Downregulation of the renal and hepatic hydrogen sulfide (H2S)-producing enzymes and capacity in chronic kidney disease
- 29 October 2011
- journal article
- research article
- Published by Oxford University Press (OUP) in Nephrology Dialysis Transplantation
- Vol. 27 (2), 498-504
- https://doi.org/10.1093/ndt/gfr560
Abstract
Oxidative stress and inflammation are constant features and major mediators of progression and cardiovascular complications of chronic kidney disease (CKD). Hydrogen sulfide (H(2)S) is an endogenous signaling gas, which possesses potent anti-oxidant, anti-inflammatory, anti-hypertensive and other regulatory functions. H(2)S is produced by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (MST). Plasma H(2)S is reduced in humans with hypertension, atherosclerosis and end-stage renal disease (ESRD). Atherosclerosis, hypertension and ischemia/reperfusion-induced acute kidney injury are associated with and, in part, mediated by diminished tissue H(2)S in experimental animals. Expression of the H(2)S-producing enzymes is reduced in the circulating leukocytes of patients with ESRD. However, the effect of CKD on expression of H(2)S-producing enzymes in the diseased kidney and other tissues is unknown and was studied here. Subgroups of rats were subjected to 5/6 nephrectomy or sham operation and observed for 6-12 weeks. Expression of H(2)S-producing enzymes and H(2)S-producing capacity was measured in kidney, liver and brain tissues. The CKD group exhibited oxidative stress and significant reduction of plasma H(2)S concentration. This was associated with marked reduction of H(2)S-producing capacity of the kidney and liver, marked downregulation of CBS, CSE and MST in the kidney and of CBS and CSE expression in the liver. However, expression of H(2)S-producing enzymes in the brain was not significantly altered in CKD rats. CKD is associated with significant reduction in plasma H(2)S concentration, diminished remnant kidney and liver tissue H(2)S-producing capacity and downregulation of the H(2)S-producing enzymes. Given the potent anti-oxidant, anti-inflammatory and cytoprotective properties of H(2)S, its deficiency may contribute to progression of CKD and the associated complications.Keywords
This publication has 57 references indexed in Scilit:
- Niacin ameliorates oxidative stress, inflammation, proteinuria, and hypertension in rats with chronic renal failureAmerican Journal of Physiology-Renal Physiology, 2009
- Melatonin ameliorates oxidative stress, inflammation, proteinuria, and progression of renal damage in rats with renal mass reductionAmerican Journal of Physiology-Renal Physiology, 2008
- Chronic inhibition of nuclear factor-κB attenuates renal injury in the 5/6 renal ablation modelAmerican Journal of Physiology-Renal Physiology, 2007
- Spontaneous leukocyte activation and oxygen-free radical generation in end-stage renal diseaseKidney International, 2007
- Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetesJCI Insight, 2006
- Oxidative Stress and Antioxidant Treatment in Hypertension and the Associated Renal DamageAmerican Journal of Nephrology, 2005
- Oxidative stress in uremia: Nature, mechanisms, and potential consequencesSeminars in Nephrology, 2004
- Roles of oxidative stress and antioxidant therapy in chronic kidney disease and hypertensionCurrent Opinion in Nephrology and Hypertension, 2004
- Oxidative stress in uremiaCurrent Opinion in Nephrology and Hypertension, 2003
- The elephant in uremia: Oxidant stress as a unifying concept of cardiovascular disease in uremiaKidney International, 2002