A comparison of the effects of infliximab, adalimumab and pentoxifylline on rats with non-alcoholoc steatohepititis

Aim: Due to the lack of effective medical treatment of non-alcoholic steatohepatitis (NASH), we aimed to evaluate new treatment options. Since tumor necrosis factor alpha (TNF-?) plays an important role in NASH, we aimed to investigate the treatment options affecting TNF-? during the development of NASH.Materials and Methods: Our study included a total of 35 male 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 infliximab, adalimumab or pentoxifylline. 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 anti-TNF. The TNF-? levels were detected to be as follows: 21.57±5.89 pg/ml in the group receiving a normal diet, 32.37±13.85 pg/ml in the group receiving the MCD diet, 22.86±16.15 pg/ml in the group treated with infliximab+MCD, 11.49±8.10 pg/ml in the group treated with MCD + adalimumab, and 29.67 ± 5.65 pg/ml in the group treated with MCD + pentoxifylline. There were no statistically significant differences observed between the three agents in terms of the histological NASH score. When comparing the total NASH scores between groups, the highest total score was 6.14±1.06 in the group receiving an MCD diet and no medication. The lowest total NASH score was 5.28±0.75 in the MCD+ adalimumab group. In addition, there were no significant differences between the groups treated with anti-TNF in terms of AST, ALT and ALP levels.Conclusion: Our study showed that the anti-TNF agents infliximab, adalimumab and pentoxifylline effectively suppress TNF-?, which plays an important role in NASH pathogenesis.Although these drugs do not prevent the development of NASH, it was shown that they could slightly reverse the NASH histopathology score and that they have positive effects on liver function tests.Key words: Non-alcoholic steatohepatitis, infliximab, adalimumab, pentoxifylline, rats.