Improvement of Phase I Drug Metabolism with Schisandra chinensis Against CCl₄ Hepatotoxicity in a Rat Model

 

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Abstract

The seed extract of Schisandra chinensis was investigated in the rat for its restorative or therapeutic effect on Phase I hepatic drug metabolism following intoxication by carbon tetrachloride (CCl₄). Male Sprague Dawley rats (220 - 250 g) were divided into two sets, one included rats with or without CCl₄ intoxication, the other included CCl₄ intoxicated rats with or without treatment of Schisandra extract. With the treatment regimen, rats received four oral doses of Schisandra (160 mg/kg) or the same volume of water at 8, 24, 32 and 48 h after CCl₄ intoxication. A single oral dose (80 mg/kg) of antipyrine, a conventional probe for oxidative drug metabolism, was then administered. The levels of liver serum transaminases and cytochrome P₄₅₀ were measured and the pharmacokinetics of antipyrine were assessed using a non-compartmental approach via WinNonlin. In comparison to the rats without CCl₄ intoxication (t_1/2: 2.2 ± 0.9 h; Cl/F: 0.30 ± 0.01 L/h/Kg; P₄₅₀: 0.611 ± 0.190 nmol/mg protein), CCl₄ administration significantly decreased elimination (t_1/2: 12.0 ± 3.9 h) and oral clearance (Cl/F: 0.049 ± 0.018 L/h/kg) of antipyrine, and markedly reduced the content of P₄₅₀ (0.075 ± 0.011 nmol/mg protein). Data obtained from intoxicated animals treated by Schisandra extract, compared to those without treatment, showed significant (p < 0.05) improvement in the t_1/2 (4.45 ± 1.7 h) and Cl/F (0.096 ± 0.018 ml/h) estimates of antipyrine and a 2 - 3 fold increase in P₄₅₀ level (0.190 ± 0.072 nmol/mg protein). Findings in this study suggest that the seed extract of Schisandra appeared to be a promising agent for the improvement of Phase I oxidative metabolism in the liver damaged by CCl₄.

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D. Ph. Ronald C. Li

Pharmacokinetic/Pharmacodynamic Sciences

Genetics Institute

One Burtt Road

Andover

MA 01810

USA

Email: rcli@genetics.com

Phone: 1-978-247-1389