Xenobiotic-metabolizing enzymes in pig nasal and hepatic tissues

Abstract

1. A study of xenobiotic-metabolizing enzyme activity of the olfactory and respiratory epithelium in the pig was undertaken. The results indicated that porcine olfactory mucosa contains all the components of the P450 system. 2. Monooxygenase activities were much higher in olfactory than in respiratory microsomes, and the olfactory activities dependent on CYP2A were higher than those in the liver. By contrast, the olfactory monooxygenases associated with CYP2E1 were poorly or not detected, whereas CYP2G1 and a protein immunorelated to CYP1A2 were expressed in the olfactory epithelium. 3. The activities of several non oxidative enzymes (glutathione S-transferase, UDP-glucuronyl transferase, epoxide hydrolase, DT-diaphorase, benzaldehyde and propionaldehyde dehydrogenases, and various esterases) were also determined in porcine tissues and were found to be higher in the olfactory than in the respiratory mucosa, but lower or similar to those in liver. 4. An unexpected finding was a higher activity of olfactory UDP-GT compared with that of liver when 1-naphtol but not p-hydroxybiphenyl (a good substrate for a specific olfactory UDP-GT(olf) in bovine and rat) was used as substrate, suggesting a porcine specific expression of UDP-GT isoforms. 5. The results taken together indicate that the olfactory epithelium of mammals has a similar cytochrome P450 profile with the CYP2A and CYP2G1 as dominant isoforms, whereas the olfactory non-oxidative enzymes appear qualitatively and quantitatively expressed to different extents.

Expression and inducibility of CYP1A1, 1A2, 1B1 by β-naphthoflavone and CYP2B22, 3A22, 3A29, 3A46 by rifampicin in the respiratory and olfactory mucosa of pig

“…The expression of CYP2B and 3A genes in these nasal tissues was not affected also by the ␤NF pig treatment. The resistance of CYP2B to induction in the porcine nasal tissues is in keeping with some previous reports on rodents (Ling et al, 2004;Minn et al, 2005) and may reflect the relative abundance of this isoform among the nasal CYP enzymes of both rodents (Ling et al, 2004) and pigs (Marini et al, 1998). It appears that the regulation mechanism of CYP3As and CYP2Bs in the nasal mucosa involves tissue-enriched transcriptional factors other than PXR, CAR and HNF4␣, whose expression levels are fundamental for these CYPs in liver (Wortham et al, 2007).…”

“…A recent study revealed that olfactory tissue of rat expresses a substantial level of CYP3A9 but not CYP3A1 and 3A2 (Minn et al, 2005). Also in the olfactory microsomes of pig, a CYP3A protein band was immunodetected by anti-rat CYP3A1 but the identity of this protein has not been established (Marini et al, 1998).…”

Nasal Passages of Göttingen Minipigs from the Neonatal Period to Young Adult

“…Studies on nasal tissues have been even rarer, and the histologic examination in these few cases was limited to a few samples of the mucosa (Marini et al 1998;Rankløve et al 2006). Careful mapping of induced nasal lesions in frequently used animal species such as mice, rats, dogs, and monkeys has been very helpful to establish the mode of action and facilitate extrapolation of the findings to humans (Young 1981;Woutersen et al 1987;Boorman, Morgan, and Uriah 1990;Morgan and Monticello 1990;Harkema 1991;Mery et al 1994;Herbert and Leininger 1999;Harkema, Carey, and Wagner 2006;Carey et al 2007;Craven et al 2007).…”

The effects of subcutaneous administration of T-2 toxin on liver drug metabolizing enzymes in piglets

“…In humans, as has been indicated by findings that the CYP3A4 comprises 30% of total P-450 and metabolizes 36% of all drugs [18]. Pig liver microsomes have been found to possess the erythromycin-, ethylmorphine-and triacethloleandomycin N-demethylase, nifedipine oxidase and testosterone 6-hydroxylase [5,20,27]. In this study, the O-debenzylase activity was determined by using DBF as a substrate.…”