Immunohistochemical localization of the antioxidant enzymes biliverdin reductase and heme oxygenase-2 in human and pig gastric fundus

The intrinsic antioxidant capacities of the bile pigments biliverdin and bilirubin are increasingly recognized since both heme degradation products can exert beneficial cytoprotective effects due to their scavenging of oxygen free radicals and interaction with antioxidant vitamins. Several studies have been published on the localization of the carbon monoxide producing enzyme heme oxygenase-2 (HO-2), which concomitantly generates biliverdin; histochemical data on the distribution of biliverdin reductase (BVR), converting biliverdin to bilirubin, are still very scarce in large mammals including humans. The present study revealed by means of immunohistochemistry the presence of BVR and HO-2 in mucosal epithelial cells and in the endothelium of intramural vessels of both human and porcine gastric fundus. In addition, co-labeling with the specific neural marker protein-gene product 9.5 (PGP 9.5) demonstrated that both BVR and HO-2 were present in all intrinsic nerve cell bodies of both submucous and myenteric plexuses, while double labeling with c-Kit antibody confirmed their presence in intramuscular interstitial cells of Cajal (ICC). Our results substantiate the hypothesis that BVR, through the production of the potent antioxidant bilirubin, might be an essential component of normal physiologic gastrointestinal defense in man and pig.