Omaveloxolone attenuates the sepsis-induced cardiomyopathy via activating the nuclear factor erythroid 2-related factor 2

作者：Jian, Wenting; Ma, Huigai; Wang, Dingming; Yang, Peng; Jiang, Mengbi; Zhong, Yu; Long, Xiang; Jiang, Jingjing; Gong, Yuan^*

来源：International Immunopharmacology, 2022, 111: 109067.

DOI：10.1016/j.intimp.2022.109067

• Omaveloxolone
• Sepsis -induced cardiomyopathy
• Nuclear factor erythroid 2-related factor 2
• (Nrf2)
• Oxidative stress
• Inflammation

Sepsis-induced cardiomyopathy (SIC) is a common complication of sepsis and is the main reason for the high mortality in sepsis patients. More recent studies have indicated that activating nuclear factor erythroid 2-related factor 2 (Nrf2) signaling plays a protective role in SIC. As a potent activator of Nrf2, Omaveloxolone plays a pivotal role in defending against oxidative stress and the inflammatory response. Thus, we examined the efficacy of omaveloxolone in SIC. In the present study, the mice were injected intraperitoneally with a single dose of LPS (10 mg/kg) for 12 h to induce SIC. The data in our study indicated that omaveloxolone administration significantly improved cardiac injury and dysfunction in LPS-induced SIC. In addition, omaveloxolone administration reduced SIC-related cardiac oxidative stress, the inflammatory response and cardiomyocyte apoptosis in mice. In addition, omaveloxolone administration also improved LPS-induced cardiomyocyte injury in an in vitro model using H9C2 cells. Moreover, knockdown of Nrf2 by si-Nrf2 abolished the omaveloxolone-mediated cardioprotective effects. In conclusion, omaveloxolone has potent cardioprotective potential in treating sepsis and SIC via activation of the Nrf2 signaling pathway.

• 单位
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