Hydrogen sulfide metabolism and its role in kidney function in a rat model of chronic kidney disease

Abstract

Chronic kidney disease (CKD) is an ongoing global problem. It is correlated with a substantial increase in mortality and morbidity. Although, hydrogen sulfide (H2S) plays an important role in the physiological and pathological processes in the kidney, the influence of CKD on the enzymatic synthesis and utilization of H2S in the kidney is unclear. The aim of this study was to evaluate the activity of H2S-producing enzymes (сystathionine gamma-lyase, cystathionine beta-synthase and cysteine aminotransferase) and the content of H2S in rats with CKD, and to establish the relationship between these parameters and markers of the functional state of the kidneys. Material and methods. CKD in rats was induced by 5/6 nephrectomy of the contralateral kidney. H2S regulation was examined in post-nuclear kidney homogenates by measuring H2S levels and cystathionine gamma-lyase, cystathionine beta-synthase, and cysteine aminotransferase activity using spectrophotometric methods. Functional and biochemical measurements were monitored after water load (5% of body mass). Results. CKD in rats was associated with defects in H2S metabolism in rat kidneys. The activity of H2Sproducing enzymes decreased by 28.3-34.2% (p<0.05), the rate of utilization of exogenous H2S in the kidneys increased by 34.3% (p<0.05), and the content of H2S was reduced by 35.8% (p<0.05) in comparison with a control group. A progressive loss of kidney function (tubular and glomerular disorders) is closely correlated with the content of H2S in the kidneys. Conclusions. The H2S system in kidneys may be an important metabolic target, which can influence the efficacy of treatments to improve the functional state of kidneys in CKD.