
patients by analyzing the lymphocytes.
 This study demonstrated that IVF treatment has weak risk at genetic level.
 Expalanation:
 In this study, we aimed at determining possible genetic damage to women
who were exposed to in vitro fertilization (IVF) due to infertility with male
factor.
 Four different genotoxicity tests were used in human lymphocytes in this
study with regard to chromosomal aberration (CA), sister chromatid
exchange (SCE), micronucleus (MN), and comet tests. There was a
statistically significant increase in sister chromatid exchange (SCE) test in
the study group compared with the control group. In addition, a higher rate
of MN frequency was determined only in the 21–30 age range study group
compared with the control group in the same age range.
 On the other hand, MN frequency did not differ significantly between the
control and total study groups. In addition, there was no significant
difference between the control group and the study group in terms of
mitotic (MI), replication (RI), and nuclear division (NDI) indices.
Furthermore, there was no statistically significant increase for
chromosomal aberration and DNA damage to the study groups. Our results
showed that in vitro fertilization treatments have a weak risk at the genetic
level in cultured human lymphocytes
III. Use of urinary renal biomarkers to evaluate the
nephrotoxic effects of melamine or cyanuric acid in
non-pregnant and pregnant rats:(3)
 Highlights:
 Multiplexed immunoassays were used to evaluate the effects of melamine
or cyanuric acid in pregnant and non-pregnant rats.
 Urinary renal biomarkers proved useful to detect kidney damage in rats
prior to the loss of function.
 This panel of biomarkers detected and differentiated the severity of
adverse effects induced by melamine or cyanuric acid.
 Results indicated that pregnant rats were more sensitive to the nephrotoxic
effects of melamine.
 Explanation:
 Although traditional assessments of renal damage detect loss of kidney
function, urinary renal biomarkers are proposed to indicate early changes
in renal integrity.
 The recent adulteration of infant formula and other milk-based foods with
melamine revealed a link between melamine ingestion and nephropathy.
Thus, the effects of melamine and related analogs (e.g., cyanuric acid)
should be assessed in other potentially sensitive groups.
 We evaluated whether urinary Kim-1, clusterin, and osteopontin could
detect the effects of high doses of melamine or cyanuric acid in pregnant
and non-pregnant female rats gavaged with 1000 mg/kg bw/day for 10
days. We demonstrate that these biomarkers can differentiate the severity
of effects induced by melamine or cyanuric acid. All melamine-treated
animals experienced adverse effects; however, pregnant rats were most
sensitive as indicated by increased SCr, BUN, and kidney weights, decreased
body weight, and presence of renal crystals. These effects coincided with
elevated urinary biomarker levels as early as day 2 of exposure. One
cyanuric acid-treated rat displayed effects similar to melamine, including
increased urinary biomarker levels. This work illustrates that these
biomarkers can detect early effects of melamine or cyanuric acid crystal-
induced nephropathy and further supports the use of urinary protein
immunoassays as a powerful, non-invasive method to assess
nephrotoxicity.
References:
(1)
https://www.sciencedirect.com/science/article/abs/pii/S0278691514004487
(2)
https://www.sciencedirect.com/science/article/abs/pii/S0278691514004323
(3)
https://www.sciencedirect.com/science/article/abs/pii/S0278691514004359