Vitamin B6 Alleviates Lipopolysaccharide-induced Myocardial Injury by Ferroptosis and Apoptosis Regulation

Meirong Shan; Xujie Yu; Yajie Li; Changning Fu; Cheng Zhang

doi:10.3389/fphar.2021.766820

Vitamin B6 Alleviates Lipopolysaccharide-induced Myocardial Injury by Ferroptosis and Apoptosis Regulation

Front Pharmacol. 2021 Dec 24:12:766820. doi: 10.3389/fphar.2021.766820. eCollection 2021.

Authors

Meirong Shan^{1

2}, Xujie Yu¹, Yajie Li³, Changning Fu⁴, Cheng Zhang¹

Affiliations

¹ The Key Laboratory of Cardiovascular Remodeling and Function Research, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China.
² Department of Geriatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
³ Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Abstract

Vitamin B6 (VitB6) is a water-soluble vitamin and includes pyridoxine, pyridoxal, pyridoxamine, and their phosphorylated forms. In the current study, we demonstrated that VitB6 could improve lipopolysaccharide (LPS)-induced myocardial injury. We demonstrated that VitB6 can suppress LPS-induced oxidative stress and lipid peroxidation that lead to ferroptosis and apoptosis in vivo and in vitro. Moreover, we found that VitB6 can regulate the expression of iron regulatory proteins, maintaining intracellular iron homeostasis. To confirm that VitB6 could inhibit LPS-induced ferroptosis and apoptosis, we pretreated mice with ferrostatin-1 (Fer-1) and emricasan that efficiently mimicked VitB6 pharmacological effects. This improved the survival rate of mice challenged with a high LPS dose. In addition, VitB6 regulated the expression of LPS-induced apoptosis-related proteins and iron regulatory proteins. It mediated the expression of Nrf2, transcription factor NF-E2-related factor 2, which promoted the expression of antioxidant enzymes and restrained LPS-induced ferroptosis and apoptosis. Overall, our results indicated that VitB6 can be used on novel therapies to relieve LPS-induced myocardial injury.

Keywords: Nrf2; apoptosis; ferroptosis; lipopolysaccharide; myocardial injury; vitamin B6.