The administration of carbon tetrachloride (CCl(4)) to mice produced hepatotoxicity, showing a significant increase in the serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST). Mice pretreated with Jiang-Zhi-Li-Gan (JZLG, 100-900 mg/kg, p.o.), a domestic remedy for liver disease in Rui-Jin Hospital, showed a significant decrease in serum ALT and AST levels when compared to the group treated with CCl(4) alone. The standard drug, bifendate (200 mg/kg, p.o.), also exhibited similar results. In the acute toxicity study, JZLG did not show any mortality up to a dose of 32 g/kg body weight. Based on the results obtained, it can be concluded that JZLG seems to possess hepatoprotective activity in mice. These results support the use of this prescription against chemical hepatic injury.
Hepatic injury induced by oxaliplatin has been reported. Even though agents are available that reduce oxaliplatin-induced hepatocyte toxicity, their mode of action has remained obscure. In the present study, hepatic L02 cells were incubated with different combinations of oxaliplatin and carbocisteine. Signifi cantly increased levels of reactive oxygen species (ROS) were found in L02 cells treated with oxaliplatin. Using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) as an indicator of cell viability and fl ow cytometry, we found that carbocisteine could reverse oxaliplatin-induced apoptosis of L02 cells. Western blot analysis demonstrated that oxaliplatin could induce apoptosis of L02 cells by reducing the Bcl-2/Bim ratio, stimulating the cytochrome c release, and activating caspase-3. All of these effects could be suppressed by carbocisteine. We further found that carbocisteine did not affect the anticancer effect of oxaliplatin against HT-29 cells. This is the fi rst report opening prospects for the clinical use of carbocisteine in the pretreatment against liver injury accompanying the chemotherapy regimen with oxaliplatin.
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