Cerebroprotective effects of hydrogen sulfide in homocysteine-induced neurovascular permeability: Involvement of oxidative stress, arginase, and matrix metalloproteinase-9.

Abstract

An elevated level of homocysteine (Hcy) leads to hyperhomocysteinemia (HHcy), which results in vascular dysfunction and pathological conditions identical to stroke symptoms. Hcy increases oxidative stress and leads to increase in blood-brain barrierpermeability and leakage. Hydrogen sulfide (H2 S) production during the metabolism of Hcy has a cerebroprotective effect, although its effectiveness in Hcy-induced neurodegeneration and neurovascular permeability is less explored. Therefore, the current study was designed to perceive the neuroprotective effect of exogenous H 2 S against HHcy, a cause of neurodegeneration. To test this hypothesis, we used four groups of mice: control, Hcy, control + sodium hydrosulfide hydrate (NaHS), and Hcy + NaHS, and an HHcy mice model in Swiss albino mice by giving a dose of 1.8 g of dl-Hcy/L in drinking for 8-10 weeks. Mice that have 30 µmol/L Hcy were taken for the study, and a H 2 S supplementation of 20 μmol/L was given for 8 weeks to all groups of mice. HHcy results in the rise of the levels of superoxide and nitrite, although a concomitant decrease in the level of superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and arginase in oxidative stress and a concomitant decrease in the endogenous level of H 2 S. AlthoughH 2 S supplementation ameliorated, the effect of HHcy and the levels of H 2 S returned to the average level in HHcy animals supplemented with H 2 S. Interestingly, H 2 S supplementation ameliorated neurovascular remodeling and neurodegeneration. Thus, our study suggested that H 2 S could be a beneficial therapeutic candidate for the treatment of Hcy-associated neurodegeneration, such as stroke and neurovascular disorders.