JOURNAL ARTICLE

Hydrogen sulfide ameliorates hyperhomocysteinemia-associated chronic renal failure

Utpal Sen, Poulami Basu, Oluwasegun A Abe, Srikanth Givvimani, Neetu Tyagi, Naira Metreveli, Karan S Shah, John C Passmore, Suresh C Tyagi
American Journal of Physiology. Renal Physiology 2009, 297 (2): F410-9
19474193
Elevated level of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), is associated with end-stage renal diseases. Hcy metabolizes in the body to produce hydrogen sulfide (H(2)S), and studies have demonstrated a protective role of H(2)S in end-stage organ failure. However, the role of H(2)S in HHcy-associated renal diseases is unclear. The present study was aimed to determine the role of H(2)S in HHcy-associated renal damage. Cystathionine-beta-synthase heterozygous (CBS+/-) and wild-type (WT, C57BL/6J) mice with two kidney (2-K) were used in this study and supplemented with or without NaHS (30 micromol/l, H(2)S donor) in the drinking water. To expedite the HHcy-associated glomerular damage, uninephrectomized (1-K) CBS(+/-) and 1-K WT mice were also used with or without NaHS supplementation. Plasma Hcy levels were elevated in CBS(+/-) 2-K and 1-K and WT 1-K mice along with increased proteinuria, whereas, plasma levels of H(2)S were attenuated in these groups compared with WT 2-K mice. Interestingly, H(2)S supplementation increased plasma H(2)S level and normalized the urinary protein secretion in the similar groups of animals as above. Increased activity of matrix metalloproteinase (MMP)-2 and -9 and apoptotic cells were observed in the renal cortical tissues of CBS(+/-) 2-K and 1-K and WT 1-K mice; however, H(2)S prevented apoptotic cell death and normalized increased MMP activities. Increased expression of desmin and downregulation of nephrin in the cortical tissue of CBS(+/-) 2-K and 1-K and WT 1-K mice were ameliorated with H(2)S supplementation. Additionally, in the kidney tissues of CBS(+/-) 2-K and 1-K and WT 1-K mice, increased superoxide (O(2)(*-)) production and reduced glutathione (GSH)-to-oxidized glutathione (GSSG) ratio were normalized with exogenous H(2)S supplementation. These results demonstrate that HHcy-associated renal damage is related to decreased endogenous H(2)S generation in the body. Additionally, here we demonstrate with evidence that H(2)S supplementation prevents HHcy-associated renal damage, in part, through its antioxidant properties.

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