P30 NAHS and STS treatment in ischemia–reperfusion injury in rats

Abstract

Ischemia–reperfusion injury (IRI) is a major cause of renal transplant dysfunction. Hydrogen sulfide (H 2 S) can attenuate IRI in mice by metabolic suppression and vasodilatory, anti-inflammatory and anti-oxidant effects. We now investigated the protective properties of H 2 S (sodium hydrosulfide (NaHS)) and its endogenous donor thiosulfate (sodium thiosulfate (STS)) in unilateral IRI in rats and in isolated rat kidneys. In vivo , rats underwent 35 min of unilateral warm ischemia (WI) and received vehicle, NaHS (5.6 mg/kg/day) or STS (1 g/kg/day) via intra-peritoneal injections twice daily from 48 h before WI until sacrifice at 24 or 96 h after reperfusion ( n = 7/group). Kidneys were studied for tubular epithelial damage (KIM-1), macrophages (ED1), early fibrotic changes (alphaSMA) and oxidative stress (MDA). Ex vivo , kidneys were exposed to 1 mM NaHS ( n = 4) for 40 min and O 2 consumption and ATP were compared to controls ( n = 3). Immunohistochemistry (KIM-1, ED1, alphaSMA) showed no benefit from NaHS or STS treatment. Also, at mRNA level no differences were found (KIM-1, alphaSMA). MDA levels were the same for all treatment groups. Ex vivo , H 2 S reduced O 2 consumption and ATP both by over 50% ( p < 0.05). In conclusion, in vivo , NaHS and STS treatment do not protect from IRI in rats. Ex vivo data however, show metabolic suppression in isolated rat kidneys. These data indicate a possible role for H 2 S as a treatment modality for ex vivo kidney transplant protection.