格拉司琼
医学
上睑下垂
败血症
炎症
药理学
氧化应激
肝损伤
麻醉
内科学
化疗
止吐药
炎症体
作者
Amira M. Abo‐Youssef,Mostafa Kamal Mohammad,Ali A. Abo‐Saif,Basim Anwar Shehata Messiha
标识
DOI:10.1016/j.jphs.2021.08.005
摘要
Sepsis induced liver injury is recognized as a serious complication in intensive care units, it is deeply associated with oxidative stress, inflammation and subsequent pyroptosis. Hepatic pyroptosis known to aggravate sepsis-induced liver injury. Previous studies proved that granisetron has anti-inflammatory and antioxidant properties. Accordingly, this study aimed to evaluate the efficacy of granisetron on sepsis-induced liver damage using a cecal ligation and puncture (CLP) model in rats.Male albino rats were randomly divided into four groups: a sham control group, a granisetron control group, a CLP-induced sepsis group and a granisetron-treated CLP group. Markers of oxidative stress, inflammation, pyroptosis-related proteins and liver function were measured in addition to the histopathological study.Granisetron pretreatment significantly decreased mortality and improved liver function, as indicated by decreased ALT, AST, and total bilirubin and increased albumin content. Moreover, granisetron increased GPx activity and downregulated hepatic MDA. Furthermore, granisetron administration significantly reduced TNF-α, IL-6, HMGB1 and NF-κB. It also decreased the expression of receptor for advanced glycation end and TLR4 in the liver tissue. Interestingly, granisetron inhibited pyroptosis as it reduced NLRP3, IL-1β and caspase-1. Granisetron was shown to increase Nrf2 and HO-1. In addition, granisetron treatment repaired, to some extent, the abnormal architecture of hepatic tissue.Our results suggested that granisetron is a potential therapeutic agent for sepsis-associated liver injury, possibly acting by inhibiting oxidative stress, inflammation and subsequent pyroptosis.
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