4.6 Article

Does lithium attenuate the liver damage due to oxidative stress and liver glycogen depletion in experimental common bile duct obstruction?

期刊

TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 466, 期 -, 页码 -

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2023.116489

关键词

Lithium; Extrahepatic cholestasis; Glutamate; N-methyl-D-aspartate receptor; Hydrophobic bile acids; Liver glycogen

向作者/读者索取更多资源

This study suggests that activation of glutamatergic receptors may play a role in liver damage caused by bile acid accumulation. The use of lithium, a NMDAR-GluN2B subunit inhibitor, can protect the liver from oxidative stress and injury induced by bile acids. These findings provide important insights into the molecular mechanisms of cholestasis-induced liver damage and potential therapeutic strategies.
In extrahepatic cholestasis, the molecular mechanisms of liver damage due to bile acid accumulation remain elusive. In this study, the activation of glutamatergic receptors was hypothesized to be responsible for bile acid-induced oxidative stress and liver damage. Recent evidence showed that lithium, as an N-methyl-D-aspartate receptor (NMDAR) GluN2B subunit inhibitor, may act on the glutamate/NMDAR signaling axis. Guinea pigs were assigned to four groups, as sham laparotomy (SL), bile duct ligated (BDL), lithium-treated SL (SL + Li) and lithium-treated BDL (BDL + Li) groups. Cholestasis-induced liver injury was evaluated by aspartate amino-transferase (AST), alanine transaminase (ALT), interleukin-6 (IL-6), tissue malondialdehyde (MDA), copper-zinc superoxide dismutase and reduced glutathione levels. The liability of glutamate/NMDAR signaling axis was clarified by glutamate levels in both plasma and liver samples, with the production of nitric oxide (NO), as well as with the serum calcium concentrations. Blood glucose, glucagon, insulin levels and glucose consumption rates, in addition to tissue glycogen were measured to evaluate the liver glucose-glycogen metabolism. A high liver damage index (AST/ALT) was calculated in BDL animals in comparison to SL group. In the BDL animals, lithium reduced plasma NO and glutamate in addition to tissue glutamate concentrations, while serum calcium increased. The antioxidant capacities and liver glycogen contents significantly increased, whereas blood glucose levels unchanged and tissue MDA levels decreased 3-fold in lithium-treated cholestatic animals. It was concluded that lithium largely protects the cholestatic hepatocyte from bile acid-mediated damage by blocking the NMDAR-GluN2B subunit.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据