Crocin exerts improving effects on indomethacin-induced small intestinal ulcer by antioxidant, anti-inflammatory and anti-apoptotic mechanisms

Crocin is a plant-derived carotenoid and bears potent antioxidant property. Ranitidine (a histamine H۲ receptor blocker) is used for peptic ulcer treatment. The present study was planned to investigate the effects of crocin and ranitidine on indomethacin-induced ulcer in small intestine of rats. Animals were randomized into two major groups including indo-methacin (۱۰.۰۰ mg kg-۱, ulcer group, ۴۸ rats) and normal saline (۱.۰۰ mL kg-۱, intact group, ۴۸ rats) groups. Each of these two major groups was subdivided into eight subgroups for intra-peritoneal (IP) injections of normal saline, crocin (۲.۵۰, ۱۰.۰۰ and ۴۰.۰۰ mg kg-۱), ranitidine (۵.۰۰ and ۲۰.۰۰ mg kg-۱), crocin (۲.۵۰ and ۱۰.۰۰ mg kg-۱) plus ranitidine (۵.۰۰ mg kg-۱). Indomethacin induced intestinal ulcer was characterized by bleeding, inflammation, epithelial hyperplasia and crypt loss. This non-steroidal anti-inflammatory drug (NSAID), indomethacin decreased goblet cell number and superoxide dismutase (SOD) activity and increased small intestine weight, organo-somatic index (OSI), malodealdehyde (MDA), tumor necrosis factor-α (TNF-α) and caspase-۳ contents of intestine. Crocin resolved all the above-mentioned parameter changes induced by indomethacin. These treatments produced no significant effects on the above-mentioned parameters of intact group. The results of the present study showed tissue protective and anti-ulcer effects of crocin on small intestine by antioxidant, anti-inflammatory and anti-apoptotic mechanisms. Ranitidine alone showed no effect; however, in combination with crocin it exerted recovery effects. It is recommended that crocin, be considered as a therapeutic agent for NSAIDs-induced intestinal damage management.

Keywords:

Crocin , Indomethacin , Ranitidine , small intestinal ulcer