Emodin reverses CCl4 induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural changes: The in vivo evidence

Abstract

The curative effect of emodin (1,3,8-trihydroxy-6-methyl anthraquinone), an active compound of the plant species Ventilago maderaspatana Gaertn, was evaluated against carbon tetrachloride (CCl(4)) induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural alterations in rats. Female rats were administered CCl(4) (1.5 mL/kg, ip) followed by varying doses of emodin (20, 30 and 40 mg/kg, oral po) after 24 h of CCl(4) administration. Animals were euthanized after 24 h of last administration to determine liver function tests in serum, hepatic light microscopic and ultrastructural changes, activity of CYP enzymes, microsomal lipid peroxidation and protein contents, hexobarbitone induced sleep time and bromosulphalein retention. The CCl(4) induced-toxic effects were observed with sharp elevation in the release of serum transaminases, alkaline phosphatase, lactate dehydrogenase and gamma-glutamyl transpeptidase. An initial study for an optimum dose of emodin among different dose levels revealed that a 30 mg/kg dose was effective in restoring all the enzymatic variables and liver histoarchitecture in a dose dependent manner. Exposure to CCl(4) diminished the activities of CYP enzymes (i.e. aniline hydroxylase and amidopyrine-N-demethylase and microsomal protein contents with concomitant increase in microsomal lipid peroxidation). Emodin at 30 mg/kg effectively reversed the CCl(4) induced hepatotoxic events, which was consistent with ultrastructural observations. Hexobarbitone-induced sleep time and plasma bromosulphalein retention also improved liver functions after emodin therapy. By reversal CYP activity and ultrastructural changes, emodin shows a strong hepatoprotective abilities.