Interspecies comparison of the glucuronidation processes in the man, monkey, pig, dog and rat.
OBJECTIVE
The study of interspecies differences in glucuronidation processes in the man, monkey, pig, dog and rat using liver microsomal fraction. The study is focused on determination of the enzyme activity of UGT1A6 (having also a toxicological importance) in microsomes of different species.


METHODS
For determination of glucuronides formed, an HPLC method with UV detection and LC-MS characterization was used. p-Nitrophenol and 4-methylumbelliferon and silybin were chosen as model substrates.


RESULTS
The data presented in this paper show an overall similarity in kinetic parameters of the UGT1A6 with p-nitrophenol and 4-methylumbelliferon for man, pig and monkey. The pattern of silybin glucuronides formed in monkey and dog samples are relatively close to this of the man.


CONCLUSIONS
For studies of glucuronidation of xenobiotics where the role UGT1A6 is expected, the use of pig and monkey microsomes should be considered. As an optimal model for study of silybin glucuronidation, both the rhesus monkey and dog (Beagle) seem to be the best models. To elucidate the role of the UGT forms involved in metabolism of silybin, the experiments with recombinant UGT enzymes are needed.
Matal
Jaroslav
J
Department of Pharmacology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
Jancova
Petra
P
Siller
Michal
M
Masek
Vlastimil
V
Anzenbacherova
Eva
E
Anzenbacher
Pavel
P
D000818:Animals; D004285:Dogs; D020719:Glucuronides / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism; D000882:Haplorhini; D006801:Humans; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology; D020011:Protective Agents / Q000378:metabolism; D051381:Rats; D000077385:Silybin; D012838:Silymarin / Q000378:metabolism; D013045:Species Specificity; D013552:Swine
D020719:Glucuronides; D020011:Protective Agents; D012838:Silymarin; D000077385:Silybin; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase