This study evaluates the effects produced by H2S donor; sodium hydrosulfide (NaHS), in a renal ischemia/reperfusion (IR) rat model and assesses the possible mediating role of nitric oxide (NO) in these H2S' effects.
Background: For several centuries, hydrogen sulfide (H₂S) had been known to be a highly toxic agent. Recent studies, however, indicated that apart from NO and CO, H₂S is the third "gasotransmitter" involved in the regulation of various physiological functions. Nevertheless, its impact on renal IR injury remains unclear.
Methods: Rats were randomly divided into three groups: sham control; renal IR; and renal IR+NaHS groups.NaHS (100 µmol/kg, ip) was administered 30 min prior to the induction of renal ischemia.
Results: NaHS was found to attenuate significantly the IR-induced elevations in the serum levels of urea, creatinine and tumor necrosis factor α (TNF-α) as compared with IR group. NaHS also significantly compensated the deficits in the total antioxidant capacities (TAC) and lowered the elevated malondialdehyde (MDA) levels observed with renal IR in renal, hepatic, pulmonary, and cardiac tissues. Furthermore, NaHS pretreatment down-regulated the renal IR-induced over-expression of inducible nitric oxide synthase (iNOS) and up-regulated the IR-induced suppression of endothelial nitric oxide synthase (eNOS). The loss of normal architecture, hemorrhage, and inflammatory cells infiltration detected by histopathological examination of renal, hepatic, pulmonary, and cardiac tissues in IR rats were markedly ameliorated by pre-ischemic NaHS treatment.
Conclusion: NaHS protects against the effects of renal IR injury by acting primarily through a decrease in both pro-inflammatory cytokines and iNOS expression as well as through up-regulation of the eNOS pathway. Furthermore, H₂S has a powerful anti-oxidant and anti-apoptotic effects (Tab. 2, Fig. 6, Ref. 45).
Keywords: Hydrogen sulfide; ischemia/reperfusion injury; malondialdehyde; nitric oxide; total antioxidant capacities.; tumor necrosis factor α.