Protective effects of alpha-lipoic acid against benzene induced toxicity in experimental rats

M.M. El Batsh, S.S. Zakaria, H.H. Gaballah

Department of Clinical Pharmacology, Faculty of Medicine, Menoufia University, Egypt. maha.ali@med.menofia.edu.eg

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• Pharmacology

OBJECTIVE: The aim of the present study was to examine the potential protective effects of Alpha-Lipoic Acid (ALA) against benzene induced alteration in CYP2E1 gene function, DNA damage as well as the oxidant-antioxidant status.

MATERIALS AND METHODS: Fifty adult male Wister rats were used for this study. Rats were randomized and divided into four groups: Group I was designated as control group and received a vehicle of olive oil; Group II was received alpha lipoic acid in a dose of (20 mg/kg, i.p.); Group III received only I.M. injection of benzene in a dose of 2 ml/kg. Group IV received both alpha lipoic acid in a dose of (20 mg/kg, i.p.) and I.M. injection of benzene in a dose of 2 ml/kg. The animals were treated on each alternate day for 30 days then all rats were sacrificed and both blood and liver tissue samples were taken to measure serum malondialdehyde (MDA) Level; serum level of reduced glutathione (GSH); level of serum 8-hydroxy-2’-deoxyguanosine; hepatic microsomal cytochrome P450 2E1 activity and gene expression.

RESULTS: Benzene significantly increased serum malondialdehyde (MDA), 8-hydroxy-2’-deoxyguanosine (8-OHdG) and both CYP2E1 activity and gene expression but significantly decreased level of reduced glutathione (GSH). These changes are reversed upon administration of ALA.

CONCLUSIONS: The current study provided evidence that the linkage between CYP2E1-dependent oxidative stress, DNA damage, and GSH homeostasis could contribute to the toxic actions of benzene which can be counteracted by ALA by its suppression action on CYP2E1, inhibition of lipid peroxidation and oxidative DNA damage as well as maintenance of intracellular antioxidants status.

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