A comparison of the effects of n-acetylcysteine and adalimumab on rats with non-alcoholic steatohepititis

Aim: Due to the lack of effective medical treatment of non-alcoholic steatohepatitis (NASH), we aimed to evaluate an anti- TNF-? agent adalimumab as a new treatment option and compare with N-acetylcysteine that suppress oxidative stress. Since tumor necrosis factor alpha (TNF-?) and oxidative stress play an important role in NASH, we aimed to investigate the treatment option affecting TNF-? during the development of NASH and compare it with N-acetylcysteine attenuates oxidative stress and liver pathology in rats with NASH. Materials and Methods: Our study included a total of 35 female Wistar albino rats that were divided into 5 groups of 7 each, and evaluated over a 6 week period. One group received a normal diet, while the other four groups received a methionine and choline deficient (MCD) diet. One of the groups receiving an MCD diet did not take any medicine, while the other three were administered N-acetylcysteine, adalimumab or N-acetylcysteine-adalimumab combination therapy. Rats were sacrificed after six weeks. The aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, total protein, albumin, TNF-?, transforming growth factor-beta (TGF-ß), interleukin 6 (IL-6), interleukin 8 (IL-8) levels were determined from the rats? serum samples. Liver tissue samples were assessed for the presence of fatty liver, ballooning degeneration, lobular inflammation, and fibrosis. Results: NASH was successfully created in the MCD diet group. Levels of TNF-? were effectively suppressed in the three groups that received therapy. The TNF-? levels were detected to be as follows: 0,99 (0,13-7,42) pg/ml in the group receiving a normal diet, 9,90 (2,23-11,64) pg/ml in the group receiving the MCD diet, 3,75 (1,97-13,14) pg/ml in the group treated with MCD+NAC, 1,90 (1,09-2,58) pg/ml in the group treated with MCD + adalimumab and 1,33 (1,12-4,24) pg/ml in the group treated with MCD+NAC+adalimumab. Decrease in total NASH score was statistically significant in MCD+NAC and MCD+NAC+adalimumab groups (p=0,037-0,007) compared with MCD+adalimumab group but it was not statistically significant between MCD+NAC and MCD+NAC+adalimumab groups (p=0,381). When comparing the total NASH scores between groups, the highest total score was 6.15±1.07 in the group receiving MCD diet and no medication. The lowest total NASH score was 5.00±1.16 in the MCD+NAC+adalimumab group. In addition, in AST, ALT (except MCD+adalimamab group) and ALP (except MCD+NAC group) levels statistically unsignificant improvement was observed. Conclusion: Our study showed that TNF? and oxidative stress play an important role in NASH pathogenesis. Antioxidant agent N-acetylcysteine was found to be superior to the anti-TNF agent adalimumab in improvement of total NASH score. Although these drugs do not prevent the development of NASH, it was shown that they could mildly reverse the NASH histopathology score and may improve liver function tests. Key words: Non-alcoholic steatohepatitis, N-acetylcysteine, adalimumab, rats.