Protective effects of Pycnogenol^® on carbon tetrachloride-induced hepatotoxicity in Sprague-Dawley rats

Oxidative damage is implicated in the pathogenesis of various liver injuries. In the present study the ability of Pycnogenol^® (PYC) as an antioxidant to protect against CCl₄-induced oxidative stress and hepatotoxicity in rats was investigated. Four experimental groups of six rats each were constructed: a vehicle control group received the respective vehicles (distilled water and corn oil) only; a CCl₄ group received a 14-day repeated intraperitoneal (i.p.) dose of distilled water and then a single oral dose of CCl₄ at 1.25 ml/kg; and the CCl₄&PYC 10 and CCl₄&PYC 20 groups received a 14-day repeated i.p. dose of PYC 10 and 20 mg/kg, respectively, and then a single oral dose of CCl₄ at 1.25 ml/kg. Hepatotoxicity was assessed 24 h after the CCl₄ treatment by measurement of serum aminotransferase (AST) and alanine aminotransferase (ALT) activities, hepatic malondialdehyde (MDA) and glutathione (GSH) concentrations, and catalase, superoxide dismutase (SOD), and glutathione-S-transferase (GST) activities. The results were confirmed histopathologically. The single oral dose of CCl₄ produced significantly elevated levels of serum AST and ALT activities. Histopathological examinations showed extensive liver injuries, characterized by extensive hepatocellular degeneration/necrosis, fatty changes, inflammatory cell infiltration, congestion, and sinusoidal dilatation. In addition, an increased MDA concentration and decreased GSH, catalase, SOD, and GST were observed in the hepatic tissues. On the contrary, PYC treatment prior to the administration of CCl₄ significantly prevented the CCl₄-induced hepatotoxicity, including the elevation of serum AST and ALT activities and histopathological hepatic lesions, in a dose-dependent manner. Moreover, MDA and GSH levels and catalase, SOD, and GST activities in hepatic tissues were not affected by administration of CCl₄, indicating that the pretreatment of PYC efficiently protects against CCl₄-induced oxidative damage in rats. The results indicate that PYC has a protective effect against acute hepatotoxicity induced by the administration of CCl₄ in rats, and that the hepatoprotective effects of PYC may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity.