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Mitochondrion. 2020 Jan;50:158-169. doi: 10.1016/j.mito.2019.11.004. Epub 2019 Nov 18.

Hydrogen sulfide attenuates hyperhomocysteinemia-induced mitochondrial dysfunctions in brain.

Author information

1
Department of Biochemistry, Basic Medical Science Block-II, Panjab University, Chandigarh 160014, India.
2
Department of Biochemistry, Basic Medical Science Block-II, Panjab University, Chandigarh 160014, India. Electronic address: sandhir@pu.ac.in.

Abstract

Hyperhomocysteinemia (HHcy) has been implicated in the 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 decreased 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 H2S releasing drugs may be a novel therapeutic approach to treat HHcy associated neurological disorders.

KEYWORDS:

Homocysteine; Hydrogen sulfide; Mitochondria; Oxidative stress; Oxygen consumption rate

PMID:
31751655
DOI:
10.1016/j.mito.2019.11.004

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