Protective effects of Ganoderma lucidum spore on cadmium hepatotoxicity in mice

The medicinal fungus Ganoderma lucidum has been shown to have hepatoprotective effects. G. lucidum contains triterpenes and polysaccharides, and the Sporoderm-broken G. lucidum powder is particular beneficial. This study utilized G. lucidum spore to examine its effect on [Cd(II)]-induced hepatotoxicity in mice and the mechanism of the protection. Mice were pretreated with G. lucidum spore (0.1, 0.5, and 1.0 g/kg, po, for 7 days), and subsequently challenged with a hepatotoxic dose of Cd(II) (3.7 mg/kg, ip). Liver injury was evaluated 8h later. G. lucidum spore protected against Cd(II)-induced liver injury in a dose-dependent manner, as evidenced by serum alanine aminotransferase, aspartate aminotransferase and histopathology. To examine the mechanism of protection, subcellular distribution of Cd(II) was determined. G. lucidum spore decreased Cd(II) accumulation in hepatic nuclei, mitochondria, and microsomes, but increased Cd(II) distribution to the cytosol, where Cd(II) is sequestered by metallothionein, a protein against Cd(II) toxicity. Indeed, G. lucidum spore induced hepatic metallothionein-1 mRNA 8-fold, and also increased metallothionein protein as determined by the Cd(II)/hemoglobin assay. Cd(II)-induced oxidative stress was also decreased by G. lucidum spore, as evidenced by decreased formation of malondialdehyde. In summary, G. lucidum spore is effective in protection against Cd(II)-induced hepatotoxicity, and this effect is due, at least in part, to the induction of hepatic metallothionein to achieve beneficial effects.