Mitochondrial antioxidant MitoQ alleviates nitrogen mustard-induced acute liver injury in mice
Journal Title: Journal of Air Force Medical University - Year 2023, Vol 44, Issue 3
Abstract
Objective To investigate the protective effect and related mechanism of mitochondrial antioxidant mitoquinone mesylate (MitoQ) on nitrogen mustard ( HN2)-induced acute liver injury ( ALI) in mice. Methods Forty male C57BL / 6 mice were randomly divided into four groups: control group, MitoQ control group, HN2 exposure group, and MitoQ + HN2 group ( MitoQ treatment group ). The following indicators were detected: body mass, serum alanine aminotransferase ( ALT) and aspartate aminotransferase ( AST) activities; Bcl-2 and Bax protein expression, caspase-3 activity, and proportion of apoptotic cells in liver tissues; pathological structural changes detected by HE staining in liver tissues; serum blood glucose level, triglyceride (TG) level in serum and liver tissues; neutral fat content in liver detected by oil red O staining; malondialdehyde ( MDA) content in liver tissues, reduced glutathione and reactive oxygen species(ROS) levels; and concentrations of serum inflammatory factors such as TNF-α and IL-6. Results Intraperitoneal administration of 2 mg / kg HN2 could successfully induce ALI in mice, accompanied by glucose and lipid metabolism disorders. Compared with mice in HN2 exposure group, the serum ALT and AST activities were decreased (P < 0. 05), the degree of liver pathological damage was significantly alleviated, Bax / Bcl-2 ratio, caspase-3 activity and proportion of apoptotic cells were decreased (P < 0. 05), the content of TG in liver tissues was significantly increased (P < 0. 05), while the levels of MDA and ROS in liver tissues were significantly reduced ( P < 0. 05 ) in MitoQ treatment group. In addition, the concentrations of serum TNF-α and IL-6 in mice with MitoQ intervention were significantly lower than those in HN2 exposure group. Conclusion MitoQ plays an antagonistic role against HN2-induced ALI in mice through anti-apoptosis, antioxidation and anti-inflammatory effects, and may be a potential drug candidate for HN2 poisoning. This study provides new ideas for the clinical treatment of blister agent poisoning.
Authors and Affiliations
LIU Jiangzheng, SONG Dexin, MA Chengfei, LIU Sijia, ZHAO Yushun, LIU Jianhao, XU Anqi, AI Duo,LONG Zi, KONG Deqin, HAI Chunxu
Keywords
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