Cross-talk between carbon monoxide and hydrogen sulfide on the CBS expression and neurotoxicity induced by Chronic Kidney Disease in the male rats

Abstract

Abstract 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 (H2S) have been shown to have anti-inflammatory, anti-apoptotic, and anti-proliferative properties. The present study aimed to evaluate the protective effects of CO-releasing molecule (CORM3) and H2S donor (NaHS) on oxidative stress and neuronal death induced by CKD in the hippocampus and prefrontal cortex by considering theinteraction between CO and H2S on CBS expression. CORM3 or NaHS significantly compensated deficits in the antioxidant defense mechanisms, suppressed lipid peroxidationand reduced neuronal death in the hippocampus and prefrontal cortex and, improved the markers of renal injury induced by CKD. In addition, CORM3 or NaHS significantly improved CBS expression which wasreduced by CKD. However, improving effects of CORM3 on antioxidant defense mechanisms, lipid peroxidation, neuronal death, renal injury, and CBS expression was 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 the formation of CO and H2S interdependently improved CKD-induced oxidative stress and neuronal death, which may bethrough increased expression of CBS.