NaHS protects brain, heart, and lungs as remote organs from renal ischemia/reperfusion-induced oxidative stress in male and female rats

Acute Kidney Injury (AKI) is frequently observed in hospitalized patients in intensive care units, often caused by renal ischemia-reperfusion injury (IRI). IRI disrupts the function of various ‘remote organs’ such as the lungs, pancreas, intestine, liver, heart, and brain through inflammation, oxidative stress, apoptosis, leukocyte infiltration, and increased urea and creatinine levels. Gender differences in renal IRI-induced injury are noted. H2S, an endogenous gaseous modulator, shows potential in vasodilation, bronchodilation, and hypotension and can regulate apoptosis, inflammation, angiogenesis, metabolism, and oxidative stress. This study aims to investigate the protective effects of NaHS on brain, heart, and lung injuries following renal IR and to assess the oxidative system status as a potential mechanism in male and female rats. Forty-eight Wistar rats were randomly divided into eight groups (n = 6): Control/Saline, Sham/Saline, IR/Saline, and IR/NaHS in both sexes. Forty-five minutes of bilateral renal ischemia followed by 24-hour reperfusion was induced in the IR groups. NaHS (100µM/Kg, IP) was administered 10 min before clamp release in treated groups. BUN, SCr, BUN/SCr, albuminuria, histopathology, and oxidative stress biomarkers of the brain, heart, and lung were assessed as remote organs. IR increased serum markers of renal function, albuminuria, malondialdehyde levels, and tissue injury scores while reducing nitrite levels and superoxide dismutase and glutathione peroxidase activities. NaHS treatment reversed the adverse effects of IR in remote organs in both sexes, although it showed limited improvement in renal function. Our findings demonstrate that NaHS has a beneficial effect on remote organ injury following renal IR by mitigating oxidative stress, with noted tissue-specific and gender-specific differences in response. These findings suggest NaHS as a potential therapeutic agent for mitigating multi-organ injury after renal IR, with effects varying by tissue and gender.