Biotransformation of Dimetridazole by Primary Cultures of Pig Hepatocytes
Monolayer cultures of pig hepatocytes were used to investigate the role of the liver in the biotransformation of the veterinary drug dimetridazole (1,2-dimethyl-5-nitroimidazole). 14C-Labeled dimetridazole (DMZ) was primarily hydroxylated to 1-methyl-2-hydroxymethyl-5-nitroimidazole (up to 90%) and...
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Published in | Journal of agricultural and food chemistry Vol. 45; no. 10; pp. 3985 - 3990 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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American Chemical Society
01.10.1997
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Abstract | Monolayer cultures of pig hepatocytes were used to investigate the role of the liver in the biotransformation of the veterinary drug dimetridazole (1,2-dimethyl-5-nitroimidazole). 14C-Labeled dimetridazole (DMZ) was primarily hydroxylated to 1-methyl-2-hydroxymethyl-5-nitroimidazole (up to 90%) and to a minor extent N-demethylated to 2-methyl-(4,5)-nitroimidazole (6−10%). Prolonged incubation with the parent drug but also the 2-hydroxymethyl metabolite resulted in the formation of two other minor metabolites. The major one of these was identified as the glucuronide of the 2-hydroxymethyl metabolite, based on its molecular mass and the succesful hydrolysis with β-glucuronidase. The second showed a molecular mass of 144 and is hypothesized to be 2-hydroxymethyl-5-nitroimidazole. No evidence was obtained for the formation of a cysteine or glutathione conjugate involved in the detoxification of reactive intermediates. In addition to free metabolites, there was a time-related formation of protein-bound metabolites up to a maximum of 30 pmol/mg of protein after exposure to 50 μM DMZ for 48 h. In general, these metabolites accounted for 0.06−0.15% of the metabolized DMZ. Unextractable metabolites were also observed after incubation of cells with the 2-hydroxymethyl and 1-desmethyl metabolites. It is concluded that the 1-desmethyl and, in particular, the 2-hydroxymethyl metabolite are the major metabolites formed by pig hepatocytes. These compounds are thus far the only metabolites identified in vivo, but together with the parent compound, they accounted for only a small part (<5%) of the excreted drug. Therefore, the site of formation of the majority of the unknown in vivo metabolites may be extrahepatic, and complimentary models are needed to investigate this hypothesis. Keywords: Pig hepatocytes; dimetridazole; nitroimidazoles; bound residues |
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AbstractList | Monolayer cultures of pig hepatocytes were used to investigate the role of the liver in the biotransformation of the veterinary drug dimetridazole (1,2-dimethyl-5-nitroimidazole). 14C-Labeled dimetridazole (DMZ) was primarily hydroxylated to 1-methyl-2-hydroxymethyl-5-nitroimidazole (up to 90%) and to a minor extent N-demethylated to 2-methyl-(4,5)-nitroimidazole (6−10%). Prolonged incubation with the parent drug but also the 2-hydroxymethyl metabolite resulted in the formation of two other minor metabolites. The major one of these was identified as the glucuronide of the 2-hydroxymethyl metabolite, based on its molecular mass and the succesful hydrolysis with β-glucuronidase. The second showed a molecular mass of 144 and is hypothesized to be 2-hydroxymethyl-5-nitroimidazole. No evidence was obtained for the formation of a cysteine or glutathione conjugate involved in the detoxification of reactive intermediates. In addition to free metabolites, there was a time-related formation of protein-bound metabolites up to a maximum of 30 pmol/mg of protein after exposure to 50 μM DMZ for 48 h. In general, these metabolites accounted for 0.06−0.15% of the metabolized DMZ. Unextractable metabolites were also observed after incubation of cells with the 2-hydroxymethyl and 1-desmethyl metabolites. It is concluded that the 1-desmethyl and, in particular, the 2-hydroxymethyl metabolite are the major metabolites formed by pig hepatocytes. These compounds are thus far the only metabolites identified in vivo, but together with the parent compound, they accounted for only a small part (<5%) of the excreted drug. Therefore, the site of formation of the majority of the unknown in vivo metabolites may be extrahepatic, and complimentary models are needed to investigate this hypothesis. Keywords: Pig hepatocytes; dimetridazole; nitroimidazoles; bound residues Monolayer cultures of pig hepatocytes were used to investigate the role of the liver in the biotransformation of the veterinary drug dimetridazole (1,2-dimethyl-5-nitroimidazole). 14C-Labeled dimetridazole (DMZ) was primarily hydroxylated to 1-methyl-2-hydroxymethyl-5-nitroimidazole (up to 90%) and to a minor extent N-demethylated to 2-methyl-(4,5)-nitroimidazole (6-10%). Prolonged incubation with the parent drug but also the 2-hydroxymethyl metabolite resulted in the formation of two other minor metabolites. The major one of these was identified as the glucuronide of the 2-hydroxymethyl metabolite, based on its molecular mass and the successful hydrolysis with beta-glucuronidase. The second showed a molecular mass of 144 and is hypothesized to be 2-hydroxymethyl-5-nitroimidazole. No evidence was obtained for the formation of a cysteine or glutathione conjugate involved in the detoxification of reactive intermediates. In addition to free metabolites, there was a time-related formation of protein-bound metabolites up to a maximum of 30 pmol/mg of protein after exposure to 50 micromolar DMZ for 48 h. In general, these metabolites accounted for 0.06-0.15% of the metabolized DMZ. Unextractable metabolites were also observed after incubation of cells with the 2-hydroxymethyl and 1-desmethyl metabolites. It is concluded that the 1-desmethyl and, in particular, the 2-hydroxymethyl metabolite are the major metabolites formed by pig hepatocytes. These compounds are thus far the only metabolites identified in vivo, but together with the parent compound, they accounted for only a small part (5%) of the excreted drug. Therefore, the site of formation of the majority of the unknown in vivo metabolites may be extrahepatic, and complimentary models are needed to investigate this hypothesis Monolayer cultures of pig hepatocytes were used to investigate the role of the liver in the biotransformation of the veterinary drug dimetridazole (1,2-dimethyl-5-nitroimidazole). 14C-Labeled dimetridazole (DMZ) was primarily hydroxylated to 1-methyl-2-hydroxymethyl-5-nitroimidazole (up to 90%) and to a minor extent N-demethylated to 2-methyl-(4,5)-nitroimidazole (6-10%). Prolonged incubation with the parent drug but also the 2-hydroxymethyl metabolite resulted in the formation of two other minor metabolites. The major one of these was identified as the glucuronide of the 2-hydroxymethyl metabolite, based on its molecular mass and the succesful hydrolysis with β-glucuronidase. The second showed a molecular mass of 144 and is hypothesized to be 2-hydroxymethyl-5-nitroimidazole. No evidence was obtained for the formation of a cysteine or glutathione conjugate involved in the detoxification of reactive intermediates. In addition to free metabolites, there was a time-related formation of protein-bound metabolites up to a maximum of 30 pmol/mg of protein after exposure to 50 μM DMZ for 48 h. In general, these metabolites accounted for 0.06-0.15% of the metabolized DMZ. Unextractable metabolites were also observed after incubation of cells with the 2-hydroxymethyl and 1-desmethyl metabolites. It is concluded that the 1-desmethyl and, in particular, the 2-hydroxymethyl metabolite are the major metabolites formed by pig hepatocytes. These compounds are thus far the only metabolites identified in vivo, but together with the parent compound, they accounted for only a small part (<5%) of the excreted drug. Therefore, the site of formation of the majority of the unknown in vivo metabolites may be extrahepatic, and complimentary models are needed to investigate this hypothesis. |
Author | Heskamp, Henry H Kuiper, Harry A Polman, Theo H. G van Rhijn, Johannes A Foster, Brian C Hoogenboom, Laurentius A. P |
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Keywords | Liver Veterinary medicine Metabolism In vitro Protein Bound form Pig Antiprotozoal agent Vertebrata Biological fixation Mammalia Hepatocyte Animal Dimetridazole Parasiticid Artiodactyla Antibacterial agent Ungulata |
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References | Alvaro R. F. (atypb1/atypb2) 1992; 82 Lu A. Y. H. (atypb27/atypb28) 1984; 12 Hoogenboom L. A. P. (atypb13/atypb14) 1989; 19 Vroomen L. H. M. (atypb39/atypb40) 1987; 64 Wolf F. J. (atypb49/atypb50) 1983; 31 West S. B. (atypb41/atypb42) 1982; 41 Hoogenboom L. A. P. (atypb21/atypb22) 1994; 24 Wislocki P. G. (atypb45/atypb46) 1984; 49 Anonymous (atypb3/atypb4) 1995; 137 Carignan G. (atypb7/atypb8) 1991; 8 Voogd C. E. (atypb37/atypb38) 1974; 26 Hoogenboom L. A. P. (atypb19/atypb20) atypb43/atypb44 Carignan G. (atypb5/atypb6) 1988; 71 Law G. L. (atypb25/atypb26) 1963; 196 Swaminathan S. (atypb35/atypb36) 1978 Hoogenboom L. A. P. (atypb15/atypb16) 1991; 29 Shaw I. C. (atypb33/atypb34) Cohen S. M. (atypb9/atypb10) 1973; 51 Wislocki P. G. (atypb47/atypb48) 1984; 49 Gottschall D. W. (atypb11/atypb12) 1995; 43 Peterson G. L (atypb31/atypb32) 1977; 83 Miwa G. T. (atypb29/atypb30) 1982; 41 Hoogenboom L. A. P. (atypb17/atypb18) 1992; 6 Law F. C. P. (atypb23/atypb24) 1996; 13 |
References_xml | – volume: 82 start-page: 30 year: 1992 ident: atypb1/atypb2 publication-title: Chem. Biol. Interact. doi: 10.1016/0009-2797(92)90011-9 contributor: fullname: Alvaro R. F. – volume: 12 start-page: 9 year: 1984 ident: atypb27/atypb28 publication-title: Biochem. Soc. Trans. doi: 10.1042/bst0120009 contributor: fullname: Lu A. Y. H. – volume: 49 start-page: 25 year: 1984 ident: atypb45/atypb46 publication-title: Chem.-Biol. Interact. contributor: fullname: Wislocki P. G. – volume: 26 start-page: 490 year: 1974 ident: atypb37/atypb38 publication-title: Mutat. Res. doi: 10.1016/S0027-5107(74)80049-7 contributor: fullname: Voogd C. E. – volume: 13 start-page: 209 year: 1996 ident: atypb23/atypb24 publication-title: Food Addit. Contam. contributor: fullname: Law F. C. P. – volume: 6 start-page: 237 year: 1992 ident: atypb17/atypb18 publication-title: Toxicol. In Vitro contributor: fullname: Hoogenboom L. A. P. – volume: 137 start-page: 230 year: 1995 ident: atypb3/atypb4 publication-title: Vet. Rec. doi: 10.1136/vr.137.10.230 contributor: fullname: Anonymous – volume: 8 start-page: 475 year: 1991 ident: atypb7/atypb8 publication-title: Food Addit. Contam. doi: 10.1080/02652039109373997 contributor: fullname: Carignan G. – volume: 64 start-page: 179 year: 1987 ident: atypb39/atypb40 publication-title: Chem.-Biol. Interact. contributor: fullname: Vroomen L. H. M. – volume: 41 start-page: 279 year: 1982 ident: atypb41/atypb42 publication-title: Chem.-Biol. Interact. contributor: fullname: West S. B. – volume: 196 start-page: 1225 year: 1963 ident: atypb25/atypb26 publication-title: Nature contributor: fullname: Law G. L. – volume: 41 start-page: 312 year: 1982 ident: atypb29/atypb30 publication-title: Chem. Biol. Interact. contributor: fullname: Miwa G. T. – start-page: 380 volume-title: Proceedings of the EuroResidue II conference; Haagsma, N., Ruiter, A., Czedik-Eysenberg, P. B., Eds.; University of Utrecht: 1993; ident: atypb19/atypb20 contributor: fullname: Hoogenboom L. A. P. – volume: 71 start-page: 1149 year: 1988 ident: atypb5/atypb6 publication-title: J. Assoc. Off. Anal. Chem. contributor: fullname: Carignan G. – start-page: 97 volume-title: Carcinogenesis, Vol 4, Nitrofurans year: 1978 ident: atypb35/atypb36 contributor: fullname: Swaminathan S. – volume: 24 start-page: 727 year: 1994 ident: atypb21/atypb22 publication-title: Xenobiotica contributor: fullname: Hoogenboom L. A. P. – volume: 29 start-page: 328 year: 1991 ident: atypb15/atypb16 publication-title: Food Chem. Toxicol. contributor: fullname: Hoogenboom L. A. P. – volume: 31 start-page: 564 year: 1983 ident: atypb49/atypb50 publication-title: J. Agric. Food Chem. doi: 10.1021/jf00117a024 contributor: fullname: Wolf F. J. – volume: 19 start-page: 1219 year: 1989 ident: atypb13/atypb14 publication-title: Xenobiotica contributor: fullname: Hoogenboom L. A. P. – volume: 43 start-page: 2525 year: 1995 ident: atypb11/atypb12 publication-title: J. Agric. Food Chem. contributor: fullname: Gottschall D. W. – volume: 83 start-page: 356 year: 1977 ident: atypb31/atypb32 publication-title: Anal. Biochem. doi: 10.1016/0003-2697(77)90043-4 contributor: fullname: Peterson G. L – volume: 51 start-page: 417 year: 1973 ident: atypb9/atypb10 publication-title: J. Natl. Cancer Inst. doi: 10.1093/jnci/51.4.1323 contributor: fullname: Cohen S. M. – ident: atypb43/atypb44 – volume: 49 start-page: 38 year: 1984 ident: atypb47/atypb48 publication-title: Chem.-Biol. Interact. contributor: fullname: Wislocki P. G. – start-page: 335 volume-title: Proceedings of the EuroResidue I conference; Haagsma, N., Ruiter, A., Czedik-Eysenberg, P. B., Eds.; University of Utrecht: 1990; ident: atypb33/atypb34 contributor: fullname: Shaw I. C. |
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SubjectTerms | Antibiotics. Antiinfectious agents. Antiparasitic agents Antiparasitic agents Biological and medical sciences CARNE CARNE DE CERDO DRUGS MEAT Medical sciences MEDICAMENT MEDICAMENTOS Pharmacology. Drug treatments PORK RESIDU RESIDUES RESIDUOS RIKILT VIANDE VIANDE PORCINE Wageningen Food Safety Research |
Title | Biotransformation of Dimetridazole by Primary Cultures of Pig Hepatocytes |
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