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-α (TNF-α), interleukin-1β (IL-1β) and
myeloperoxidase (MPO) activity as well as prostaglandin E2 (PGE2), malondialdehyde (MDA),
glutathione (GSH), superoxide dismutase (SOD), HO-1 and bilirubin as an indicator of heme oxygenase
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 ghrelin-mediated gastroprotection. |
