Protective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway

Context: Hepatic ischemia-reperfusion injury (HIRI) is a complex process observed during liver resection and transplantation. N-acetyl-l-tryptophan (l-NAT), an antagonist of neurokinin 1 receptor, has been used for the treatment of nausea and neurodegenerative diseases. Objective: This study investi...

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Autores principales:	Jianxin Wang, Shuna Yu, Jianguo Li, Huiting Li, Hongxin Jiang, Peilun Xiao, Yitong Pan, Jie Zheng, Li Yu, Jiying Jiang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	hepatic ischemia-reperfusion injury n-acetyl-l-tryptophan oxidative damaged Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/229e237879bc41e9af71bf72b8f470a7
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spelling	oai:doaj.org-article:229e237879bc41e9af71bf72b8f470a72021-11-17T14:21:56ZProtective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway1388-02091744-511610.1080/13880209.2019.1617750https://doaj.org/article/229e237879bc41e9af71bf72b8f470a72019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1617750https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: Hepatic ischemia-reperfusion injury (HIRI) is a complex process observed during liver resection and transplantation. N-acetyl-l-tryptophan (l-NAT), an antagonist of neurokinin 1 receptor, has been used for the treatment of nausea and neurodegenerative diseases. Objective: This study investigates the protective effect of l-NAT against HIRI and explores the potential underlying mechanisms. Materials and methods: Adult male Sprague-Dawley (SD) rats were randomly divided into three groups: sham, I/R and I/R + l-NAT. HIRI model was generated by clamping the hepatic artery, portal vein and common bile duct with a microvascular bulldog clamp for 45 min, and then removing the clamp and allowing reperfusion for 6 h. BRL cells were exposed to 200 µM H2O2 with or without 10 µM l-NAT for 6 h. Results: After l-NAT intervention, the structure of hepatic lobules was intact, and no swelling was noted in the cells. Furthermore, cell viability was found to be significantly enhanced when compared with the controls (p < 0.05). The mRNA and protein expression levels of serine-threonine kinase 2 (RIP2) and interleukin-1β (IL-1β) were significantly increased in the I/R and H2O2 groups when compared with the controls; however, these levels were significantly decreased after l-NAT intervention. Similarly, IL-1β activity and caspase-1 activity were significantly decreased in the H2O2 group when compared with the controls, after l-NAT intervention. Conclusions: Our findings indicated that l-NAT may exert a hepatoprotective role in HIRI through inhibiting RIP2/caspase-1/IL-1β signaling pathway, which can provide evidence for l-NAT to be a potential effective drug against HIRI during clinical practice.Jianxin WangShuna YuJianguo LiHuiting LiHongxin JiangPeilun XiaoYitong PanJie ZhengLi YuJiying JiangTaylor & Francis Grouparticlehepatic ischemia-reperfusion injury n-acetyl-l-tryptophan oxidative damagedTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 385-391 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatic ischemia-reperfusion injury n-acetyl-l-tryptophan oxidative damaged Therapeutics. Pharmacology RM1-950
spellingShingle	hepatic ischemia-reperfusion injury n-acetyl-l-tryptophan oxidative damaged Therapeutics. Pharmacology RM1-950 Jianxin Wang Shuna Yu Jianguo Li Huiting Li Hongxin Jiang Peilun Xiao Yitong Pan Jie Zheng Li Yu Jiying Jiang Protective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway
description	Context: Hepatic ischemia-reperfusion injury (HIRI) is a complex process observed during liver resection and transplantation. N-acetyl-l-tryptophan (l-NAT), an antagonist of neurokinin 1 receptor, has been used for the treatment of nausea and neurodegenerative diseases. Objective: This study investigates the protective effect of l-NAT against HIRI and explores the potential underlying mechanisms. Materials and methods: Adult male Sprague-Dawley (SD) rats were randomly divided into three groups: sham, I/R and I/R + l-NAT. HIRI model was generated by clamping the hepatic artery, portal vein and common bile duct with a microvascular bulldog clamp for 45 min, and then removing the clamp and allowing reperfusion for 6 h. BRL cells were exposed to 200 µM H2O2 with or without 10 µM l-NAT for 6 h. Results: After l-NAT intervention, the structure of hepatic lobules was intact, and no swelling was noted in the cells. Furthermore, cell viability was found to be significantly enhanced when compared with the controls (p < 0.05). The mRNA and protein expression levels of serine-threonine kinase 2 (RIP2) and interleukin-1β (IL-1β) were significantly increased in the I/R and H2O2 groups when compared with the controls; however, these levels were significantly decreased after l-NAT intervention. Similarly, IL-1β activity and caspase-1 activity were significantly decreased in the H2O2 group when compared with the controls, after l-NAT intervention. Conclusions: Our findings indicated that l-NAT may exert a hepatoprotective role in HIRI through inhibiting RIP2/caspase-1/IL-1β signaling pathway, which can provide evidence for l-NAT to be a potential effective drug against HIRI during clinical practice.
format	article
author	Jianxin Wang Shuna Yu Jianguo Li Huiting Li Hongxin Jiang Peilun Xiao Yitong Pan Jie Zheng Li Yu Jiying Jiang
author_facet	Jianxin Wang Shuna Yu Jianguo Li Huiting Li Hongxin Jiang Peilun Xiao Yitong Pan Jie Zheng Li Yu Jiying Jiang
author_sort	Jianxin Wang
title	Protective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway
title_short	Protective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway
title_full	Protective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway
title_fullStr	Protective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway
title_full_unstemmed	Protective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway
title_sort	protective role of n-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the rip2/caspase-1/il-1β signaling pathway
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/229e237879bc41e9af71bf72b8f470a7
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Protective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway

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