Gastroprotective effect of heme-oxygenase 1/biliverdin/CO pathway in  ethanol-induced gastric damage in mice.
Our objective was to evaluate the role of heme-oxygenase 1 (HO-1)/biliverdin/CO pathway in gastric defense against ethanol-induced gastric damage in mice. Mice were pre-treated with saline, hemin (HO-1 inducer), biliverdin (HO-1 product), dimanganese decacarbonyl (DMDC, CO donor) or zinc protoporphyrin IX (ZnPP IX, HO-1 antagonist). Another group received soluble guanylate cyclase (sGC) inhibitor (ODQ) 30 min before hemin, biliverdin or DMDC. After 30 min, gastric damage was induced by ethanol. After one hour, rats were sacrificed. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malonylaldehyde (MDA), glutathione (GSH) or bilirubin. HO-1 expression was determined after saline or ethanol administration by polymerase chain reaction (PCR) or immunohistochemistry. Ethanol (25% or 50%) induced gastric damage, increased MDA levels and reduced GSH in the gastric tissue. Ethanol 50% increased HO-1 mRNA transcripts, HO-1 immunoreactivity, and bilirubin concentration in gastric mucosa. Pre-treatment with hemin reduced gastric damage and MDA formation and increased GSH concentration in the gastric mucosa. ZnPP IX amplified the ethanol-induced gastric lesion, increased MDA formation and decreased GSH concentration in gastric mucosa. Biliverdin and DMDC reduced gastric damage and MDA formation and increased GSH concentration in the gastric tissue. ODQ completely abolished the DMDC protective gastric effect. However, effects of hemin or biliverdin did not change with ODQ treatment. Our results suggest that HO-1/biliverdin/CO pathway plays a protective role against ethanol-induced gastric damage through mechanisms that can be dependent (CO) or independent (biliverdin) of sGC activation.
Gomes
Antoniella S
AS
Brazilian Semi-Arid Institute of Biomedicine (INCT-IBISAB), School of Medicine, Federal University of Ceará, Rua Cel. Nunes de Melo, 1315, CEP: 60430-270, Fortaleza- CE, Brazil.
Gadelha
Gemima G
GG
Lima
Samara J
SJ
Garcia
Joyce A
JA
Medeiros
Jand Venes R
JV
Havt
Alexandre
A
Lima
Aldo A
AA
Ribeiro
Ronaldo A
RA
Brito
Gerly Anne C
GA
Cunha
Fernando Q
FQ
Souza
Marcellus H L P
MH
D000818:Animals; D001663:Bilirubin / Q000494:pharmacology; D001664:Biliverdine / Q000378:metabolism*; D002248:Carbon Monoxide / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D011524:Protoporphyrins / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology
D011524:Protoporphyrins; C017803:zinc protoporphyrin; D000431:Ethanol; D008315:Malondialdehyde; D006427:Hemin; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; D005978:Glutathione; D001664:Biliverdine; D001663:Bilirubin