الفهرس 
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Abstract
The present study was carried out to investigate the role of cytochrome P450 isozymes (CYP450) in oxidative stress in normolipidemic and hyperlipdemic rats. Phenobarbitone sodium (PB) was used as an inducer of CYP450 and cobalt chloride (CoCl2) was used as an inhibitor of CYP450. The possible protective effect of vit.C against oxidative damage was evaluated.
In the first set of our experiments, the effect of PB (80 mg/kg, i.p) on oxidative stress parameters and serum lipid profile in normolipidemic rats was evaluated. The results clearly demonstrated that the i.p injection of PB (80 mg/kg) for two subsequent days caused significant reduction in plasma SOD, CAT , GR, GPX and GSH and significant increase in plasma MDA , H2O2 and serum TGS without significant change in plasma NO, serum cholesterol, HDL or LDL compared to the control group. Our histopathological results revealed that PB induced liver and kidney damage.
In hyperlipidemic rats, the results showed that the i.p injection of PB (80 mg/kg) was found to increase plasma NO significantly. Similarly, there was significant reduction in plasma SOD, CAT, GR, GPX and GSH and significant increase in plasma MDA, H2O2. No significant alteration in serum cholesterol, TGS, HDL or LDL.
Treatment of normolipidemic rats with CoCl2 ( 60 mg/kg, sc ) for two subsequent days produced significant decrease in plasma SOD, CAT and GR , but did not induce significant change in plasma level of NO, GPX, GSH or H2O2. It increased lipid peroxidation as evidenced by a highly significant increase in plasma MDA as compared to the control group. Our results revealed that s.c injection of CoCl2 (60 mg/kg) for 2 subsequent days caused significant increase in serum cholesterol and LDL without significant alteration in serum HDL or TGS compared to the control group. Histopathological examination of the liver and kidney showed mild damage.
In hyperlipidemic rats, changes in plasma oxidative stress parameters and serum lipid profiles were studied in CoCl2-treated rats. The results showed that CoCl2 (60 mg/kg.sc) induced significant decrease in plasma SOD, CAT and GSH. Plasma MDA and NO were significantly increased. No significant alterations in plasma GR, GPX or H2O2 were recorded. Serum lipids did not significantly change. Our pathological results revealed mild liver and kidney damage.
It is of interest that, vit.C by itself did not induce structural disturbances in both rat liver and kidney in this study.
Results of this investigation led to the following conclusions:-
1- Both microsomal enzyme inducer (PB) and microsomal enzyme inhibitor (CoCl2) induced oxidative stress in normolipidemic and hyperlipidemic rats.
2- Pretreatment with vit.C (250 mg/kg, i.p) to PB-treated rats and to CoCl2-treated rats decreased the oxidative damage in both normolipidemic and hyperlipidemic rats as assessed by biochemical measurements and histopathological examination.