Therapeutic effect of low dose acetylcysteine on rats with chronic hepatic injury

Abstract

Objective To investigate the effect of low dose acetylcysteine (NAC) on carbon tetrachloride (CCl4) induced chronic hepatic injury in rats. Methods A total of 93 SD rats were ranged into control group (n=15) and model group (n=78) . Rats in model and control group were given 25% CCl4 olive oil solution and olive oil 1 mL/kg respectively by subcutaneous injection, 3 times a week continuously for 4 weeks. At the end of the fourth week, 3 rats were randomly selected from the model group for pathological section, and observed the severity of liver damage. At the same time, 75 rats with chronic hepatic injury were ranged into 5 groups with 15 rats in each groups with NAC 45, 90, 180 mg/kg, positive model group and model group. Rats in positive model group were given 54 mg/kg glutathione (GSH) , and rats in control group and model group were given the same volume sterilized normal sodium, once a day by intraperitoneal injection for 4 weeks. The rats were narcotized and took blood from aorta abdominalis, hepatic function indices including ALT, AST, albumin (ALB) , ALP and TBil in serum were detected 24 hours after the last administration, Livers were taken and weighted, and malonaldehyde (MDA) , hydroxyproline (Hyp) , GSH content and superoxide dismutase (SOD) activity in hepatic tissue were detected. The residual liver was fixed with 10% formalin, and the histopathological changes were observed. Results The differences of ALT, AST, ALP, ALB and TBil in each group were statistically significant (F=16.878, 9.996, 6.099, 5.002, 11.157, P<0.01) . Compared with rats in control group, levels of ALT, AST, ALP and TBil in serum in model group, which were (112.00±19.05) U/L, (150.67±18.15) U/L, (272.75±34.26) U/L and (1.98±0.10) U/L respectively, were significantly higher (t=26.912, P<0.01; t=15.571, P<0.01; t=8.238, P<0.05; t=14.367, P<0.01) . The differences of SOD, MDA, GSH and Hyp among each group had statistical significance (F=3.251, P<0.05; F=3.232, P<0.05; F=5.210, P<0.01; F=41.131, P<0.01) . The liver MDA and Hyp in model group were (0.99±0.22) nmol/mgprot and (504.05±84.51) μg/g, which were higher than the control group (t=8.229 and 69.853, P<0.01) . GSH, Hyp and SOD in the small dose NAC group and middle dose group were higher than model group with significant differences (P all<0.05) . GSH in high dose group was (1.53±0.76) μmol/gprot which was higher than model group, while Hyp inmodel group in high dose group was (131.53±44.85) μg/g which was lower than model group (t=6.023, P<0.05; t=58.532, P<0.01) . The HE staining results showed that all NAC groups could relieve the degree of chronic hepatic injury obviously. Conclusions Low dose NAC can prevent CCl4 induced chronic hepatic injury in rats. Key words: Acetylcysteine; Carbon tetrachloride; Chronic hepatic injury