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dc.contributor.authorPappas, P.en
dc.contributor.authorStephanou, P.en
dc.contributor.authorVasiliou, V.en
dc.contributor.authorMarselos, M.en
dc.rightsDefault Licence-
dc.subjectAldehyde Dehydrogenase/metabolismen
dc.subjectCytochrome P-450 CYP1A1/metabolismen
dc.subjectCytochrome P-450 CYP1A2/metabolismen
dc.subjectCytochrome P-450 CYP2B1/metabolismen
dc.subjectEnzyme Induction/drug effectsen
dc.subjectLiver/drug effects/enzymologyen
dc.subjectMuscle Relaxants, Central/adverse effects/*pharmacologyen
dc.subjectParalysis/chemically induced/*enzymologyen
dc.subjectRats, Wistaren
dc.subjectRetinal Dehydrogenaseen
dc.subjectSpecies Specificityen
dc.subjectTime Factorsen
dc.subjectZoxazolamine/adverse effects/*pharmacologyen
dc.titleZoxazolamine-induced paralysis in two rat substrains: differences in hepatic drug metabolismen
heal.type.enJournal articleen
heal.type.elΆρθρο Περιοδικούel
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.abstractAldehyde dehydrogenase (ALDH) is involved in the metabolism of endogenous and exogenous aldehydes originating from biogenic amines, lipids, food and drugs. Rat liver contains at least two cytosolic ALDHs that can be stimulated by inducers of drug metabolism. Phenobarbital- type inducers increase ALDH1 activity while polycyclic aromatic hydrocarbons (such as benzo[alpha]pyrene) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increase ALDH3c isoenzyme activity. Two rat substrains were isolated according to a different induction of hepatic ALDH after treatment with phenobarbital (PB). Animals that responded to treatment (RR) and those that did not respond (rr) were inbred and divided into two homogenous groups. These animals constituted an ideal experimental model due to their common origin. Apart from the dramatic induction of cytosolic ALDH1 and ALDH3c, the effects of PB on pentoxy-, ethoxy- and methoxy-resorufin-O-dealkylase (P-, E-, and MROD) between the two substrains were also studied. 3-Methylcholanthrene (3MC) greatly increased ALDH3c levels in both substrains, although it was slightly more pronounced in the rr rats, in which it was assessed either as ALDH3c or as total cytosolic ALDH. A similar trend was also noted in EROD, PROD and MROD activities. Dealkylation of the methoxy group was found to be statistically different between the two substrains (rr > RR). The relevance of the biochemical findings with the in vivo hepatic capacity for drug metabolism was investigated by measuring the duration of zoxazolamine paralysis. Both animal substrains were tested with zoxazolamine either without pretreatment or after administration of PB or 3MC: the paralysis produced by zoxazolamine lasted for a longer period in rr than in RR rats. After pretreatment with PB, the duration of paralysis was greatly reduced, but the differences between the two substrains remained. Pretreatment with various doses of 3MC produced differences in the duration of paralysis in RR and rr rats, although the time period was much shorter than that observed in control animals.en
heal.journalNameEur J Drug Metab Pharmacokineten
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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