Generation of endogenous hydrogen sulfide by cystathionine gamma-lyase limits renal ischemia/reperfusion injury and dysfunction.

Abstract

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.

• Authors: Pinpat Tripatara, Nimesh S A Patel, Massimo Collino, Margherita Gallicchio, Julius Kieswich, Sara Castiglia, Elisa Benetti, Keith N Stewart, Paul A J Brown, Mohammed M Yaqoob, Roberto Fantozzi, Christoph Thiemermann
• Journal: Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 88 Issue 10 Pg. 1038-48 (Oct 2008) ISSN: 1530-0307 [Electronic] United States
• PMID: 18679378 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cystathionine gamma-Lyase
• Hydrogen Sulfide

Topics

• Animals
• Anti-Inflammatory Agents (metabolism)
• Apoptosis (physiology)
• Cystathionine gamma-Lyase (metabolism)
• Disease Models, Animal
• Hydrogen Sulfide (metabolism)
• Kidney (pathology, physiopathology)
• Male
• Rats
• Rats, Wistar
• Recovery of Function (physiology)
• Reperfusion Injury (pathology, physiopathology)