文章基本信息

标题：Metformin inhibits expression of the proinflammatory biomarker inducible nitric oxide synthase in hepatocytes
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作者：Richi Nakatake ; Hiroya Iida ; Morihiko Ishizaki 等
期刊名称：Functional Foods in Health and Disease
电子版ISSN：2160-3855
出版年度：2018
卷号：8
期号：3
页码：175-192
语种：English
出版社：Food Science Publisher
其他摘要：Background: Metformin is used to treat patients with type II diabetes. However, there are few scientific reports on its anti-inflammatory effects. In the inflamed liver, proinflammatory cytokines stimulate liver cells, followed by inducible nitric oxide synthase (iNOS) expression. Excessive NO levels produced by iNOS have been implicated as a factor in liver injury. As a result, it is essential to inhibit iNOS induction to prevent liver injury. Objective : This study aimed to investigate liver protective effects of metformin by examining interleukin (IL)-1β-stimulated hepatocytes. Methods: Primary cultured rat hepatocytes were treated with interleukin (IL)-1β in the presence or absence of metformin. iNOS induction and its signaling pathway were analyzed. Results: Metformin decreased iNOS protein and mRNA expression, resulting in the inhibition of hepatic NO production. Metformin also reduced tumor necrosis factor (TNF)-α and IL-6 mRNA expression. Metformin inhibited an essential signaling pathway for iNOS induction, type I IL-1 receptor upregulation. Transfection experiments revealed that metformin reduced iNOS mRNA levels through both promoter transactivation and mRNA stabilization. Delayed metformin administration after IL-1β addition also inhibited iNOS induction. Conclusions: Metformin affects the induction of inflammatory mediators including iNOS and TNF-α, demonstrating its therapeutic potential for organ injuries, including the liver. {end} metformin, inducible nitric oxide synthase, liver injury, primary cultured hepatocytes, type I interleukin-1 receptor, tumor necrosis factor-α