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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). Summary 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. Summary 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. |