16. Antioxidant activity of Ganoderma lucidum: Protective effects on carbon tetrachloride-induced hepatotoxicity.

P.C. Ng, Y.C. Kong, K.M. Ko, C.M. So, P.K. Yick

Ganoderma lucidum (Lingzhi) stands for the symbol of longevity in traditional Chinese medicine. In light of the oxidative stress hypothesis of aging, we have examined the effects of Lingzhi pretreatment orally on carbon tetrachloride (CCl4)-induced hepatotoxicity in rats, with an endeavor to identify the anti-aging principle. In the present study, female Sprague Dawley rats (200–300 g), with or without Lingzhi pretreatment, were administered orally with CCl4 at a dose of 1 ml/kg, and the extent of hepatotoxicity was assessed by measuring the antioxidant capacity of hepatic tissue homogenates and the activity of plasma alanine aminotransferase (ALT) 24 hours post-dosing. In CCl4-treated control animals (i.e. without Lingzhi pretreatment), a significant impairment in hepatic antioxidant status was observed following CCl4 administration, as evidenced by the decrease in hepatic reduced glutathione (GSH) content, increases in the sensitivity of hepatic tissue homogenates to GSH depletion and the formation of thiobarbituric acid-reactive substances induced by in vitro oxidative challenge, and decreases in the activity of glutathione reductase (GRD) and Cu,Zn-superoxide dismutase (Cu,Zn-SOD). These antioxidant-related hepatic alterations were associated with an increase in plasma ALT activities, indicating hepatocellular damage. Pretreating rats with increasing doses (3 or 6 daily doses of 200 mg/kg prior to CCl4 treatment) of water-soluble extract prepared from Lingzhi markedly protected against the CCl4-induced depression in hepatic antioxidant status, as well as elevation in plasma ALT activity. In animals pretreated with 6 doses of Lingzhi, the CCl4-induced increase in susceptibility of hepatic GSH to in vitro peroxide-induced depletion was greatly reduced, with values of GSH content being even higher than those of the controls (those without CCl4 treatment). However, activities of GRD and Cu, Zn-SOD were not significantly increased by Lingzhi pretreatment. The ensemble of results suggests that the hepatoprotection afforded by Lingzhi pretreatment may be attributed to its antioxidant activity.