Nilotinib as a tyrosine kinase inhibitor has been recently used to improve the liver fibrosis process, but the exact mechanisms still require further clarification. In this study, we investigated the anti-fibrotic effects of Nilotinib via RAGE/HMGB1axis and antioxidant mechanisms. This experimental study was performed in the Hamadan University of Medical Sciences, Iran, from May 2015 to December 2016. Liver fibrosis was induced in Wistar male rats by CCL₄. Rats were gavaged daily with Nilotinib (10 mg/kg). RAGE, HMGB1, TNF-α and TGF-β mRNA expression were evaluated by quantitative RT-PCR. TNF-α protein levels were measured using the immunoassay method. Thiol groups, carbonyl groups, nitric oxide levels and glutathione peroxidase activity were measured by spectrophotometric methods.The results showed that Nilotinib decreased TNF-α, TGF-β, RAGE and HMGB1 mRNA expression (p<0.001) in the liver tissues of the fibrosis group. Nilotinib also decreased carbonyl groups and nitric oxide levels and increased thiol groups and glutathione peroxidase activity in the fibrosis groups. The histopathological changes were found to be attenuated by Nilotinib. In conclusion, Nilotinib can improve liver fibrosis and open new mechanisms of the anti-fibrotic properties of Nilotinib.
Animals ; Fibrosis ; Gene Expression ; Glutathione Peroxidase ; HMGB1 Protein ; Humans ; Immunoassay ; Iran ; Liver Cirrhosis ; Liver ; Male ; Methods ; Nitric Oxide ; Oxidative Stress ; Protein-Tyrosine Kinases ; Rage ; Rats ; RNA, Messenger

Objective To evaluated the relationship between the genetic variations at IL-8 +2767 position with VL pathogenesis among Iranian patients. Methods Three groups including patients with VL clinical presentation and leishmania seropositive (n = 124), patients seropositive but without clinical presentation (n = 82) and healthy controls (n = 63) were selected to conduct this cross-sectional study. Polymorphism at +2767 position of IL-8 was investigated using PCR-RFLP techniques. Anti-leishmania antibody titration was evaluated by the immunoflorescence technique. Results We observed higher significant frequencies +2767 A/A and A/T genotypes in Group 1 compared to Group 2 and healthy controls (P = 0.001). Also, patients in Group 1 carrying A/A genotype showed higher titer of anti-leishmania antibody than patients with A/T and T/T genotypes (P = 0.05). The validity of the data was analyzed using Hardy–Weinberg equilibrium and one way analysis of variance (ANOVA), as well as χ