IADR Abstract Archives
Expression of Xenobiotic Metabolising Enzymes in Oral Mucosa and Tissue-Engineered Oral Mucosa Equivalents
Objectives: Xenobiotic compounds are external foreign molecules that interact with our tissues and cells. These foreign molecules need to be removed in order to maintain a healthy status and certain organs of the body, such as the liver and skin, contain metabolising enzymes that are able to deactivate xenobiotic compounds by converting them into usually less toxic molecules called metabolites. There is a movement within the pharmaceutical industry to deliver drugs via the oral mucosa. However, the abundance and location of xenobiotic metabolizing enzymes in the oral mucosa is unknown. Here we characterised, for the first time, the expression of a sub-set of metabolising enzymes in native, skin and oral mucosa, and compared these to tissue-engineered oral mucosal (TEOM) equivalents to elucidate enzymatic profiles.
Methods: Immunohistochemistry using antibodies directed against cytochrome P450 enzymes CYP2E1, CYP3A4, CYP3A43, CYP3A5, flavin-containing monooxygenase (FMO) 4 and 5, glutathione S-transferase (GST)–Pi, aldehyde dehydrogenase (ALDH2), N-acetyltransferase 1 (NAT1) and UDP-glucuronosyltransferase (UGT1A6) was performed on wax-embedded sections of native, normal oral mucosa (NOM), skin and TEOM to determine protein expression and localisation within tissue sections.
Results: Immunohistochemical results revealed that the location of xenobiotic enzyme expression varies between human skin and NOM. Expression of GST-Pi, FMO4, FMO5, NAT-1, ALDH2, CYP3A4 was similar in all tissues with immune-reactivity throughout the epithelium. CYP2E1 expression was mainly restricted to the basal epithelium as was expression for CYP3A5 and UGT1A6 although expression of this enzyme was absent in TEOM. Expression of FMO3 was throughout the normal epithelium, restricted to basal cells in skin and was weak in the TEOM.
Conclusions: We identified variations in enzyme expression between human skin, NOM and TEOM. This data will be useful when investigating xenobiotic metabolism of topically delivered compounds.
Methods: Immunohistochemistry using antibodies directed against cytochrome P450 enzymes CYP2E1, CYP3A4, CYP3A43, CYP3A5, flavin-containing monooxygenase (FMO) 4 and 5, glutathione S-transferase (GST)–Pi, aldehyde dehydrogenase (ALDH2), N-acetyltransferase 1 (NAT1) and UDP-glucuronosyltransferase (UGT1A6) was performed on wax-embedded sections of native, normal oral mucosa (NOM), skin and TEOM to determine protein expression and localisation within tissue sections.
Results: Immunohistochemical results revealed that the location of xenobiotic enzyme expression varies between human skin and NOM. Expression of GST-Pi, FMO4, FMO5, NAT-1, ALDH2, CYP3A4 was similar in all tissues with immune-reactivity throughout the epithelium. CYP2E1 expression was mainly restricted to the basal epithelium as was expression for CYP3A5 and UGT1A6 although expression of this enzyme was absent in TEOM. Expression of FMO3 was throughout the normal epithelium, restricted to basal cells in skin and was weak in the TEOM.
Conclusions: We identified variations in enzyme expression between human skin, NOM and TEOM. This data will be useful when investigating xenobiotic metabolism of topically delivered compounds.