China Animal Husbandry and Veterinary Medicine ›› 2022, Vol. 49 ›› Issue (5): 1888-1894.doi: 10.16431/j.cnki.1671-7236.2022.05.029

• Basic Veterinary Medicine • Previous Articles     Next Articles

Mitigating Effect and Mechanism of JNK Inhibitor on Drug-induced Injury of Piglet Hepatocytes

WANG Ben, YUAN Shuai, ZHENG Yi, ZHANG Hongling   

  1. College of Animal Science, Jilin Agricultural Science and Technology College, Jilin 132101, China
  • Received:2021-11-17 Online:2022-05-05 Published:2022-04-29

Abstract: 【Objective】 The aim of this study was to investigate the alleviating effect and mechanism of c-Jun N-terminal kinase (JNK) inhibitor SP600125 on the pharmacological damage of primary hepatocytes in piglets.【Method】 Piglet primary hepatocytes were obtained by two-step perfusion method,and the hepatocytes were divided into control group (C),JNK inhibitor group (SP),model group (M) and treatment group (T),with 6 replicates in each group.The cells in control group were not added with drugs,SP group cells were treated with 2 μmol/L SP600125,M group cells were treated with 80 μg/mL lipopolysaccharide (LPS) +20 μg/mL enrofloxacin (ENR),T group cells were treated with 80 μg/mL LPS+20 μg/ mL ENR+2 μmol/L SP600125.After treatment for 12 h,supernatants were collected to determine alanine transaminase (ALT) and glutamic oxalacetic transaminase (AST) activities,and cells were collected to determine the activities of glutathione peroxidase (GSH-Px),superoxide dismutase (SOD), and the content of malondialdehyde (MDA) and the relative expression of hepatocyte nuclear factor 1 (HNF-1) and glutathione S-transferase alpha 1 (GSTA1) mRNA.【Result】 Compared with control group,the activities of ALT and AST in hepatocyte culture medium were significantly increased in M group (P<0.05),the activities of GSH-Px,SOD and the relative expression of HNF-1,GSTA1 mRNA in hepatocytes were extremely significantly decreased in M group (P<0.01),and MDA content in hepatocytes was extremely significantly increased (P<0.01).Compared with M group,the activities of ALT and AST in hepatocyte culture medium were significantly decreased in T group (P<0.05),the activities of GSH-Px,SOD and the relative expression of HNF-1,GSTA1 mRNA in hepatocytes were significantly increased in T group (P<0.05),and MDA content was significantly decreased (P<0.05).【Conclusion】 JNK inhibitor SP600125 could alleviate the drug-induced injury of piglet primary hepatocytes caused by LPS/ENR by regulating the antioxidant capacity and the expression of HNF-1 and GSTA1 of cells.

Key words: primary hepatocytes; drug-induced injury; JNK inhibitor; anti-oxidation

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