Hyperhomocysteinemia (HHcy) has been implicated in development of neurodegenerative conditions and mild cognitive disorders. Mitochondrial dysfunctions are the major mechanisms involved in homocysteine (Hcy)-induced neurotoxicity. Although, hydrogen sulfide has been reported as potent antioxidant, its effects on Hcy-induced mitochondrial dysfunctions have not been studied. Therefore, the present study has been designed to evaluate the protective effect of NaHS on Hcy-induced mitochondrial dysfunctions in brain. NaHS supplementation decreased reactive oxygen species and nitrite levels in the cortex and hippocampus of animals with HHcy. NaHS supplementation increased the activity of mitochondrial electron transport chain components; NADH dehydrogenase, cytochrome c oxidase and F0-F1 ATPase in the cortex and hippocampus of HHcy animals along with in-gel activity of complex I - complex V in the mitochondria isolated from the cortex and hippocampus of HHcy animals. Moreover, NaHS supplementation also increased the mitochondrial complex I, II and IV mediated oxygen consumption rate in Hcy treated mitochondria. NaHS administration prevented the Hcy-induced mitochondrial damage as suggested by the deceased mitochondrial swelling in the cortex and hippocampus of HHcy animals. NaHS supplementation decreased the activity of lactate dehydrogenase isozymes (1-5) in the brain regions of HHcy animals. The expression of protein kinase c δ was also decreased in the brain regions of HHcy animals following NaHS supplementation. This was accompanied by reduced activity of caspase-3 indicating anti-apoptotic effect of H2S. Taken together, the findings suggest that H2S supplementation ameliorates Hcy-induced oxidative stress and mitochondrial dysfunctions suggesting it be a novel therapeutic to treat HHcy associated neurological disorders.

中文翻译：

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硫化氢减轻高同型半胱氨酸血症诱导的脑线粒体功能障碍

高同型半胱氨酸血症 (HHcy) 与神经退行性疾病和轻度认知障碍的发展有关。线粒体功能障碍是参与同型半胱氨酸 (Hcy) 诱导的神经毒性的主要机制。虽然，硫化氢已被报道为有效的抗氧化剂，但尚未研究其对 Hcy 诱导的线粒体功能障碍的影响。因此，本研究旨在评估 NaHS 对 Hcy 诱导的大脑线粒体功能障碍的保护作用。NaHS 补充剂降低了 HHcy 动物皮层和海马中的活性氧和亚硝酸盐水平。NaHS 补充增加了线粒体电子传递链组件的活性；NADH脱氢酶，HHcy 动物皮层和海马中的细胞色素 c 氧化酶和 F0-F1 ATPase 以及从 HHcy 动物皮层和海马分离的线粒体中复合物 I - 复合物 V 的凝胶内活性。此外，在 Hcy 处理的线粒体中，NaHS 补充剂还增加了线粒体复合物 I、II 和 IV 介导的耗氧率。正如 HHcy 动物的皮层和海马中已死亡的线粒体肿胀所表明的那样，NaHS 给药可防止 Hcy 诱导的线粒体损伤。NaHS 补充剂降低了 HHcy 动物大脑区域中乳酸脱氢酶同工酶 (1-5) 的活性。补充 NaHS 后，HHcy 动物大脑区域中蛋白激酶 c δ 的表达也降低。这伴随着 caspase-3 活性的降低，表明 H2S 的抗细胞凋亡作用。综上所述，研究结果表明，H2S 补充剂可改善 Hcy 诱导的氧化应激和线粒体功能障碍，表明它是一种治疗 HHcy 相关神经系统疾病的新疗法。