Reductive stress is defined as a condition of sustained increase in cellular glutathione/glutathione disulfide and NADH/NAD⁺ ratios. Reductive stress is emerging as an important pathophysiological event in several diseased states, being as detrimental as is oxidative stress. Occurrence of reductive stress has been documented in several cardiomyopathies and is an important pathophysiological factor particularly in coronary artery disease and myocardial infarction. Excess activation of the transcription factor, Nrf2—the master regulator of the antioxidant response—, consequent in most cases to defective autophagy, can lead to reductive stress. In addition, hyperglycemia-induced activation of the polyol pathway can lead to increased NADH/NAD⁺ ratio, which might translate into increased levels of hydrogen sulfide—via enhanced activity of cystathionine β-synthase—that would fuel reductive stress through inhibition of mitochondrial complex I. Reductive stress may be either a potential weapon against cancer priming tumor cells to apoptosis or a cancer’s ally promoting tumor cell proliferation and making tumor cells resistant to reactive oxygen species-inducing drugs. In non-cancer pathological states reductive stress is definitely harmful paradoxically leading to reactive oxygen species overproduction via excess NADPH oxidase 4 activity. In face of the documented occurrence of reductive stress in several heart diseases, there is much less information about the occurrence and effects of reductive stress in skeletal muscle tissue. In the present review we describe relevant results emerged from studies of reductive stress in the heart and review skeletal muscle conditions in which reductive stress has been experimentally documented and those in which reductive stress might have an as yet unrecognized pathophysiological role. Establishing whether reductive stress has a (patho)physiological role in skeletal muscle will hopefully contribute to answer the question whether antioxidant supplementation to the general population, athletes, and a large cohort of patients (e.g. heart, sarcopenic, dystrophic, myopathic, cancer, and bronco-pulmonary patients) is harmless or detrimental.

还原应激被定义为细胞谷胱甘肽/谷胱甘肽二硫化物和 NADH/NAD ⁺比率持续增加的条件。还原应激正在成为多种疾病状态下的重要病理生理事件，与氧化应激一样有害。还原应激的发生已在多种心肌病中得到证实，并且是重要的病理生理学因素，特别是在冠状动脉疾病和心肌梗塞中。在大多数情况下，由于自噬缺陷导致转录因子 Nrf2（抗氧化反应的主要调节因子）过度激活，可能导致还原应激。此外，高血糖诱导的多元醇途径激活可导致 NADH/NAD ⁺比率增加，这可能会通过增强胱硫醚 β-合酶的活性转化为硫化氢水平的增加，从而通过抑制线粒体复合物来加剧还原应激I. 还原应激可能是对抗癌症的潜在武器，引发肿瘤细胞凋亡，也可能是癌症的盟友，促进肿瘤细胞增殖并使肿瘤细胞对活性氧诱导药物产生耐药性。在非癌症病理状态下，还原应激肯定是有害的，但矛盾的是，NADPH 氧化酶 4 活性过高会导致活性氧过度产生。面对多种心脏病中还原应激的发生的记录，有关骨骼肌组织中还原应激的发生和影响的信息要少得多。 在本综述中，我们描述了心脏还原应激研究的相关结果，并回顾了通过实验记录还原应激的骨骼肌状况以及还原应激可能具有尚未认识到的病理生理学作用的骨骼肌状况。确定还原性应激是否在骨骼肌中具有（病理）生理作用，有望有助于回答普通人群、运动员和大量患者（例如心脏病、肌肉减少症、营养不良、肌病、癌症和癌症患者）补充抗氧化剂是否有益的问题。支气管肺疾病患者）是无害或有害的。