title: Comparative study of hydrolytic metabolism of dimethyl phthalate, dibutyl phthalate and di(2-ethylhexyl) phthalate by microsomes of various rat tissues.
abstract: Phthalates are used in food packaging, and are transferred to foods as contaminants. In this study, we examined the hydrolytic metabolism of dimethyl phthalate (DMP), dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) by rat tissue microsomes. We found that carboxylesterase and lipase contribute differently to these activities. When DMP, DBP and DEHP were incubated with rat liver microsomes, DBP was most effectively hydrolyzed to the phthalate monoester, followed by DMP, and the activity toward DEHP was marginal. In contrast, small-intestinal microsomes exhibited relatively higher activity toward long-side-chain phthalates. Pancreatic microsomes showed high activity toward DEHP and DBP. Liver microsomal hydrolase activity toward DMP was markedly inhibited by bis(4-nitrophenyl)phosphate, and could be extracted with Triton X-100. The activity toward DBP and DEHP was partly inhibited by carboxylesterase inhibitor, and was partly solubilized with Triton X-100. Ces1e, Ces1d and Ces1f expressed in COS cells exhibited the highest hydrolase activity toward DBP, showing a similar pattern to that of liver microsomes. Ces1e showed activity towards DMP and DEHP. Pancreatic lipase also hydrolyzed DBP and DEHP. Thus, carboxylesterase and lipase contribute differently to phthalate hydrolysis: short-side-chain phthalates are mainly hydrolyzed by carboxylesterase and long-side-chain phthalates are mainly hydrolyzed by lipase.
authors.affiliation: Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Ozaki
authors.affiliation: Faculty of Pharmaceutical Science, Hiroshima International University, Koshingai 5-1-1, Kure, Hiroshima, 737-0112, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Sugihara
authors.affiliation: Nihon Pharmaceutical University, Komuro 10281, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Nihon Pharmaceutical University, Komuro 10281, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Moriguchi
authors.affiliation: Nihon Pharmaceutical University, Komuro 10281, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Uramaru
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University, Nagaotoge-cho 45-1, Hirakata, Osaka 573-0101, Japan.
authors.forename: Tomomichi
authors.initials: T
authors.lastname: Sone
authors.affiliation: Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohta
authors.affiliation: Nihon Pharmaceutical University, Komuro 10281, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan. Electronic address: kitamura@nichiyaku.ac.jp.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D043182:Carboxylesterase / Q000378:metabolism; D002853:Chromatography, Liquid; D003993:Dibutyl Phthalate / Q000032:analysis / Q000378:metabolism*; D004051:Diethylhexyl Phthalate / Q000032:analysis / Q000378:metabolism*; D006868:Hydrolysis; D007421:Intestine, Small / Q000378:metabolism; D007527:Isoenzymes; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism; D010795:Phthalic Acids / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007527:Isoenzymes; D010795:Phthalic Acids; C024629:dimethyl phthalate; D003993:Dibutyl Phthalate; D004051:Diethylhexyl Phthalate; D043182:Carboxylesterase
keywords: Carboxylesterase; Hydrolytic metabolism; Phthalate; Rat liver microsomes; Rat small-intestinal microsomes; Substrate specificity