Interventional effect of osthol on experimental liver injury in mice / 中国组织工程研究

ABSTRACT

BACKGROUND: Osthol is a simple coumarin from Cnidium monnier (L.)Cusson which has been long used of in China as a herbal medicine for arthritis. We have previously observed protective effects of osthol on Ca2+antagonism, oxidative stress and inflammation. And other researches reported that it could inhibit increase of serum xanthine oxidase induced by liver tumor.OBJECTIVE: To investigate the protective effect of osthol on carbon tetrachloride (CCl4)-induced liver injury of mice.DESIGN: Completely randomized controlled study.SETTING: Department of Pharmacology, Gannan Medical College; Physical Education, Gannan Normal College.MATERIALS A total of 40 Kunming mice were of both genders and weighing (20±2) g. Osthol was provided by Chengdu Longquan High-Tech Natural Pharmaceutical Co. Ltd.METHODS: The experiment was performed at Department of Pharmacology, Gannan Medical College from March to July 2005. Forty mice were randomly divided into control, model, osthol (ip 50 g/kg) and osthol (ip 100 g/kg) groups with 10 in each. Separately once a day for 15 consecutive days, the control and model groups were equalized injected intraperitoneally with 10 mL/kg saline and osthol groups injected intraperitoneally with 50 and 100 g/kg osthol, respectively. On 15 day just after treatment,they, except the control, were challenged with CCl4 (ip 1 g/L peanut oil solution 10 mL/kg). Then all mice were free access to water but fast food.At specified time points 16 hours after the injection of CCl4, all mice were sacrificed and blood was collected in centrifuge tubes. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver malondialdehyde (MDA) were determined, and the pathological examination of liver was observed.MAIN OUTCOME MEASURES: Contents of serum ALT, AST, MDA and pathological examination.RESULTS: Forty mice were involved in the final analysis. ① At 16 hours after CCl4 induction, contents of ALT and AST were higher in model group than those in control group (P ＜ 0.001). The increase in the contents of ALT and AST was inhibited by osthol in a dose-dependent manner, especially in 100 mg/kg osthol group (P ＜ 0.05). Both 50 mg/kg and 100 mg/kg osthol could inhibit the increase of AST induced by CCl4 (P ＜ 0.01-0.001).② Content of MDA in model group was increased (P ＜ 0.05), and content of MDA in 100 mg/kg osthol group was similar to that in control group.100 mg/kg osthol could decrease content of MDA, 50 mg/kg osthol could increased the content; however, it still had the tendency of decrease. ③Effect of osthol on histopahtological changes, the livers of CCl4intoxicated mice showed massive fatty change, gross necrosis, broad infiltration of the lymphocytes, and Kupffer cells around the central vein, loss of cellular boundary. The histological pattern of the livers of the mice treated with 100 mg/kg and 50 mg/kg osthol showed a mild degree of fatty change,necrosis and lymphocyte infiltration. In contrast, the inhibitory potency of 100 mg/kg osthol on the histological changes significantly higher than those models.CONCLUSION: Osthol can protect against CCl4-induced hepatotoxicity in mice through decreasing activities ALT and AST and contents of MDA.