Chlorpyrifos-induced alterations in the activities of carbohydrate metabolizing enzymes in rat liver: the role of zinc.

The present study was conducted to evaluate the adverse effects of chlorpyrifos on the key enzymes of carbohydrate metabolism in liver, and also to assess the role of zinc under these toxic conditions. Male Sprague-Dawley (SD) rats received either oral chlorpyrifos treatment (13.5 mg/kg body weight in corn oil) every alternate day, zinc alone (227 mg/l in drinking water), or combined chlorpyrifos and zinc treatments for a total duration of 8 weeks. The effects of different treatment regimens were studied on various enzymes of carbohydrate metabolism in the rat livers, which included hexokinase, glucose-6-phosphatase, fructose-1,6-diphosphatase, glycogen phosphorylase, succinate dehydrogenase (SDH), lactate dehydrogenase (LDH) and the levels of glycogen. In vitro uptake of (14)C-D-glucose was also assessed in liver slices after similar treatments. Chlorpyrifos intoxication resulted in a significant increase in the activities of glucose-6-phosphatase and glycogen phosphorylase, whereas, it caused a significant inhibition in the levels of hexokinase, SDH, LDH and glycogen content. However, zinc treatment to chlorpyrifos-intoxicated animals was able to normalize the activities of most of these enzymes to either close to, or within normal limits. Chlorpyrifos intoxication demonstrated significantly inhibited (14)C-D-glucose uptake in liver slices, which again was reversed to normal limits following simultaneous zinc treatment. Levels of metallothionein were also found to be depressed in chlorpyrifos-treated animals, but tended to increase significantly on co-administration of zinc to chlorpyrifos-treated group. Hence, the present study clearly suggests that zinc plays an important role in regulating the hepatic activities of the enzymes involved in carbohydrate metabolism under conditions of chlorpyrifos toxicity.