Amelioration of intestinal ischemia reperfusion injury by carvedilol via regulation of eNOS/VEGF-A and inflammasome/ IL1β/ TNFα pathways

Abstract

Intestinal ischemia reperfusion (IIR) is a life threating clinical disorder and a serious emergency case with high mortality rate. Finding ameliorative agents is a critical requisite to safeguard the tissue against its harmful effect not only on the intestine, but also on other organs especially the heart. Therefore, we tried in the current study to evaluate the role of carvedilol (CAR); an effective beta and alpha blocker with anti-oxidant, anti-apoptotic, anti-inflammatory properties and a metabolic regulator, on both cardiac and intestinal tissue in a model of IIR. Rats were randomly allocated into 4 groups: Sham group, IIR group and CAR treated groups with IIR in 2 different doses; CAR treated group in low dose (CLD) (10 mg/kg), CAR treated group in high dose (CHD) (20 mg/kg). Interestingly, CAR significantly decreased the elevated levels of cardiac enzymes, tissue malondialdehyde (MDA), inflammasome, interleukin 1β (IL1β), tumor necrosis factor alpha (TNFα) and caspase3. However, CAR co-administration normalized the tissue level of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), antioxidant parameters; reduced glutathione (GSH), total antioxidant capacity (TAC) with obvious improvement of the histopathological changes. CAR could ameliorate IIR induced damage in a dose dependent manner via its anti-oxidant and anti-inflammatory properties with regulation of eNOS/VEGF-A and inflammasome/IL1β/TNFα pathways and it can be considered as a potential therapeutic agent against such injury.

Keywords: Carvedilol; Interleukin 1β; Intestinal ischemia reperfusion; Vascular endothelial growth factor.