Perchloroethylene-induced alterations in glucose metabolism and their prevention by 2-deoxy-D-glucose and vitamin E in mice

The effect of 2-deoxy-D-glucose (2DG) and vitamin E on the alterations in glucose metabolism induced by perchloroethylene (PER) was studied in mice. Oral administration of PER (3 g kg-1 body wt. day-1) in sesame oil for 15 days caused a significant increase in liver weight, degeneration/necrosis of hepatocytes and increase in kidney weight, glomerular nephrosis and degeneration. These changes occurred concurrently with a significant decrease in blood glucose level, elevated activities of hexokinase, aldolase and phosphoglucoisomerase and decreased activity of gluconeogenic enzymes (glucose-6-phosphatase and fructose-1,6-diphosphatase), indicating the sensitivity of liver and kidney as target tissues in PER toxicity. Evidence is presented that both 2DG (500 mg kg-1 body wt. day-1 i.p.) and vitamin E (400 mg kg-1 body wt. day-1 by oral gavage) during concomitant administration prevented most of the above PER-induced biochemical and pathological alterations. These results suggest that early metabolic and pathological perturbations following exposure of PER in mice can provide the basis for its documented potential for chronic effects like cytotoxicity and may be involved in modulation of carcinogenicity.