The effects of CORM3 or NaHS on the oxidative stress caused by chronic kidney disease in rats: potential interaction between CO and H 2 S signaling pathway

Neurotoxicity is implicated as a severe complication of chronic kidney disease (CKD). Accumulation of urea and other toxic compounds leads to oxidative stress, inflammation and destruction of the blood-brain barrier. Carbon monoxide (CO) and hydrogen sulfide (H 2 S) have been shown to have anti-inflammatory, anti-apoptotic, and anti-proliferative properties. The aims of the present study were evaluated the protective effects of CO-releasing molecule (CORM3) and H 2 S donor (NaHS) on oxidative stress and neuronal death induced by CKD in the hippocampus and prefrontal cortex by considering interaction between CO and H 2 S on CBS expression. CORM3 or NaHS significantly compensated deficits in the antioxidant defense mechanisms, suppressed lipid peroxidation and reduced neuronal death in hippocampus and prefrontal cortex and improvement the markers of renal injury that induced by CKD. In addition, CORM3 or NaHS significantly improved CBS expression which were reduced by CKD. However, improving effects of CORM3 on antioxidant defense mechanisms, lipid peroxidation, neuronal death, renal injury and CBS expression were prevented by amino-oxy acetic acid (AOAA) (CBS inhibitor) and reciprocally improving effects of NaHS on all above indices were prevented by zinc protoporphyrin IX (Znpp) (HO-1 inhibitor). In conclusion, this study demonstrated that formation of CO and H 2 S were interdependently improved CKD-induced oxidative stress and neuronal death, which is may be through increased expression of CBS.