General Physiology and Biophysics Revised manuscript #1 Title: Gastroprotective effect of ghrelin against indomethacin-induced gastric injury in rats; possible role of heme oxygenase -1 pathway. Running title: effect of ghrelin against gastric injury
نویسندگان
چکیده
Abstract Ghrelin has been shown to ameliorate gastric injury by several mechanisms in experimental animal models. The present study aimed to investigate the effect of pretreatment with ghrelin on indomethacin induced gastric injury in rats and the role of heme oxygenase -1(HO-1) pathway as a novel mechanism underlying the gastroprotective effect of ghrelin. In all groups studied, ulcer score (U.S), ulcer index (U.I) and preventive index (P.I) were evaluated and the gastric inflammatory biomarkers including levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and myeloperoxidase (MPO) activity as well as prostaglandin E2(PGE2) , malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), heme oxygenase-1 (HO-1) and bilirubin as an indicator of HO activity were measured. Indomethacin induced significant elevation in U.S and U.I as well as the inflammatory and the oxidative markers and reduced the PGE2 in addition to HO-1 level and activity. Pretreatment with ghrelin reversed these results. In order to elucidate the possible role of HO-1 in mediating the protective effects of ghrelin, tin protoporphyrin (SnPP) HO-1 blocker was administrated, it significantly attenuated the gastroprotective effect of ghrelin. In conclusion HO-1 activity significantly contributes toward ghrelinmediated gastroprotection.
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