Species variations in cutaneous alcohol dehydrogenases and aldehyde dehydrogenases may impact on toxicological assessments of alcohols and aldehydes.
Alcohol dehydrogenase (ADH; EC. 1.1.1.1) and aldehyde dehydrogenase (ALDH; EC 1.2.1.3) play important roles in the metabolism of both endogenous and exogenous alcohols and aldehydes. The expression and localisation patterns of ADH (1-3) and ALDH (1-3) were investigated in the skin and liver of the mouse (BALB/c and CBA/ca), rat (F344) and guinea-pig (Dunkin-Hartley), using Western blot analysis and immunohistochemistry with class-specific antisera. ALDH2 expression and localisation was also determined in human skin, while ethanol oxidation, catalysed by ADH, was investigated in the mouse, guinea-pig and human skin cytosol. Western blot analysis revealed that ADH1, ADH3, ALDH1 and ALDH2 were expressed, constitutively, in the skin and liver of the mouse, rat and guinea-pig. ADH2 was not detected in the skin of any rodent species/strain, but was present in all rodent livers. ALDH3 was expressed, constitutively, in the skin of both strains of mouse and rat, but was not detected in guinea-pig skin and was absent in all livers. Immunohistochemistry showed similar patterns of expression for ADH and ALDH in both strains of mouse, rat, guinea-pig and human skin sections, with localisation predominantly in the epidermis, sebaceous glands and hair follicles. ADH activity (apparent V(max), nmoles/mg protein/min) was higher in liver (6.02-16.67) compared to skin (0.32-1.21) and lower in human skin (0.32-0.41) compared to mouse skin (1.07-1.21). The ADH inhibitor 4-methyl pyrazole (4-MP) reduced ethanol oxidation in the skin and liver in a concentration dependent manner: activity was reduced to approximately 30-40% and approximately 2-10% of the control activity, in the skin and liver, respectively, using 1 mM 4-MP. The class-specific expression of ADH and ALDH enzymes, in the skin and liver and their variation between species, may have toxicological significance, with respect to the metabolism of endogenous and xenobiotic alcohols and aldehydes.
Cheung
Connie
C
Department of Molecular Toxicology, Section of Biological Chemistry, Division of Biomedical Sciences, Sir Alexander Fleming Building, Imperial College School of Medicine, South Kensington, London, UK.
Davies
Non G
NG
Hoog
Jan-Olov
JO
Hotchkiss
Sharon A M
SA
Smith Pease
Camilla K
CK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000438:Alcohols / Q000633:toxicity*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D003720:Densitometry; D005260:Female; D000077604:Fomepizole; D006168:Guinea Pigs; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007223:Infant; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008875:Middle Aged; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000187:drug effects / Q000201:enzymology*; D013045:Species Specificity; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology
D000438:Alcohols; D000447:Aldehydes; D000931:Antidotes; D011720:Pyrazoles; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase