THE PROTECTIVE EFFECTS OF EUGENOL ON CARBON-TETRACHLORIDE INDUCED HEPATOTOXICITY IN RATS

Our earlier studies in vitro have shown that eugenol inhibits liver mi crosomal monooxygenase activities and carbon tetrachloride (CCl4)-indu ced lipid peroxidation (Free Rad. Res. 20, 253-266, 1994). The objecti ve of the present investigation was to study the ill vivo protective e ffect of eugenol against CCl4 toxicity. Eugenol (5 or 25 mg/kg body wt ) given orally for 3 consecutive days did not alter the levels of seru m glutamic oxalacetic transaminase (SGOT), microsomal enzymes such as cytochrome P-450 reductase, glucose-6-phosphatase (G-6-Pase) xenobioti c-metabolizing enzymes (aminopyrine N-demethylase, N-nitrosodimethylam ine-demethylase and ethoxyresorufin-O-deethylase) and liver histology. Doses of eugenol (5 or 25 mg/kg) administered intragastrically to eac h rat on three consecutive days i.e. 48 hr, 24 hr and 30 min before a single oral dose of CCl4 (2.5 ml/kg body wt) prevented the rise in SGO T level without appreciable improvement in morphological changes in li ver. Eugenol pretreatment also did not influence the decrease in micro somal cytochrome P-450 content, G-6-Pase and xenobiotic-metabolizing e nzymes brought about by CCl4. Since eugenol is metabolized and cleared rapidly from the body, the dose schedule was modified in another expe riment, Eugenol (0.2, 1.0, 5.0 or 25 mg/kg) when given thrice orally i .e. prior to (-1 hr) along with (0 hr) and after (+3 hr) the i.p. admi nistration of CCl4 (0.4 ml/kg) prevented significantly the rise in SGO T activity as well as liver necrosis. The protective effect was more e vident at 1 mg and 5 mg eugenol doses. However, the decrease in micros omal G-6-Pase activity by CCl4 treatment was not prevented by eugenol suggesting that the damage to endoplasmic reticulum is not protected. The protective effect of eugenol against CCl4 induced hepatotoxicity i s more evident when it is given concurrently or soon after rather than much before CCl4 treatment.