EFFECT OF DIETARY ANTIOXIDANTS ON DIELDRIN-INDUCED HEPATOTOXICITY IN MICE

An increasing number of reports suggest that oxidative stress plays a role in the toxicity of various xenobiotics, including organochlorine pesticides and drugs such as phenobarbital. Antioxidants appear to be protective against the damage induced by an acute dose of endrin, supp orting the theory of a role for reactive oxygen in the toxicity of thi s class of compounds. The current study examined the effects of the di etary administration of vitamin C (400 mg/kg diet) or vitamin E (200 m g DL-alpha-tocopherol acetate/kg diet) on hepatotoxicity induced by su bchronic (7 or 28 days) feeding of dieldrin (1, 3 and 10 mg/kg diet) t o male B6C3F(1) mice, Hepatoxicity induced by feeding of dieldrin for 28 days was evidenced by liver enlargement, hypertrophy of centrolobul ar hepatocytes, induction of hepatic ethoxyresorufin O-deethylase acti vity, and increased DNA synthesis in hepatocytes, particularly in cent rolobular hepatocytes, Neither vitamin inhibited the dose-dependent in crease in liver/body weight ratios, hypertrophy of centrolobular hepat ocytes, or induction of hepatic ethoxyresorufin O-deethylase. Vitamin E, however, inhibited hepatic DNA synthesis at all dietary intakes of dieldrin, while vitamin C was inhibitory at 1 and 3, but stimulatory a t 10 mg dieldrin per kg diet, The major changes in DNA labeling occurr ed in the centrolobular zones, but were not consistently inhibited by vitamins C or E, The ability of antioxidant vitamins to inhibit dieldr in-induced hepatic DNA synthesis suggests oxidative stress is involved in the toxicity of this compound; however, the inability of these vit amins to prevent all hepatotoxic changes indicates other factors are a lso involved.