PMID- 30105650 OWN - NLM STAT- MEDLINE DCOM- 20190812 LR - 20190812 IS - 1559-1174 (Electronic) IS - 1535-1084 (Linking) VI - 20 IP - 4 DP - 2018 Dec TI - Neuroprotective Effect of Hydrogen Sulfide in Hyperhomocysteinemia Is Mediated Through Antioxidant Action Involving Nrf2. PG - 475-490 LID - 10.1007/s12017-018-8505-y [doi] AB - Homocysteine (Hcy) is a sulfur-containing amino acid derived from methionine metabolism. Elevated plasma Hcy levels (> 15 microM) result in a condition called hyperhomocysteinemia (HHcy), which is an independent risk factor in the development of various neurodegenerative disorders. Reactive oxygen species (ROS) produced by auto-oxidation of Hcy have been implicated in HHcy-associated neurological conditions. Hydrogen sulfide (H(2)S) is emerging as a potent neuroprotective and neuromodulator molecule. The present study was aimed to evaluate the ability of NaHS (a source of H(2)S) to attenuate Hcy-induced oxidative stress and altered antioxidant status in animals subjected to HHcy. Impaired cognitive functions assessed by Y-maze and elevated plus maze in Hcy-treated animals were reversed on NaHS administration. Increased levels of ROS, lipid peroxidation, protein carbonyls, and 4-hydroxynonenal (4-HNE)-modified proteins were observed in the cortex and hippocampus of Hcy-treated animals suggesting accentuated oxidative stress. This increase in Hcy-induced oxidative stress was reversed following NaHS supplementation. GSH/GSSG ratio, activity of antioxidant enzymes viz; superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase were decreased in Hcy-treated animals. NaHS supplementation, on the otherhand, restored redox ratio and activity of antioxidant enzymes in the brains of animals with HHcy. Further, NaHS administration normalized nuclear factor erythroid 2-related factor 2 expression and acetylcholinesterase (AChE) activity in the brain of Hcy-treated animals. Histopathological studies using cresyl violet indicated higher number of pyknotic neurons in the cortex and hippocampus of HHcy animals, which were reversed by NaHS administration. The results clearly demonstrate that NaHS treatment significantly ameliorates Hcy-induced cognitive impairment by attenuating oxidative stress, improving antioxidant status, and modulating AChE activity thereby suggesting potential of H(2)S as a therapeutic molecule. FAU - Kumar, Mohit AU - Kumar M AD - Department of Biochemistry, Basic Medical Science Block-II, Sector-25, Panjab University, Chandigarh, 160014, India. FAU - Sandhir, Rajat AU - Sandhir R AD - Department of Biochemistry, Basic Medical Science Block-II, Sector-25, Panjab University, Chandigarh, 160014, India. sandhir@pu.ac.in. LA - eng GR - BT/361/NE/TBP/2012/Department of Bio-Technology (DBT), Govt. of India, New Delhi/International GR - [F.17-7(J)/2004(SA-1)]/University Grants Commission (UGC), New Delhi/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180813 PL - United States TA - Neuromolecular Med JT - Neuromolecular medicine JID - 101135365 RN - 0 (Antioxidants) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Neuroprotective Agents) RN - 0 (Nfe2l2 protein, rat) RN - 0 (Reactive Oxygen Species) RN - 0LVT1QZ0BA (Homocysteine) RN - EC 1.- (Oxidoreductases) RN - EC 3.1.1.7 (Acetylcholinesterase) RN - YY9FVM7NSN (Hydrogen Sulfide) MH - Acetylcholinesterase/metabolism MH - Animals MH - Antioxidants/*pharmacology MH - Cerebral Cortex/*drug effects/metabolism MH - Cognition Disorders/etiology/*prevention & control MH - Hippocampus/*drug effects/metabolism MH - Homocysteine/toxicity MH - Hydrogen Sulfide/*pharmacology/therapeutic use MH - Hyperhomocysteinemia/*drug therapy/metabolism/psychology MH - Lipid Peroxidation/drug effects MH - Male MH - Maze Learning/drug effects MH - NF-E2-Related Factor 2/biosynthesis/genetics/*physiology MH - Neuroprotective Agents/*pharmacology MH - Oxidation-Reduction MH - Oxidative Stress MH - Oxidoreductases/metabolism MH - Protein Carbonylation/drug effects MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism OTO - NOTNLM OT - Antioxidant OT - Homocysteine OT - Hydrogen sulfide OT - Memory OT - Nrf2 OT - Oxidative stress EDAT- 2018/08/15 06:00 MHDA- 2019/08/14 06:00 CRDT- 2018/08/15 06:00 PHST- 2018/03/06 00:00 [received] PHST- 2018/08/06 00:00 [accepted] PHST- 2018/08/15 06:00 [pubmed] PHST- 2019/08/14 06:00 [medline] PHST- 2018/08/15 06:00 [entrez] AID - 10.1007/s12017-018-8505-y [pii] AID - 10.1007/s12017-018-8505-y [doi] PST - ppublish SO - Neuromolecular Med. 2018 Dec;20(4):475-490. doi: 10.1007/s12017-018-8505-y. Epub 2018 Aug 13.