Generation of endogenous hydrogen sulfide by cystathionine gamma-lyase limits renal ischemia/reperfusion injury and dysfunction.
The generation of endogenous hydrogen sulfide may either limit or contribute to the degree of tissue injury caused by ischemia/reperfusion. A total of 74 male Wistar rats were used to investigate the effects of endogenous and exogenous hydrogen sulfide in renal ischemia/reperfusion. Administration of the irreversible cystathionine gamma-lyase (CSE) inhibitor, dL-propargylglycine, prevented the recovery of renal function after 45 min ischemia and 72 h reperfusion. The hydrogen sulfide donor sodium hydrosulfide attenuated the (renal, tubular, and glomerular) dysfunction and injury caused by 45 min ischemia and 6 h reperfusion. Western blot analysis of kidneys taken at 30 min reperfusion showed that sodium hydrosulfide significantly attenuated phosphorylation of mitogen-activated protein kinases (p-38, c-JUN N-terminal protein kinase 1/2, and extracellular signal-regulated kinase 1/2) and activation of nuclear factor-kappaB. At 6 h reperfusion, sodium hydrosulfide significantly attenuated the histological score for acute tubular necrosis, the activation of caspase-3 and Bid, the decline in the expression of anti-apoptotic Bcl-2, and the expression of nuclear factor-kappaB-dependent proteins (inducible nitric oxide synthase, cyclo-oxygenase-2, and intercellular adhesion molecule-1). These findings suggest that (1) the synthesis of endogenous hydrogen sulfide by CSE is essential to protect the kidney against ischemia/reperfusion injury and dysfunction and aids in the recovery of renal function following ischemia/reperfusion, (2) hydrogen sulfide generated by sodium hydrosulfide reduces ischemia/reperfusion injury and dysfunction, and morphological changes of the kidney, and (3) the observed protective effects of hydrogen sulfide are due to both anti-apoptotic and anti-inflammatory effects.
Tripatara
Pinpat
P
Centre for Translational Medicine and Therapeutics, William Harvey Research Institute, St Bartholomew's and The Royal London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Patel
Nimesh S A
NS
Collino
Massimo
M
Gallicchio
Margherita
M
Kieswich
Julius
J
Castiglia
Sara
S
Benetti
Elisa
E
Stewart
Keith N
KN
Brown
Paul A J
PA
Yaqoob
Mohammed M
MM
Fantozzi
Roberto
R
Thiemermann
Christoph
C
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D003542:Cystathionine gamma-Lyase / Q000378:metabolism*; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*
D000893:Anti-Inflammatory Agents; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide