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2017 ; 53
(2
): 118-126
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Ameliorative Effects of Nilotinib on CCl4 Induced Liver Fibrosis Via Attenuation
of RAGE/HMGB1 Gene Expression and Oxidative Stress in Rat
#MMPMID28584790
Khanjarsim V
; Karimi J
; Khodadadi I
; Mohammadalipour A
; Goodarzi MT
; Solgi G
; Hashemnia M
Chonnam Med J
2017[May]; 53
(2
): 118-126
PMID28584790
show ga
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 CCL(4). Rats
were gavaged daily with Nilotinib (10 mg/kg). RAGE, HMGB1, TNF-? and TGF-? mRNA
expression were evaluated by quantitative RT-PCR. TNF-? 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-?,
TGF-?, 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.