Combined melatonin and curcumin treatment ameliorates renal ischemia–reperfusion injury via reducing oxidative stress, inflammation, and apoptosis in rats

Renal ischemia-reperfusion (Isc-Rep) injury commonly occurs during kidney transplantation, renal vascular surgery, or traumatic hemorrhagic shock, and is marked by excessive oxidative stress and inflammation. We aimed to examine the antioxidant properties of the melatonin-curcumin combination in an experimental renal Isc-Rep model in rats. Thirty-five rats were allocated into five distinct experimental groups. While the rats in the Control (C) group did not undergo any surgical procedure, each of the rats in the remaining groups underwent 45 minutes of renal ischemia followed by 2 h of reperfusion. In all experimental groups, except the Isc-Rep group, the rats were administered an active compound immediately prior to reperfusion, namely melatonin (MEL, 20 mg/kg), curcumin (CUR, 200 mg/kg), or a combination of MEL-CUR. In all groups, histological evaluation was carried out, while apoptotic cell analyses were similarly performed by means of the TUNEL method. In addition, oxidative stress parameters (TOS, TAS, OSI), inflammatory cytokines (TNF-α, IL-6, and IL-1β), superoxide-dismutase (SOD), and malondialdehyde (MDA) activity levels were also examined. Histological evaluation demonstrated that renal Isc-Rep-induced cellular damage, tubular dilatation, and inflammation were significantly reduced in the MEL-CUR groups in comparison with the Isc-Rep group (p < 0.005). Furthermore, statistically significant differences were observed among the groups in TOS, TAS, OSI, TNF-α, IL-6, and IL-1β levels (p < 0.005). The co-administration of melatonin and curcumin resulted in greater protection against ischemia-reperfusion-induced renal damage compared with either treatment alone. Moreover, the co-administration of these antioxidant agents demonstrates greater therapeutic efficacy compared to their individua.