Experimental and Toxicologic Pathology 64 (2012) 487–493

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Experimental and Toxicologic Pathology

journal homepage: www.elsevier.de/etp

Protective effect of curcumin on cypermethrin-induced oxidative

stress in Wistar rats
Palanisamy Sankar, Avinash G. Telang ∗ , Ayyasamy Manimaran
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar 243122, Bareilly, Uttar Pradesh, India

a r t i c l e i n f o a b s t r a c t

Article history: The aim of present study was to investigate the protective effect of curcumin on cypermethrin-induced
Received 8 July 2010 changes in blood biochemical markers and tissue antioxidant enzyme in rats. Rats were divided into
Accepted 1 November 2010 six groups of six each: group I used as control and II and III groups were used as vehicle control. While,
groups IV, V and VI were orally treated with curcumin (100 mg/kg body weight), cypermethrin (25 mg/kg
Keywords: body weight) and cypermethrin plus curcumin, respectively for 28 days. Serum biochemical markers
Cypermethrin
were measured in the serum, and the levels of lipid peroxidation and antioxidant enzyme activity were
Curcumin
determined in the liver, kidney and brain. Cypermethrin administration caused elevated level of blood
Oxidative stress
Antioxidants
biochemical markers in serum and lipid peroxidation in liver, kidney and brain. While the activities
Rats of non-enzymatic and enzymatic antioxidants levels were decreased except superoxide dismutase in
liver, kidney and brain tissues. The presence of curcumin with cypermethrin significantly decreased the
blood biochemical markers and lipid peroxidation but significantly increased the reduced glutathione,
catalase and glutathione peroxidase level and preserved the normal histological architecture of the liver,
kidney and brain. Our results indicate that curcumin can be potent protective agent against cypermethrin-
induced biochemical alterations and oxidative damage in rats.
© 2010 Elsevier GmbH. All rights reserved.

1. Introduction on pesticides show that their toxicity is linked to different mech-

At present, synthetic pyrethroids are highly active insecticides
which account for 30% of insecticides used globally (Prasanth and
Rajini, 2005). There are serious concerns on the potential risks of
exposure to pyrethroid insecticides with increasing production and
application (Adelsbach and Tjeerdema, 2003). Cypermethrin (CYP)
is a member of the family of synthetic pyrethroids, belongs to type
II class pyrethroids and is widely used in agricultural and other
domestic applications. Accidental exposure with pyrethroids in
human and animals result from advertent use. Populations at high-
est risk of high dose exposure are producers, hygienic and pesticide
workers, and small farm owners applying CYP for plant protection;
low dose exposure originates mainly from the household appli-
cation of insecticides, contaminated food and water (Gorell et al.,
1998). CYP can be found in trace amounts or at higher concentra-
tions in soil and air. In mammals, CYP can accumulate in body fat,
skin, liver, kidneys, adrenal glands, ovaries, lung, blood, and heart
(Hall et al., 1980; Manna et al., 2004). CYP is highly hydrophobic
compounds and this suggests that their action in biological mem-
branes might be related to association with integral proteins and
with phospholipids (Michelangeli et al., 1990). Previous studies
∗ Corresponding author. Tel.: +91 581 2300291; fax: +91 581 2300361.
E-mail address: agtelang@rediffmail.com (A.G. Telang).
anisms, including reactive oxygen species (ROS) generation and
oxidative stress (Gupta et al., 1999). CYP and other pyrethroids
are metabolized in the liver via hydrolytic ester cleavage and
oxidative pathways by the CYP-450 enzymes yield ROS, which
may be responsible for oxidative stress in mammals (Floodstrom
et al., 1988; Klimek, 1990). The ROS directly react with cellular
biomolecules; damage lipids, proteins and DNA in cells and that can
ultimately lead to cell death. Pyrethroids are rapidly metabolized in
mammals, and several studies have shown that CYP damages the
brain, liver, kidney, and erythrocytes by causing oxidative stress
(Zegura et al., 2004; Giray et al., 2001; Kale et al., 1999).
During the past few years, estimation of free radical gener-
ation and antioxidant defense has become an important aspect
of investigation in mammals (Zini et al., 1993). A positive cor-
relation has been established between dietary supplementation
with certain vegetables and plant products and the reduction of
toxic effects of various toxicants and environmental contaminants
(Nandi et al., 1997). Plant products are known to exert their protec-
tive effects by scavenging free radicals and modulating antioxidant
defense system. Curcumin (CMN) (diferuloylmethane), a yellow
orange dye derived from the rhizomes of Curcuma longa turmeric,
is used as a spice and food-coloring agent in cooking (Joe et al.,
2004: Maheshwari et al., 2006). Curcumin represents a class of anti-
inflammatory and antioxidants reported to be a potent inhibitor of
ROS formation (Venkatesan et al., 2000; Biswas et al., 2005). Reddy

0940-2993/$ – see front matter © 2010 Elsevier GmbH. All rights reserved.
doi:10.1016/j.etp.2010.11.003
488 P. Sankar et al. / Experimental and Toxicologic Pathology 64 (2012) 487–493
and Lokesh (1994) indicated that CMN is a potent scavenger of a
variety of ROS including superoxide anion radicals and hydroxyl
radicals. CMN administration has been reported to prevent the
arsenic, gentamicin and acetaminophen-induced oxidative stress
in rats (Fatma et al., 2009; Farombi and Ekor, 2006; Cekmen et al.,
2009a,b). CMN also prevent the free radical formation in myocardial
ischemia in rats (Manikandan et al., 2004) and paraquat induced
lung injury (Venkatesan, 2000). Based on the above considerations,
the goal of the present study was to determine the possibilities of
CMM in preventing or minimizing the serum biochemical alter-
ations and oxidative stress induced by subacute administration of
CYP in rats.
2. Materials and methods
2.1. Experimental animals
The study was conducted in adult male Wistar rats (6–8 weeks,
100–120 g) procured from the Laboratory Animals Resources Sec-
tion of the Institute. Animals were maintained under standard
management conditions and handled as per the Institute Ani-
mal Ethics Guidelines. Rats were given standard rat feed and
water ad libitum throughout the experiment. All the animals were
quarantined for a period of at least 7 days before beginning of
the experiment. The animals were handled and the study was
conducted in accordance with the Institute guide lines for the pro-
tection of animal welfare.
2.2. Chemicals
Cypermethrin (CYP; 96%) was a kind gift from Gharda chemi-
cals, Mumbai. CMN was purchased from M/s Sigma Chemicals, USA.
All other chemicals used were of analytical grade from E. Merck,
Germany and India; Sigma Chemicals, USA and SRL Chemicals,
India.
2.3. Dose selection
CYP was dissolved in ground nut oil and administered orally for
28 days, at a dose rate of 25 mg/kg body weight/day (1/10 of LD50;
Cantalamessa, 1993) by oral gavage. CMN was dissolved in 1% gum
acacia and given orally for 28 days, at a dose rate of 100 mg/kg body
weight/day. CMN was administered 1 h prior to CYP treatment.
2.4. Experimental design
Rats were divided into 6 groups of 6 animals each. Control rats
were given water (group I), while groups 2 and 3 were given once
equivalent amount of ground nut oil and gum acacia (1%; vehi-
cle control), respectively. Rats of group 4 were administered CYP
(25 mg/kg, orally) daily for 28 days. Group 5 was administered CMN
(100 mg/kg, orally) daily for 28 days. Group 6 was administered CYP
(25 mg/kg, orally) and CMN (100 mg/kg, orally) daily for 28 days.
Body weights of rats were recorded initially and at the end of the
experiment. All the animals were observed daily for the presence of
clinical signs of toxicity during the entire period of the study. Rats
were sacrificed at the end of the exposure period. Blood was col-
lected by heart puncture from each rat in a dry, clean and sterilized
test tube, and allowed to clot. The sera samples were preserved at
−20 ◦ C until the analysis was performed. Liver, kidney and brain
were excised, washed with ice cold normal saline and used for
histopathological examination and oxidative stress assay.
2.5. Serum biochemical estimations
The activity of alanine amino transferase (ALT), aspartate amino
transferase (AST) and level of blood urea nitrogen (BUN) and cre-
atinine estimations were carried out using commercially available
kits (Span Diagnostics Ltd; India).
2.6. Assessment of oxidative stress and antioxidant enzyme
activity
Estimations of different oxidative stress-related biochemical
parameters in liver, kidney and brain were carried out. A 200 mg
of sample was taken in 2 ml of ice-cold phosphate buffer saline.
Another 200 mg of sample was separately taken in 2 ml of 0.02 M
EDTA for reduced glutathione (GSH) estimation. The homogenate
(10%) prepared with homogenizer (IKA, Germany) under ice-cold
condition was centrifuged for 10 min at 3000 rpm and the super-
natant was stored at −20 ◦ C until assay.
Lipid peroxidation (LPO) was evaluated in terms of malondi-
aldehyde (MDA) production (Shafiq-u-Rehman et al., 1984). GSH
content was evaluated by the method of Sedlak and Lindsay (1968).
Catalase (CAT) activity was assayed by the method as described
by Aebi (1983). The activity of superoxide dismutase (SOD) was
measured as per the method of Madesh and Balasubramanian
(1998). Glutathione peroxidase (GPx) activity was determined by
the method of Paglia and Valentine (1967). The protein content was
estimated by the method of Lowry et al. (1951) using bovine serum
albumin as standard.
2.7. Histopathology
Representative pieces of liver, kidney and brain were collected
and fixed in 10% neutral buffered-formalin. After proper fixation
(48 h), tissues were cut into thinner pieces (2–3 mm thick). These
samples were embedded in paraffin blocks. Sections of about 5 ␮m
were cut, stained with hematoxylin and eosin by the standard
method, and examined under light microscope (Luna, 1968).
2.8. Statistical analysis
Data have been expressed as mean ± SEM. The change in CYP
mediated effects was compared to the control values, while CYP
plus CMN mediated alterations was compared with the CYP group.
Statistical analysis of data was performed using GraphPad InStat.
Data were analyzed by ANOVA and means were compared with
Tukey multiple comparison test. A value of p < 0.05 was considered
statistically significant.
3. Results
3.1. Body weight
Clinical signs of toxicity such as slight nervousness, mild depres-
sion and abnormal gait were observed in cypermethrin-exposed
rats. The animals of other groups including those treated with CYP
plus CMN did not exhibit any apparent signs of toxicity. There was
no mortality in rats with any of the treatments. At term, CYP caused
significant reduction in body weights of animals treated with CYP
alone as compared to control group (Table 1). The presence of
CMN with CYP significantly increased the body weight as com-
pared to CYP alone treated rats. There were no differences in any of
parameters between the water and vehicle control group (results
are not shown); therefore, all comparisons are made to the water
control.
 P. Sankar et al. / Experimental and Toxicologic Pathology 64 (2012) 487–493 489

Table 1
Effect on body weight (g) following 28-days exposure with cypermethrin and cyper-
methrin plus curcumin.

Group Dose Body weight (g)

0 day 28 days

Control – 125.83 ± 2.39 227.50 ± 4.23

CMN 100 mg/kg 126.67 ± 3.07 223.50 ± 4.43
CYP 25 mg/kg 127.13 ± 1.54 199.16 ± 3.00a
CYP + CMN 25 + 100 mg/kg 125.00 ± 1.83 213.67 ± 2.11b

Values are represents mean ± SEM of 6 rats. Significant differences are indicated by
superscript a: compared to control (p < 0.05), superscript b: compared to CYP group
(p < 0.05). C: control, CMN: curcumin, CYP: cypermethrin.

3.2. Effects on serum biochemical markers

AST and ALT are indicators of hepatic function. Compared to the
control group, the CYP treated group had significantly elevated AST
and ALT in serum (Fig. 1A and B). The levels of BUN and creatinine
were significantly elevated by the CYP exposure in serum (Fig. 1C
and D). When the CYP plus CMN-treated group was compared to
the CYP-treated group, they had significantly lower AST, ALT, and
BUN levels.
Fig. 2. Effects of 28 days oral administration of CYP, CMN and CYP plus CMN on
lipid peroxidation level of liver, kidney and brain in male rats. Each bar represents
mean ± SEM of 6 rats. Significant differences are indicated by superscript a: com-
pared to control, superscript b: compared to CYP group. C: control, CMN: curcumin,
CYP: cypermethrin, CMN at 100 mg/kg and CYP at 25 mg/kg.
presence of CMN with CYP caused reduction in the elevated tissue
LPO in liver, kidney and brain tissues.

3.3. Effects on LPO 3.4. Effects on GSH content

Fig. 2 depicts the results of LPO in liver, kidney and brain. LPO Effects on the GSH in liver, kidney and brain are presented in
was measured as MDA concentration. Significant enhancement was Fig. 3. CYP treatment significantly decreased reduced glutathione
observed in LPO in the tissues examined after CYP exposure. The level in liver, kidney and brain tissues. Simultaneous treatment

Fig. 1. Effects of 28 days oral administration of CYP, CMN and CYP plus CMN on (A) aspartate aminotransferase, (B) alanine aminotransferase, (C) blood urea nitrogen and (D)
creatinine activities in serum of male rats. Each bar represents mean ± SEM of 6 rats. Significant differences are indicated by superscript a: compared to control, superscript
b: compared to CYP group. C: control, CMN: curcumin, CYP: cypermethrin, CMN at 100 mg/kg and CYP at 25 mg/kg.
490 P. Sankar et al. / Experimental and Toxicologic Pathology 64 (2012) 487–493
Fig. 3. Effects of 28 days oral administration of CYP, CMN and CYP plus CMN
on reduced glutathione of liver, kidney and brain in male rats. Each bar repre-
sents mean ± SEM of 6 rats. Significant differences are indicated by superscript a:
compared to control, superscript b: compared to CYP group. C: control, GN CMN:
curcumin, CYP: cypermethrin, CMN at 100 mg/kg and CYP at 25 mg/kg.
with CYP and CMN showed significant increase in reduced glu-
tathione level in all the tissues, when compared to animal treated
with CYP alone.
3.5. Effects on enzymatic antioxidant enzyme
CYP treatment significantly attenuated the CAT activity in liver,
kidney and brain tissues (Fig. 4) and CMN treatment significantly
restored the enzyme to near normal status in all the tissues. CYP
exposure resulted in significant elevation in superoxide dismutase
activity in liver, kidney and brain (Fig. 5). Simultaneous treatment
with CYP and CMN showed significant restoration in SOD level in
liver and brain but no effect on kidney tissue. The activity of glu-
tathione peroxidase was decreased in liver kidney and brain (Fig. 6).
CYP plus CMN significantly restored the activity of glutathione per-
oxidase, when compared to animals treated with CYP alone.
3.6. Histopathology
The administration of CYP for 28 days resulted in enlargement
of sinusoids space, degeneration in hepatic cords and hepatocytes
in the centrilobular areas with frequent karyomegaly and binu-
cleations (Fig. 7A) were found in the livers of the rats. After the
exposure of CYP for 28-days, tubular lining cells showed, degen-
erative necrotic changes, swollen and enlarged desquamated cells
with cytoplasmic esonophilia (Fig. 7B). In the brain engorgement of
Fig. 4. Effects of 28 days oral administration of CYP, CMN and CYP plus CMN on catalase level of liver, kidney and brain in male rats. Each bar represents mean ± SEM of 6
rats. Significant differences are indicated by superscript a: compared to control, superscript b: compared to CYP group. C: control, CMN: curcumin, CYP: cypermethrin, CMN
at 100 mg/kg and CYP at 25 mg/kg.
Fig. 5. Effects of 28 days oral administration of CYP, CMN and CYP plus CMN on
super oxide dismutase of liver, kidney and brain in male rats. Each bar represents
mean ± SEM of 6 rats. Significant differences are indicated by superscript a: com-
pared to control, superscript b: compared to CYP group. C: control, CMN: curcumin,
CYP: cypermethrin, CMN at 100 mg/kg and CYP at 25 mg/kg.
blood vessels in meninges (Fig. 7C) with increase in the perivascular
space was observed. Many neurons appeared swollen and oth-
ers vacuolated. CMN treatment showed decrease in degenerative
changes in liver, decreased the tubular degeneration and reduced
the histological alteration in brain as compared to the CYP alone
treated groups (Fig. 8A–C).
4. Discussion
In the present experiment, significant decrease in body weight
at end of the experimental period following administration of CYP
in rat has been observed. It may be attributed to the effect of insec-
ticide on gastrointestinal tract resulting in decreased appetite and
absorption of nutrients from gut (Venkateshwarlu et al., 1997) or
might be due to direct toxicity of CYP. The increased AST and ALT
activities as observed in the present study could be due to cellular
injury of the liver tissues. These observations matched with ear-
lier finding of CYP toxicity in rats (Gupta and Bhaumik, 1988) and
rabbits (Yousef et al., 2003). The increase in the activities of these
enzymes in serum is indicative for liver damage and thus causes
alteration in liver function. The present study indicated that treat-
ment with CYP caused significant increase in serum creatinine and
BUN. Similar changes in creatinine and urea values were reported in
 P. Sankar et al. / Experimental and Toxicologic Pathology 64 (2012) 487–493
Fig. 6. Effects of 28 days oral administration of CYP, CMN and CYP plus CMN on glutathione peroxidase of liver, kidney and brain in male rats. Each bar represents mean ± SEM
of 6 rats. Significant differences are indicated by superscript a: compared to control, superscript b: compared to CYP group. C: control, CMN: curcumin, CYP: cypermethrin,
CMN at 100 mg/kg and CYP at 25 mg/kg.
rabbits (Yousef et al., 2003). The elevation of serum creatinine and
BUN enzymes are considered as significant markers of renal dys-
function. Elevated blood urea is correlated either with an increased
protein catabolism in the mammalian body or from a more effi-
cient conversion of ammonia to urea as a result of increased
synthesis of enzyme involved in urea production (Rodwell, 1979).
The histopathological observations in CYP-treated rats showed the
enlargement of sinusoidal space, degeneration in hepatic cords and
hepatocytes in the centrilobular areas with frequent karyomegaly
and binucleations. Similar findings of liver damage during CYP toxi-
city have been observed earlier in rats (Yavasoglu et al., 2006). After
exposure of CYP for 28-days, tubular lining cells showed, degenera-
tive necrotic changes, swollen and enlarged desquamated cells with
cytoplasmic esonophilia (Manna et al., 2010) and in the brain, cere-
bellar and meningeal blood vessels were engorged with red blood
cells. This could be due to the accumulation of free radicals as the
consequence of increased LPO by CYP toxicity.
LPO has been extensively used as a marker of oxidative stress. In
the present study, CYP treatment produced a significant increase in
the level of MDA in the hepatic, renal and brain tissues. The increase
in the concentration of MDA is an indicator of CYP-induced LPO
leading to tissue injury. CYP exposure has been shown to cause
decrease in membrane fluidity, thereby increasing LPO (Gabbianelli
et al., 2004). Glutathione antioxidant system plays a pivotal role
in cellular defence against reactive free radicals and other oxidant
species. Hepatic GSH plays a crucial role in both scavenging reactive
oxygen species and the detoxification of xenobiotics (Haque et al.,
2003). In addition to being a direct free radical scavenger, GSH is
known to function as a substrate for glutathione peroxidase and
glutathione-S-transferase. Previous studies have shown that CYP
treatment depletes GSH levels (Kale et al., 1999) and suggested LPO
as one of the mechanisms of CYP toxicity in rats accompanied by a
concomitant decrease in cellular GSH concentration. In our study,
in CYP treated rats, levels of GSH were significantly decreased in
liver, kidney and brain.
SOD and CAT are the two enzymes that help to scavenge super-
oxide ions and hydroxyl ions, respectively. The present study
showed an increase in SOD and decrease in catalase activity in
liver, kidney and brain of CYP exposed rats. This increase could
be a consequence of the high production of superoxide anion fol-
lowing the pyrethroid treatment (Kale et al., 1999; Maiti and Kar,
1997). Similarly, increased generation of free radicals in fenvaler-
ate pyrethroid treated mice and an increased activity of SOD have
been reported (Maiti et al., 1995). CAT is a haemoprotein, which
491
reduces hydrogen peroxide to molecular oxygen and water. Fur-
thermore, it has been suggested that LPO might be a contributing
factor for decrease in the catalase activity during cypermethrin tox-
icity (Atessahin et al., 2005). Glutathione related enzymes such as
glutathione peroxidase (GPx) function either directly or indirectly
as antioxidants. In our study, there was a significant decrease in
the activities of glutathione peroxidase in liver, kidney and brain of
CYP exposed rats. GPx is non-specific for H2 O2 and a lack of sub-
strate specificity extends a range of substrates from H2 O2 to organic
hydroperoxides (Chance et al., 1979). Therefore, an excess of H2 O2
and lipid peroxides are efficiently scavenged by GPx activity. The
depression of this enzyme activity as observed in the present study
reflects perturbations in normal oxidative mechanisms during CYP
toxicity. CYP has been demonstrated to cause a significant decrease
in the activities of glutathione peroxidase in the rats (Nasuti et al.,
2003).
CMN, a phenolic compound, exhibits protective effects against
oxidative damage and it is considered to be a potent cancer chemo-
preventive agent (Duvoix et al., 2005). Rats that received CMN
along with CYP showed increase in body weight as compared
to CYP alone treated rats which indicate that CMN has appetite
inducer and anti-stress effect. This finding is in agreement with
observation of increased weight gain of rats following treatment
with CMN pretreated with arsenic (Fatma et al., 2009). The result
showed that CMN treatment prevents the elevation of serum bio-
chemical enzymes and histopathological alteration. Kalpana and
Menon (2004) suggested that CMN exerts its protective effect by
modulating the biochemical marker enzymes, LPO and augment-
ing antioxidant defense system. In the present study there was a
significant decrease in the LPO in CYP plus CMN treated group as
compared to CYP alone treated group. Treatment with CMN also
resulted in decreased LPO. These results are in agreement with pre-
vious studies (Shukla et al., 2003; Eybyl et al., 2006; Kalpana and
Menon, 2004). A protective effect of CMN has also been reported in
ex vivo experiments against cadmium and lead induced LPO in rat
brain homogenates (Daniel et al., 2004). The simultaneous treat-
ment with CMN elevated the CYP-induced decrease in the levels of
GSH. Elevation in the tissue levels of GSH by CMN as observed in
the present study is in agreement with earlier findings (Rukkumani
et al., 2004; Tirkey et al., 2005). In the present study, levels of
CAT, and GPx enzymes in liver, kidney and brain of CYP plus CMN-
treated animals were significantly increased as compared to the
CYP treatment group. It is well known that antioxidant enzymes
play an important protective role against LPO in tissues (Franesco
492 P. Sankar et al. / Experimental and Toxicologic Pathology 64 (2012) 487–493
Fig. 7. (a) Liver (CYP 25 mg/kg): diffuse and severe degeneration of hepatocytes
with distinct karyomegaly and binucleation. (b) Kidney (CYP 25 mg/kg): degener-
ative necrotic changes, swollen and enlarged desquamated cells with cytoplasmic
esonophilia. (c) Brain (CYP 25 mg/kg): engorgement of blood vessels in meninges
with increase in the perivascular space.
et al., 1985). CMN has been shown to restore the activities of SOD,
CAT and GPx during arsenic, gentamicin, ferric nitrilotriacetate and
nicotine-induced toxicity (Fatma et al., 2009; Farombi and Ekor,
2006; Venkatesan et al., 2000; Kalpana and Menon, 2004). Antioxi-
dant mechanism of CMN may include one or more of the following
interactions, scavenging or neutralizing free radicals (Soudamini
et al., 1992), interacting with oxidative cascade and preventing its
outcome (Unnikrishnan and Rao, 1992). CMN possesses distinct
structural motifs that are responsible for its antioxidant activity.
The presence of electron donating groups like phenolic hydroxyl
groups and a ␤-diketone structure is responsible for the free rad-
ical scavenging activity and inhibiting LPO (Osawa et al., 1995;
Sreejayan and Rao, 1994; Wright, 2002). In addition, CMN pri-
mary metabolite, tetrahydro curcumin, a major antioxidant with
Fig. 8. (a) Liver (CYP 25 mg/kg + CMN 100 mg/kg): hepatocytes arranged in normal
cord pattern with mild degeneration. (b) Kidney (CYP 25 mg/kg + CMN 100 mg/kg):
mild degeneration but almost normal appearance of kidney glomeruli and tubules.
(c) (CYP 25 mg/kg + CMN 100 mg/kg): almost normal appearance of brain meninges
and perivascular space.
␤-diketone moiety, exhibited antioxidant activity by cleavage of
the C–C bond at the active methylene carbon between the two
carbonyls (Pan et al., 1999). These antioxidant properties seem
to have a role in inhibiting singlet oxygen generation directly or
indirectly.
In conclusion, this study indicates that CMN has the protective
effect against CYP-induced biochemical alterations and oxidative
damage in the various organs of rats. The mechanism for this pro-
tective effect is due its free radical scavenging activity and increased
antioxidant enzymes in rats.
 P. Sankar et al. / Experimental and Toxicologic Pathology 64 (2012) 487–493
Conflict of interest
The authors declare that there are no conflicts of interest.
Acknowledgments
The Junior Research Fellowship awarded to the first author by
the Indian Council of Agricultural Research (ICAR), New Delhi is
gratefully acknowledged. The authors are thankful to the Direc-
tor, Indian Veterinary Research Institute, for providing necessary
facilities.
References
Adelsbach TL, Tjeerdema RS. Chemistry and fate of fenvalerate and esfenvalerate.
Rev Environ Contam 2003;176:136–54.
Aebi H. Catalase. In: Bergmeyer HU, editor. Methods enzymology. New York: Aca-
demic Press; 1983. p. 276–86.
Atessahin A, Yilmaz S, Karahan I, Tasdemir B. The effect of vit-E and selenium on
CYM induced oxidative stress in rats. Turk J Vet Anim Sci 2005;29:385–91.
Biswas SK, McClure D, Jimenez LA, Megson IL, Rahman I. Curcumin induces
glutathione biosynthesis and inhibits NFkappaB activation and interleukin-8
release in alveolar epithelial cells: mechanism of free radical scavenging activity.
Antioxid Redox Signal 2005;7:32–41.
Cantalamessa F. Acute toxicity of two pyrethriod; permethrin and cypermethrin in
neonatal and adult rats. Arch Toxicol 1993;67:510–3.
Cekmen M, Ilbet YO, Ozbek E, Simsek A, Ersoz C. Curcumin prevents oxida-
tive renal damage induced by acetaminophen in rats. Food Chem Toxicol
2009a;47:1480–4.
Cekmen M, Ilbey YO, Ozbek E, Simsek A, Somay A, Ersoz C. Curcumin prevents
oxidative renal damage induced by acetaminophen in rats. Food Chem Toxicol
2009b;47:1480–4.
Chance B, Sies H, Boveris A. Hydroperoxides metabolism in mammalian organ. Phys-
iol Rev 1979;59:72–7.
Daniel S, Limson JL, Dairam A, Watkins GM, Daya S. Through metal binding, cur-
cumin protects against lead- and cadmium-induced lipid peroxidation in rat
brain homogenates and against lead-induced tissue damage in rat brain. J Inorg
Biochem 2004;98:266–75.
Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F, Henry E, et al. Chemo-
preventive and therapeutic effects of curcumin. Cancer Lett 2005;223:181–90.
Eybyl V, Kotyzova D, Leseticky L, Bludovska M, Koutensky J. The influence of
curcumin and manganese complex of curcumin on cadmium-induced oxida-
tive damage and trace elements status in tissues of mice. J Appl Toxicol
2006;26:207–12.
Farombi EO, Ekor M. Curcumin attenuates gentamicin-induced renal oxidative dam-
age in rats. Food Chem Toxicol 2006;44:1443–8.
Fatma MED, Mokhtar IY, Fatma MER. Ameliorating effect of curcumin on sodium
arsenite-induced oxidative damage and lipid peroxidation in different rat
organs. Food Chem Toxicol 2009;47:249–54.
Floodstrom S, Warngard L, Lijunquist S, Ahlborg UG. Inhibition of metabolic coop-
eration in vitro and enhanced enzyme altered foci incidence in rat liver by the
pyrethroid insecticide Fenvalerate. Arch Toxicol 1988;61:218–33.
Franesco P, Silvano V, Anna M, Kevin HC, Trevor FS. Antioxidants and lipid peroxi-
dation: “In vivo” studies. Biochem Pharmacol 1985;35:397–8.
Gabbianelli R, Nasuti C, Falcioni G, Cantalamessa F. Lymphocyte DNA damage in
rats exposed to pyrethroids effect of supplementation with vitamins E and C.
Toxicology 2004;203:17–26.
Giray B, Gurbay A, Hincal F. Cypermethrin-induced oxidative stress in rat brain and
liver is prevented by Vitamin E or allopurinol. Toxicol Lett 2001;3:139–46.
Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Richardson RJ. The risk of Parkin-
son’s disease with exposure to pesticides, farming, well water and rural living.
Neurology 1998;58:1346–50.
Gupta A, Nigam D, Gupta A, Shukla GS, Agarwal AK. Effect of pyrethroid-based liquid
mosquito repellent inhalation on the blood–brain barrier function and oxidative
damage in selected organs of developing rats. J Appl Toxicol 1999;19:67–72.
Gupta PK, Bhaumik A. Pyrethroids: Their use in the control of animal ectoparasites
and impact on the environment. Adv Toxicol Environ Health 1988:71–80.
Hall BE, Vickers JA, Hopkins JA. A study to determine the bioaccumulation of 14C-
cypermethrin radioactivity in the rat following repeated oral administration.
WHO Report No. 2487-72/20; 1980.
Haque R, Bin-Hafeez B, Parvez S, Pandey S, Sayeed I, Ali M, et al. Aqueous extract
of walnut (Juglans regia L.), protects mice against cyclophosphamide-induced
biochemical toxicity. Hum Exp Toxicol 2003;22:473–80.
Joe B, Vijaykumar M, Lokesh BR. Biological properties of curcumin cellular and
molecular mechanisms of action. Crit Rev Food Sci Nutr 2004;44:97–111.
Kale M, Rathore N, John S, Bhatnagar D. Lipid peroxidative damage on pyrethroid
exposure and alterations in antioxidant status in rat erythrocyte: a possible
involvement of reactive oxygen species. Toxicol Lett 1999;105:197–205.
Kalpana C, Menon VP. Curcumin ameliorates oxidative stress during nicotine-
induced lung toxicity in Wistar rats. Ital J Biochem 2004;53:82–6.
493
Klimek J. Cytochrome P-450 involvement in the NADPHdependent lipid
peroxidation in human placental mitochondria. Biochim Biophys Acta
1990;1044:158–64.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with Folin-
Phenol reagent. J Biol Chem 1951;193:265–75.
Luna LG. Manual of histologic staining methods of the Armed Forces Institute of
Pathology. 3rd ed. Mc.Graw Hill; 1968.
Madesh J, Balasubramanian KA. Microtitre plate assay for superoxide dismu-
tase using MTT reduction by superoxide. Indian J Biochem Biophys 1998;35:
184–8.
Maheshwari RK, Singh KA, Gaddipati J, Srimal CR. Multiple biological activity of
curcumin: a short review. Life Sci 2006;78:2081–7.
Maiti PK, Kar A. Dimethoate inhibits extrathyroidal 5′ -monodeiodination of thy-
roxine to 3,3′ ,5-triiodothyronine in mice: the possible involvement of the lipid
peroxidative process. Toxicol Lett 1997;91:1–6.
Maiti PK, Kar A, Gupta P, Chaurasia SS. Loss of membrane integrity and inhibition
of type-I iodothyronine 5′ -monodeiodinase activity by fenvalerate in female
mouse. Biochem Biophys Res Commun 1995;214:905–9.
Manikandan P, Sumitra M, Aishwarya S, Manoharb BM, Lokanadamc B, Puvanakr-
ishnan R. Curcumin modulates free radical quenching in myocardial ischaemia
in rats. J Biochem Cell Biol 2004;36:1967–80.
Manna S, Bhattacharyya D, Mandal TK, Das S. Repeated dose toxicity of alfa-
cypermethrin in rats. J Vet Sci 2004;5:241–5.
Manna S, Bhattacharyya D, Basak K, Mandal TK. Single oral dose toxicity study of
alfa-cypermethrin in rats. Indian J Pharmacol 2010:25–8.
Michelangeli F, Robson MJ, East JM, Lee AG. The conformation of pyrethroids bound
to lipid bilayers. Biochim Biophys Acta 1990;1028:49–57.
Nandi P, Talukder G, Sharma A. Dietary factor in cancer chemoprevention. The
Nucleus 1997;40:128–44.
Nasuti C, Franco C, Giancarlo F, Rosita G. Different effects of type I and type II
pyrethroids on erythrocyte plasma membrane properties and enzymatic activity
in rats. Toxicology 2003;191:233–44.
Osawa T, Sugiyama Y, Inayoshi M, Kawakishi S. Antioxidant activity of tetrahy-
drocurcuminoids. Biosci Biotechnol Biochem 1995;59:1609–12.
Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization
of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70:158–69.
Pan M, Huang T, Lin J. Biotransformation of curcumin through reduction and glu-
curonidation in mice. Drug Metab Dispos 1999;27:486–94.
Prasanth KM, Rajini PS. Fenvalerate-induced oxidative damage in rat tissues and its
attenuation by dietary seasame oil. Food Chem Toxicol 2005;43:299–306.
Reddy AC, Lokesh BR. Studies on the inhibitory effects of curcumin and eugenol on
the formation of reactive oxygen species and the oxidation of ferrous ion. Mol
Cell Biochem 1994;137:1–8.
Rodwell EW. Review of physiological chemistry. 17th ed. California: Lange Medical
Publications; 1979. p. 401–4.
Rukkumani R, Aruna K, Verma PS, Rajasekaran KN, Menon VP. Comparative effects
of curcumin and an analog of curcumin on alcohol and PUFA induced oxidative
stress. J Pharmacol Sci 2004;7:274–83.
Sedlak J, Lindsay RH. Estimation of total, protein-bound and nonprotein sulfydryl
groups in tissue with Ellman’s reagent. Anal Biochem 1968;25:192–205.
Shafiq-u-Rehman S, Chandra O, Abdulla M. Evaluation of malondialdehyde as an
index of lead damage in rat brain homogenates. Biometals 1984;8:192–205.
Shukla Y, Annu A, Taneja P. Antigenotoxic potential of certain dietary constituents.
Teratog Carcinog Mutagen 2003;1:325–35.
Soudamini KK, Unnikrishnan MC, Soni KB, Kuttan R. Inhibition of lipid peroxida-
tion and cholesterol levels in mice by curcumin. Indian J Physiol Pharmacol
1992;36:239–43.
Sreejayan N, Rao MN. Curcuminoids as potent inhibitors of lipid peroxidation. J
Pharm Pharmacol 1994;46:1013–6.
Tirkey N, Kaur G, Vij G, Chopra K. Curcumin, a diferuloylmethane, attenuates
cyclosporine-induced renal dysfunction and oxidative stress in rat kidneys. BMC
Pharmacol 2005;5:15–23.
Unnikrishnan MK, Rao MNA. Curcumin prevents nitrite induced methhaemoglobin
formation. FEBS 1992;301:195–6.
Venkatesan N, Punithavathi D, Arumugan V. Curcumin prevents adriamycin nephro-
toxicity in rats. Br J Pharmacol 2000;12:231–4.
Venkatesan N. Pulmonary protective effects of curcumin against paraquat toxicity.
Life Sci 2000;66:21–8.
Venkateshwarlu P, Sharma BJR, Kalakumar B, Reddy KS, Ravikumar P. Comparative
evaluation of toxicity of carbaryl, cypermethrin and malathion of testis in mice.
Indian J Toxicol 1997;4:33–7.
Wright JS. Predicting the antioxidant activity of curcumin and curcuminoids. J Mol
Struct 2002;591:207–17.
Yavasoglu A, Sayam F, Uyanikgil Y, Turgut M, Yavasoglu NU. The cypermethrin
induced biochemical and histological alterations in rat liver. J Health Sci
2006;52:774–80.
Yousef MI, Demerdash FM, Kamei KI, Salhen KS. Changes in some hematological
and biochemical indices of rabbits induced by isoflavones and cypermethrin.
Toxicology 2003;189:223–34.
Zegura B, Lah TT, Filipic M. The role of reactive oxygen species in microcystin-LR-
induced DNA damage. Toxicology 2004;200:59–68.
Zini R, Lamirande E, Gagnon G. Reactive oxygen species in semen of infertile patients.
Levels of superoxide dismutase and catalase like activities in animal plasma and
spermatozoa. J Androl 1993;16:183–8.