PMID- 19474193
OWN - NLM
STAT- MEDLINE
DCOM- 20090827
LR  - 20220316
IS  - 1522-1466 (Electronic)
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 297
IP  - 2
DP  - 2009 Aug
TI  - Hydrogen sulfide ameliorates hyperhomocysteinemia-associated chronic renal 
      failure.
PG  - F410-9
LID - 10.1152/ajprenal.00145.2009 [doi]
AB  - 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.
FAU - Sen, Utpal
AU  - Sen U
AD  - Dept. of Physiology & Biophysics, Univ. of Louisville School of Medicine, 500 S. 
      Preston St., Louisville, KY 40202, USA. u0sen001@louisville.edu
FAU - Basu, Poulami
AU  - Basu P
FAU - Abe, Oluwasegun A
AU  - Abe OA
FAU - Givvimani, Srikanth
AU  - Givvimani S
FAU - Tyagi, Neetu
AU  - Tyagi N
FAU - Metreveli, Naira
AU  - Metreveli N
FAU - Shah, Karan S
AU  - Shah KS
FAU - Passmore, John C
AU  - Passmore JC
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - R01 HL074185/HL/NHLBI NIH HHS/United States
GR  - R01 HL071010/HL/NHLBI NIH HHS/United States
GR  - R01 NS051568/NS/NINDS NIH HHS/United States
GR  - R01 HL088012/HL/NHLBI NIH HHS/United States
GR  - NS-51568/NS/NINDS NIH HHS/United States
GR  - HL-74185/HL/NHLBI NIH HHS/United States
GR  - HL-88012/HL/NHLBI NIH HHS/United States
GR  - HL-71010/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090527
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Antioxidants)
RN  - 0 (Desmin)
RN  - 0 (Membrane Proteins)
RN  - 0 (Sulfides)
RN  - 0 (nephrin)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 11062-77-4 (Superoxides)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.24 (Mmp2 protein, mouse)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.35 (Mmp9 protein, mouse)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
RN  - FWU2KQ177W (sodium bisulfide)
RN  - GAN16C9B8O (Glutathione)
RN  - ULW86O013H (Glutathione Disulfide)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cystathionine beta-Synthase/genetics/metabolism
MH  - Desmin/metabolism
MH  - Disease Models, Animal
MH  - Glutathione/metabolism
MH  - Glutathione Disulfide/metabolism
MH  - Homocysteine/blood
MH  - Hydrogen Sulfide/blood/*metabolism
MH  - Hyperhomocysteinemia/*drug therapy/genetics/metabolism
MH  - Kidney/*drug effects/metabolism/pathology
MH  - Kidney Failure, Chronic/genetics/metabolism/*prevention & control
MH  - Male
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nephrectomy
MH  - Oxidative Stress/drug effects
MH  - Proteinuria/metabolism/prevention & control
MH  - Sulfides/metabolism/*pharmacology
MH  - Superoxides/metabolism
PMC - PMC2724247
EDAT- 2009/05/29 09:00
MHDA- 2009/08/28 09:00
PMCR- 2010/08/01
CRDT- 2009/05/29 09:00
PHST- 2009/05/29 09:00 [entrez]
PHST- 2009/05/29 09:00 [pubmed]
PHST- 2009/08/28 09:00 [medline]
PHST- 2010/08/01 00:00 [pmc-release]
AID - 00145.2009 [pii]
AID - F-00145-2009 [pii]
AID - 10.1152/ajprenal.00145.2009 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2009 Aug;297(2):F410-9. doi: 
      10.1152/ajprenal.00145.2009. Epub 2009 May 27.