Involvement of alcohol and aldehyde dehydrogenase activities on hepatic retinoid metabolism and its possible participation in the progression of rat liver regeneration.
Liver alcohol dehydrogenase (ADH) activity is decreased towards exogenous substrates after partial hepatectomy (PH), probably due to putative endogenous substrates acting as ADH inhibitors. Hence, retinoids could be suitable candidates as such endogenous substrates. Therefore, cytosolic ADH kinetic analysis using several substrates, liver cytosolic and mitochondrial aldehyde dehydrogenase (ALDH) activities, retinal and retinol content, as well as expression of proteins for ADH and CRBPI (a retinol carrier protein) were determined in liver samples, at two stages of liver regeneration (one- or two-thirds PH). The effect of inhibiting in vivo liver ADH by 4-methylpyrazole (4-MP) was also evaluated after 70%-PH. With 70%-PH, in vitro ADH activity towards exogenous alcohols and aldehydes was diminished, but retinol oxidation was increased and retinal reduction was decreased. These activities that be due to the participation of an ADH type which did not correlate with the amount of immunoreactive ADH protein. Cytosolic and mitochondrial ALDH activities oxidized actively retinal, whereas retinol and CBRP-I expression were reduced in these animals. With 30%-PH, these changes were less evident and sometimes opposite to those found with 70%-PH. In addition, retinol readily inhibited ADH-mediated ethanol oxidation. Interestingly, in vivo 4-MP administration inhibited ADH activity in a dose-dependent manner correlating with a progressive inhibition of liver regeneration. In conclusion, PH-induced inhibition of ADH (mainly type I) seems to be related to ADH-mediated retinoid metabolism during liver proliferation. Thus, results suggest a role of ADH in retinoid metabolism, which is apparently required during rat liver regeneration.
López-Valencia
Verónica
V
Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), México 04510, D.F., Mexico.
Rangel
Pablo
P
Rodríguez
Sandra
S
Hernández-Muñoz
Rolando
R
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D000077604:Fomepizole; D006498:Hepatectomy / Q000379:methods; D007700:Kinetics; D008099:Liver / Q000378:metabolism* / Q000502:physiology / Q000601:surgery; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D024101:Mitochondrial Proteins / Q000187:drug effects / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012172:Retinaldehyde / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism*; D013347:Subcellular Fractions; D013937:Thymidine Kinase / Q000378:metabolism; D013997:Time Factors; D014801:Vitamin A / Q000378:metabolism
D024101:Mitochondrial Proteins; D011720:Pyrazoles; D012176:Retinoids; D014801:Vitamin A; D000431:Ethanol; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D013937:Thymidine Kinase; D012172:Retinaldehyde