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

• Published in: Laboratory investigation 2008-10, Vol.88 (10), p.1038-1048
• Main Authors: Tripatara, Pinpat, SA Patel, Nimesh, Collino, Massimo, Gallicchio, Margherita, Kieswich, Julius, Castiglia, Sara, Benetti, Elisa, Stewart, Keith N, Brown, Paul AJ, Yaqoob, Mohammed M, Fantozzi, Roberto, Thiemermann, Christoph
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - metabolism; Apoptosis - physiology; Biological and medical sciences; Biotechnology; Cystathionine gamma-Lyase - metabolism; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Hydrogen Sulfide - metabolism; Investigative techniques, diagnostic techniques (general aspects); Kidney - pathology; Kidney - physiopathology; Laboratory Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Pathology; Rats; Rats, Wistar; Recovery of Function - physiology; Reperfusion Injury - pathology; Reperfusion Injury - physiopathology; research-article
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.2008.73

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 γ -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-κB. 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-κB-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.