The augment effects of magnesium hydride on the lipid lowering effect of atorvastatin: an in vivo and in vitro investigation

Chen, Wanqiu1,#; Zhang, Yinyin2,#; Miao, Gen2,#; Ying, Yajing2,#; Ren, Zifu2; Sun, Xuejun2,3; Cai, Jianming1,2,*; Shen, Hui2,*; Lu, Hongtao2,*

¹School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang Province, China²Department of Naval Medicine, Naval Medical University, Shanghai, China³Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai, China

Abstract

There is strong evidence connecting increased serum lipid levels to cardiovascular disorders, including atherosclerosis. Statins is prescribed as the primary medication to decrease lipid levels. Recent research has demonstrated that hydrogen possesses anti-inflammatory and antioxidant properties by modulating the expression of peroxisome proliferator-activated receptor gamma coactivator-1α, ultimately leading to the preservation of lipid homeostasis. Magnesium hydride (MgH₂) is a prolonged stable hydrogen storage medium, which can be utilized to investigate its synergistic lipid-lowering effect with statins and its detailed molecular mechanism, both in vivo and in vitro. To ascertain the safety and efficacy of MgH₂, we executed a comprehensive research of its influence on both physiological and pathological metrics. We noted a substantial diminution in lipid levels when MgH₂ was integrated with atorvastatin, as attested by oil red staining. Furthermore, we scrutinized the regulatory effect of MgH₂ on cytochrome P450 3A, which is a metabolic enzyme of statins, and discovered that it could be reduced by the MgH₂. Concluding from our results, we propose that MgH₂ inhibits the expression of cytochrome P450 3A in the liver and exerts an auxiliary lipid-lowering effect by increasing the blood concentration of statins. By augmenting our comprehension of MgH₂’s role in ameliorating lipid metabolism, we aspire to develop more promising therapies in the future.

氢化镁与阿托伐他汀协同降脂作用的体内外研究

摘要：有强有力的证据表明，高血脂与动脉粥样硬化等心血管疾病有关。他汀类药物是降低血脂水平的主要药物。最近有研究表明，氢可通过调节PGC-1α的表达，发挥抗炎和抗氧化作用，进而维持脂质稳态。氢化镁（MgH2）是一种长期稳定的储氢介质，可用于探索与他汀类药物的协同降脂作用及分子机制。实验发现，当MgH2与阿托伐他汀结合时，脂质水平显著降低。此外实验还探索了MgH2对他汀类药物的代谢酶CYP3A的调节作用，可见CYP3A可被MgH2还原。综上得出，MgH2可抑制肝脏中CYP3A的表达，并通过增加他汀类药物的血液浓度发挥辅助降脂作用。这一结果扩展了对MgH2改善脂质代谢作用的理解，有望为未来血脂异常治疗开发潜在疗法。