Downregulation of the NLRP3/Caspse-1 Pathway Ameliorates Ketamine-Induced Liver Injury and Inflammation in Developing Rats

Ketamine is an anesthetic drug that is widely used in human and veterinary medicine. In the developmental stage, long-term exposure to ketamine may cause serious side effects. MCC950 and VX765 play protective roles in many disease models by regulating the NLRP3/Caspase-1 pathway. This study aims to...

Full description

Bibliographic Details
Main Authors: Xinzhang Chen, Zhiheng Zhang, Meilun Shen, Xiangying Ma, Di Qiu, Siyao Li, Li Gao
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/9/2931
_version_ 1797503634551865344
author Xinzhang Chen
Zhiheng Zhang
Meilun Shen
Xiangying Ma
Di Qiu
Siyao Li
Li Gao
author_facet Xinzhang Chen
Zhiheng Zhang
Meilun Shen
Xiangying Ma
Di Qiu
Siyao Li
Li Gao
author_sort Xinzhang Chen
collection DOAJ
description Ketamine is an anesthetic drug that is widely used in human and veterinary medicine. In the developmental stage, long-term exposure to ketamine may cause serious side effects. MCC950 and VX765 play protective roles in many disease models by regulating the NLRP3/Caspase-1 pathway. This study aims to explore the potential protective effect of MCC950 and VX765 on ketamine-induced liver injury in neonatal rats and clarify its underlying mechanism. After administration of MCC950 and VX765 in a ketamine-induced liver injury rat model, liver function and inflammatory factors were determined, and immunohistochemistry and western blotting were performed. We found that ketamine caused liver injury in 7-day-old SD rats, decreased liver function indexes, and increased inflammation. MCC950 and VX765 effectively alleviated liver damage and inflammation, and downregulated the expression of proteins such as NLRP3, Caspase-1, and GSDMD-N. In summary, these results indicated that MCC950 and VX765 could have potential protective effects on ketamine-induced liver injury through inhibiting the NLRP3/Caspase-1 pathway.
first_indexed 2024-03-10T03:53:30Z
format Article
id doaj.art-425cb03104234d42985e28f02284799a
institution Directory Open Access Journal
issn 1420-3049
language English
last_indexed 2024-03-10T03:53:30Z
publishDate 2022-05-01
publisher MDPI AG
record_format Article
series Molecules
spelling doaj.art-425cb03104234d42985e28f02284799a2023-11-23T08:51:46ZengMDPI AGMolecules1420-30492022-05-01279293110.3390/molecules27092931Downregulation of the NLRP3/Caspse-1 Pathway Ameliorates Ketamine-Induced Liver Injury and Inflammation in Developing RatsXinzhang Chen0Zhiheng Zhang1Meilun Shen2Xiangying Ma3Di Qiu4Siyao Li5Li Gao6College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaKetamine is an anesthetic drug that is widely used in human and veterinary medicine. In the developmental stage, long-term exposure to ketamine may cause serious side effects. MCC950 and VX765 play protective roles in many disease models by regulating the NLRP3/Caspase-1 pathway. This study aims to explore the potential protective effect of MCC950 and VX765 on ketamine-induced liver injury in neonatal rats and clarify its underlying mechanism. After administration of MCC950 and VX765 in a ketamine-induced liver injury rat model, liver function and inflammatory factors were determined, and immunohistochemistry and western blotting were performed. We found that ketamine caused liver injury in 7-day-old SD rats, decreased liver function indexes, and increased inflammation. MCC950 and VX765 effectively alleviated liver damage and inflammation, and downregulated the expression of proteins such as NLRP3, Caspase-1, and GSDMD-N. In summary, these results indicated that MCC950 and VX765 could have potential protective effects on ketamine-induced liver injury through inhibiting the NLRP3/Caspase-1 pathway.https://www.mdpi.com/1420-3049/27/9/2931ketaminedeveloping ratsliversNLRP3/Caspase-1
spellingShingle Xinzhang Chen
Zhiheng Zhang
Meilun Shen
Xiangying Ma
Di Qiu
Siyao Li
Li Gao
Downregulation of the NLRP3/Caspse-1 Pathway Ameliorates Ketamine-Induced Liver Injury and Inflammation in Developing Rats
Molecules
ketamine
developing rats
livers
NLRP3/Caspase-1
title Downregulation of the NLRP3/Caspse-1 Pathway Ameliorates Ketamine-Induced Liver Injury and Inflammation in Developing Rats
title_full Downregulation of the NLRP3/Caspse-1 Pathway Ameliorates Ketamine-Induced Liver Injury and Inflammation in Developing Rats
title_fullStr Downregulation of the NLRP3/Caspse-1 Pathway Ameliorates Ketamine-Induced Liver Injury and Inflammation in Developing Rats
title_full_unstemmed Downregulation of the NLRP3/Caspse-1 Pathway Ameliorates Ketamine-Induced Liver Injury and Inflammation in Developing Rats
title_short Downregulation of the NLRP3/Caspse-1 Pathway Ameliorates Ketamine-Induced Liver Injury and Inflammation in Developing Rats
title_sort downregulation of the nlrp3 caspse 1 pathway ameliorates ketamine induced liver injury and inflammation in developing rats
topic ketamine
developing rats
livers
NLRP3/Caspase-1
url https://www.mdpi.com/1420-3049/27/9/2931
work_keys_str_mv AT xinzhangchen downregulationofthenlrp3caspse1pathwayamelioratesketamineinducedliverinjuryandinflammationindevelopingrats
AT zhihengzhang downregulationofthenlrp3caspse1pathwayamelioratesketamineinducedliverinjuryandinflammationindevelopingrats
AT meilunshen downregulationofthenlrp3caspse1pathwayamelioratesketamineinducedliverinjuryandinflammationindevelopingrats
AT xiangyingma downregulationofthenlrp3caspse1pathwayamelioratesketamineinducedliverinjuryandinflammationindevelopingrats
AT diqiu downregulationofthenlrp3caspse1pathwayamelioratesketamineinducedliverinjuryandinflammationindevelopingrats
AT siyaoli downregulationofthenlrp3caspse1pathwayamelioratesketamineinducedliverinjuryandinflammationindevelopingrats
AT ligao downregulationofthenlrp3caspse1pathwayamelioratesketamineinducedliverinjuryandinflammationindevelopingrats