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OBJECTIVES: This study evaluates the effects produced by H 2 S donor; sodium hydrosulfi de (NaHS), in a renal ischemia/reperfusion (IR) rat model and assesses the possible mediating role of nitric oxide (NO) in these H 2 S' effects. BACKGROUND: For several centuries, hydrogen sulfi de (H 2 S) had been known to be a highly toxic agent. Recent studies, however, indicated that apart from NO and CO, H 2 S 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 signifi cantly 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 signifi cantly compensated the defi cits 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 infl ammatory cells infi ltration 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-infl ammatory cytokines and iNOS expression as well as through up-regulation of the eNOS pathway. Furthermore, H 2 S has a powerful anti-oxidant and anti-apoptotic effects (Tab. 2, Fig. 6, Ref. 45). Text in PDF www.elis.sk. KEY WORDS:Hydrogen sulfi de, ischemia/reperfusion injury, nitric oxide, tumor necrosis factor α, malondialdehyde, total antioxidant capacities.

Although its role and importance is less well studied, carbon monoxide (CO) has been identifi ed as the second gasotransmitter in the GI tract. This study was performed to investigate the effect of modifying the endogenous CO production by altering heme oxygenase (HO) activity either by induction through hemin administration or inhibition by zinc mesoporphyrin administration on gastric secretion and ulceration induced by either cold restraint stress (CRS) or indomethacin (IND) treatment in adult male albino rats. Our results revealed that hemin signifi cantly increased HO-1 levels with an increase in carboxyhemoglobin (COHb) level while zinc mesoporphyrin signifi cantly decreased HO-1 levels with a decrease in COHb level in all groups. Hemin pretreatment signifi cantly attenuated the gastric mucosal lesions induced by CRS and IND administration, which was accompanied by signifi cant reduction in free and total acidity of gastric secretion, decreased proteolytic activity and marked attenuation of lipid peroxidation inspite of decreased NO and PGE 2 levels. On the other hand, Inhibition of HO-1 activity by zinc mesoporphyrin prevented most of the effects caused by hemin administration except for its similar reduction in gastric mucosal NO and PGE 2 levels. On conclusion, Hemin exerts a protective effect against CRS and IND-induced gastric ulcers possibly via inducing HO-1 and increasing endogenous production of CO (Tab. 2, Fig. 4, Ref. 75). Text in PDF www.elis.sk.