Manganese abated indomethacin-induced gastrohepatorenal toxicities in Rats via suppression of oxidative stress, polyamine catabolism, inflammation and activation of Caspase-3

Abstract

Indomethacin (IND) is a non-steroidal anti-inflammatory drug with many therapeutic benefits and multi-organ toxicities. Manganese (Mn) is a trace metal essential in many biological processes. However, there is dearth of information concerning the effect of Mn on IND-induced gastrohepatorenal damage in rats. This study investigated the mitigating effect of manganese on IND-induced gastrohepatorenal damage in rats. Adult male rats were assigned into four groups of eight rats each and were treated once daily for 14 days. Group 1 served as control; group 2 received IND alone (5 mg/kg); group 3 received IND (5 mg/kg) and Mn alone (10 mg/kg) and group 4 received Mn alone Mn alone (10 mg/kg). Administration of IND significantly increased ulcer score, ulcer index, titrable acidity and peptic activity and decreased pH, mucus content, hexosamine and sialic acid levels. IND also increased hepatorenal markers, myeloperoxidase (MPO), nitric oxide (•NO), malondialdehyde (MDA), lipid hydroperoxide (LOOH), protein carbonyl (PCO), spermine oxidase (SpmOX), putrescine Oxidase (PutOX), tumor necrosis factor-α (TNF-α) interleukin-1β (IL-1β), caspase-3 and decreased the activities of superoxide dismutase (SOD), catalase, glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione (GSH) level relative to control. Co-administration of IND and Mn significantly decreased ulcerogenic parameters, hepatorenal markers, MPO, •NO, MDA, LOOH, PCO, SpmOX, PutOX, TNF-α, IL-1β, caspase-3 and increased antioxidant status relative to IND alone group.Histological examination showed that injuries induced by IND were ameliorated by Mn rats.Mn suppressed IND-induced oxidative stress, inflammation, polyamine catabolism and caspase-3 activation in the liver and kidney of the rats.