Nilotinib alleviated acetaminophen-induced acute hepatic injury in mice through inhibiting HIF-1alpha/VEGF-signaling pathway

被引:8
作者
Menisy, Gehad M. [1 ]
Zakaria, Sherine [1 ]
Suddek, Ghada M. [2 ]
机构
[1] Kaferelsheikh Univ, Fac Pharm, Dept Pharmacol & Toxicol, Kaferelsheikh, Egypt
[2] Mansoura Univ, Fac Pharm, Dept Pharmacol & Toxicol, Mansoura 35516, Egypt
关键词
Acetaminophen; Liver injury; Hypoxia-inducible factor; Nilotinib; Vascular endothelial growth factor; ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; COVALENT BINDING; LIVER FIBROSIS; FREE-RADICALS; TOXICITY; TRANSCRIPTION; HIF-1-ALPHA; EXPRESSION; NECROSIS;
D O I
10.1016/j.intimp.2022.109268
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The current study inspects the impact of nilotinib (Nil) on liver damage caused by acetaminophen (APAP). Adult male mice were pre-treated with nilotinib (Nil,5 and 10 mg/kg) orally once daily for 7 days followed by a single intraperitoneal administration of acetaminophen (APAP, 200 mg/kg) on the 7th day. The results indicated that nilotinib significantly decreased APAP-induced elevation of biochemical markers (ALT, AST, ALP, LDH, gamma GT, and total bilirubin). Additionally, nilotinib significantly increased hepatic GSH and SOD content, while decreased MDA content. Nil significantly suppressed the expression of HIF-1 alpha and VEGF. Histopathological examination of hepatic tissue from Nil-treated mice revealed that Nil reduced acetaminophen-induced necrosis.
引用
收藏
页数:10
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