Effect of Zinc on Hepatic Drug Metabolism under Ethanol Toxicity

The effects of zinc on drug-metabolizing enzymes in the liver were examined in male Wistar rats following ethanol intoxication. Rats were orally fed 3 mL of 30% ethanol daily for either two, four, or eight weeks and were orally administered zinc sulfate (ZnSO4.7H2O) at a dose level of 227 mg/L. Levels of reduced glutathione (GSH) and the activities of cytochrome P-450, cytochrome b(5), NADPH cytochrome-C-reductase and glutathione-S-transferase (GST) were determined in liver after two, four, and eight weeks. Significant elevation was observed in the activities of the enzymes of the mixed function oxidase system in response to toxicity induced by ethanol at all the intervals. These effects of were ascribed to the enhanced activity of the microsomal ethanol oxidizing system and the associated increase in reactive oxygen species production. Zinc supplementation to these ethanol-intoxicated animals resulted in normalization of these elevated values significantly, but still they do not attain normal levels. Significant increase was observed in reduced glutathione content in animals after four and eight weeks of ethanol feeding, which appeared to be further elevated in combined zinc and ethanol treatment. Significant elevation in the activity of GST was illustrated on ethanol-fed animals at all the three treatment intervals. Furthermore, the activity of this enzyme was only moderately normalized following zinc treatment. This was accredited to the antioxidant potential of zinc, as well as its ability to induce metallothionein content, which provide protection against the toxic effects of ethanol. To conclude, zinc was able to normalize the effects of ethanol in the liver.