H₂S Donor NaHS Changes the Production of Endogenous H₂S and NO in D‐Galactose‐Induced Accelerated Ageing

Abstract

Aims. The study was designed to explore whether hydrogen sulphide (H2S) and nitric oxide (NO) generation changed in D-galactose- (D-gal-) induced ageing, the possible effects of exogenous H2S supplementation, and related mechanisms. Results. In D-gal-induced senescent mice, both H2S and NO levels in the heart, liver, and kidney tissues were decreased significantly. A similar trend was observed in D-gal-challenged human umbilical vein endothelial cells (HUVECs). Sustained H2S donor (NaHS) treatment for 2 months elevated H2S and NO levels in these mice, and during this period, the D-gal-induced senescent phenotype was reversed. The protective effect of NaHS is associated with a decrease in reactive oxygen species levels and an increase in antioxidants, such as glutathione, and superoxide dismutase and glutathione peroxidase activities. Increased expression of the H2S-producing enzymes cystathionine γ-lyase (CSE) and cystathionine-β-synthase (CBS) in the heart, liver, and kidney tissues was observed in the NaHS-treated groups. NaHS supplementation also significantly postponed D-gal-induced HUVEC senescence. Conclusions. Endogenous hydrogen sulphide production in both ageing mice and endothelial cells is insufficient. Exogenous H2S can partially rescue ageing-related dysfunction by inducing endogenous H2S and NO production and reducing oxidative stress. Restoring endogenous H2S production may contribute to healthy ageing, and H2S may have antiageing effects.

Effects of d‐galactose‐induced ageing on the heart and its potential interventions

“…) . In support of this finding, decreased levels of endogenous antioxidant enzymes such as SOD , glutathione peroxidase , and reduced glutathione levels were demonstrated in d ‐galactose‐treated rats and mice. In addition, increased DHE fluorescence staining, decreased endogenous hydrogen sulphide production, endogenous hydrogen sulphide producing enzyme cystathionine γ‐lyase (CSE), and nitric oxide (NO) , and decreased haem oxygenase‐1 (HO‐1) were also found in d ‐galactose‐induced cardiac ageing models.…”

“…Administration of d ‐galactose in mice and rats at the age of 2–5 months old, at the dose of 60–150 mg/kg/day, for 6–8 weeks, can increase senescence markers in cardiac tissue . For in vitro study, 5 g/l of d ‐galactose was added to neonatal SD rat cardiomyocytes for 48 hr to induce ageing .…”

“…Furthermore, the mechanisms involved in senescence usually include the p53 or p16 tumour suppressor pathways. Both p53 and p21 expressions were up‐regulated in the d ‐galactose‐induced ageing mice model . Senescent cells accumulate in the cardiac tissues, leading to reduced regenerative capacity and increased low‐grade inflammation, subsequently inducing ageing and age‐related diseases.…”

“…Evidence shows that d ‐galactose administration increased expression of oxidative stress and decreased expression of antioxidants . The doses of d ‐galactose involved varied between 50 and 400 mg/kg/day, and duration of the studies was from 6 to 8 weeks . Although there are three different metabolic pathways specific to d ‐galactose in the body , the main pathway is the Leloir pathway.…”

Mechanisms of Hydrogen Sulfide against the Progression of Severe Alzheimer’s Disease in Transgenic Mice at Different Ages

“…The endogenous micromolar levels of H 2 S have been measured in the brain, blood and peripheral organs of rats, humans, and bovine and production differs considerably between the various mammalian species [11]; moreover, levels of H 2 S decrease with ageing [12]. Endogenous H 2 S is generated from cysteine metabolism through 2 enzymes: cystathionine-β-synthase and cystathionine-γ-lyase whose productions are mainly in the brain for the former and largely in the cardiovascular system for the latter [13,14].…”