The effect of induction of endogenous CO by heme-oxygenase inducer, hemin versus heme-oxygenase blocker, zinc mesoporphyrin on gastric secretion and ulceration under different conditions in adult male albino rats.

Abstract

Although its role and importance is less well studied, carbon monoxide (CO) has been identified as the second gasotransmitter in the GI tract. This study was performed to investigate the effect of modifying the endogenous CO production by altering heme oxygenase (HO) activity either by induction through hemin administration or inhibition by zinc mesoporphyrin administration on gastric secretion and ulceration induced by either cold restraint stress (CRS) or indomethacin (IND) treatment in adult male albino rats. Our results revealed that hemin significantly increased HO-1 levels with an increase in carboxyhemoglobin (COHb) level while zinc mesoporphyrin significantly decreased HO-1 levels with a decrease in COHb level in all groups. Hemin pretreatment significantly attenuated the gastric mucosal lesions induced by CRS and IND administration, which was accompanied by significant reduction in free and total acidity of gastric secretion, decreased proteolytic activity and marked attenuation of lipid peroxidation inspite of decreased NO and PGE2 levels. On the other hand, Inhibition of HO-1 activity by zinc mesoporphyrin prevented most of the effects caused by hemin administration except for its similar reduction in gastric mucosal NO and PGE2 levels. On conclusion, Hemin exerts a protective effect against CRS and IND-induced gastric ulcers possibly via inducing HO-1 and increasing endogenous production of CO (Tab. 2, Fig. 4, Ref. 75).