الفهرس 
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Abstract
The aim of the present study was promotion effects of permethrin(PM) or cypermethrin (CM) for inducing carcinogenicity with 2-
acetylaminofluorene (2-AAF) in male albino rats in two folds; oxidative
stress and antioxidant defense dysfunction as well as L-C protective role
against these effects.
Pyrethroid insecticides, PM and CM are used on a large scale in many
agricultural protection programs and may cause hazards for animal and
human health.
Changes in liver function biomarkers; serum alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) were
estimated. Also, liver 5’-nucleotidase (5’-NT) enzyme was evaluated.
Various anti-oxidants; reduced glutathione (GSH), glutathione-stransferase
(GST), glutathione reductase (GR), glutathione peroxidase
(GPx), catalase (CAT) and superoxide dismutase (SOD) enzymes were
also estimated. On the other hand, oxidative stress markers; xanthine
oxidase (XO), lipid peroxidation (LPO), total sialic acid (TSA) and
advanced oxidation protein products (AOPPs) were evaluated in treated
animals. In addition, total DNA and RNA contents were estimated.
The experimental protocol involves three main experiments:
Experiment I: which deals with the comparison of hepatotoxicity of
permethrin (PM) and cypermethrin (CM) and evaluates which one of
them is stronger as an inducer for oxidative stress and antioxidant
dysfunction. Experimental animals were divided into three groups, each
group consisting of 7 rats and classified as follows:
Group I: control rats received corn oil (2 ml/kg b. w., orally/ day, for 30
days).
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174
Group II: rats received permethrin (20.83 mg/kg b. w., orally/ day, for 30
days).
Group II: rats received cypermethrin (8.33 mg/kg b. w., orally/ day, for
30 days). The data obtained can be summarized as follows:
The oral administration of both pyrethroids caused a highly
significant elevation in serum ALT and AST activities. On contrary, liver
5’-NT enzyme activity was significantly reduced with PM and CM
intoxication.
Various anti-oxidants; GSH, GPx, GR, CAT and SOD recorded
highly significant (P < 0.001) reductions with both PM and CM
treatment. In contrast, GST enzyme showed highly significant increase
with PM and CM treatment.
On the other hand, oxidative stress markers; liver xanthine oxidase
(XO), lipid peroxidation (LPO), total sialic acid (TSA) and serum
advanced oxidation protein products (AOPPs) elevated in treated animals
with PM or CM. Also, liver DNA and RNA contents were slightly
affected by PM or CM. In general, it is clear from our data that, CM is
more effective than PM. This may be expected with considering the
presence of an alpha-cyno substituent in CM structure which can
potentaite its toxicity.
Experiment II: The aim of this experiment was to evaluate the protective
effect of L-carnitine (L-C) against hepatotoxicity of permethrin (PM) in
combination with 2-acetylaminofluorene (2-AAF). 80 Male albino rats
were divided into four groups, 20 rats each.
Group I: as control, received corn oil (2ml/kg b.wt. orally /day) for 8
weeks.
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175
Group II: received 1/60 LD50 PM (20.83 mg/kg b.w., orally/day) for 8
weeks.
Group III: received 2-AAF (75 mg/kg b.w. i.p. /day, for one week before
PM administration), with the same manner as in group II.
Group IV: Rats received L-C for two weeks, as a pre treatment
(200mg/kg b.w., orally/ day, for two weeks), 1st week before 2-AAF and
2nd week along with 2-AAF, then treated with PM (with the same doses as
in grs. II and III). Biochemical analyses were throughout a follow up
period 1, 2, 4 and 8 weeks from the beginning of PM treatment.
Serum ALT and AST recorded gradual significant elevations (P <
0.001) with PM and (2-AAF+PM) treatments, throughout the follow up
period, with order 2-AAF +PM > PM, when compared to control rats. In
contrast, a reduction for liver 5’-NT, GSH, GR, GPx, SOD and CAT
activities, was gradually produced throughout the follow up period. Liver
DNA and RNA contents were slightly affected by PM, whereas 2-AAF
enhanced PM toxicity and elevated DNA and RNA levels. Pretreatment
of L-C reduced the all induced alterations of PM and 2-AAF+ PM
significantly (p< 0.001), with stage dependant manner, through the follow
up period. On the other side, treatment of rats with PM or (2-AAF+ PM)
caused a notable increases in liver GST and XO enzymes. Similarly, liver
LPO, liver TSA and serum AOPPs were elevated, when compared to
control group. Pretreatment of L-C markedly reduced the elevation in
these levels but values still high when compared to their control group.
Experiment III: The aim of this experiment was to evaluate the
protective effect of L-carnitine (L-C) against hepatotoxicity of
Summary
176
cypermethrin (CM) in combination with 2-acetylaminofluorene (2-AAF).
80 Male albino rats were divided into four groups, 20 rats each.
Group I: as control, received corn oil (2ml/kg b.w., orally /day) for 8
weeks.
Group II: received 1/60 LD50 CM (8.33mg/kg b.w., orally/day) for 8
weeks.
Group III: received 2-AAF (75 mg/kg b.w., i.p. /day, for one week before
CM administration), with the same manner as in group II.
Group IV: Rats received L-C for two weeks, as a pretreatment (200mg/kg
b.w., orally/ day, for two weeks), 1st week before 2-AAF and 2nd week
along with 2-AAF, then treated with CM (with the same doses as in grs.
II and III). Biochemical analyses were throughout a follow up period 1,
2, 4 and 8 weeks from the beginning of CM treatment.
Serum ALT and AST activities recorded gradual significant
elevations (P < 0.001) with CM and (2-AAF+CM) treatments, throughout
the follow up period, with order 2-AAF +CM > CM, when compared to
control rats. In contrast, a reduction in liver 5’-NT, GSH, GR, GPx, SOD
and CAT activities, was gradually produced throughout the follow up
period. Pretreatment of L-C reduced the all induced alterations of CM and
2-AAF+ CM significantly (p< 0.001), with time-dependant manner,
through the follow up period. On the other side, treatment of rats with
CM or (2-AAF+ CM) caused significant elevations in liver GST and XO
enzymes. Also, liver LPO, liver TSA and serum AOPPs levels were
increased when compared to control groups. On the other hand, liver
DNA and RNA contents were elevated with 2-AAF pretreatment to CM.
Pretreatment of L-C markedly ameliorated these levels but values are still
far from control group.