The serum and tissue levels of TNF alpha and the apoptotic index

The serum and tissue levels of TNF alpha and the apoptotic index in the nilotinib group were found to be similar to those in the figure 2 TNBS group. Previously, it has been shown that TNF alpha levels on day 7 are significantly higher in acute models of colitis established through a single dose application of TNBS, compared to the model of chronic colitis using weekly TNBS administrations[29,30]. That the serum and tissue TNF alpha levels were similar in the nilotinib and TNBS groups in our study might be explained by the length of the experiment (14 d), during which a TNF alpha peak could not be obtained. Additionally, the apoptosis indices were similar between both groups in our study. D��Argenio et al[31] demonstrated the apoptotic cells and expressions of apoptotic proteins in TNBS-induced colitis over 4 wk.

According to the results of this study, the apoptotic cell count was detected to be significantly decreased after first week by the TUNEL method[31]. The similar apoptotic scores detected in our study might be because the apoptotic cell peak could not be obtained after 14 d. Furthermore, the similar results of the TNF alpha levels and apoptosis scores in our study might also suggest that nilotinib has no significant effect on TNF alpha levels and apoptosis. In conclusion, nilotinib has a significant effect on weight loss, as well as on the macroscopic and microscopic pathological scores in rats with TNBS-induced colitis, leading to significant mucosal healing. Although nilotinib caused a decrease in PDGFR alpha and PDGFR beta levels, it did not have a significant effect on apoptotic scores or TNF alpha levels.

COMMENTS Background Genetic and environmental factors, infectious agents, the structure of enteric flora, and immune system dysfunction are key elements in the pathogenesis of inflammatory bowel disease (IBD); thus, these are the targets for many drugs developed to treat IBD. Unresponsiveness to medical treatments in refractory IBD still poses a therapeutic challenge. Tyrosine kinases (TKs) are enzymes that play a role in normal cell function, metabolism, growth, differentiation, and apoptosis. To establish an alternative treatment option, they selected nilotinib based on the fact that TK inhibitors affect several key components in the pathogenesis of IBD, including tumor necrosis factor (TNF) alpha, platelet-derived growth factor receptor (PDGFR), and apoptosis.

Research frontiers Nilotinib is a TK inhibitor that is typically used as an anticancer drug. Recently, it has been considered for use in noncancerous proliferative diseases and for inflammatory conditions. Authors concluded that nilotinib has a significant effect
Hepatitis C virus (HCV) causes acute and chronic Carfilzomib hepatitis. The mechanisms that determine progression to chronic infection and outcome of HCV infection are not well understood.

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