2, 5-Dihydroxy-4-methoxybenzophenone: a novel major in vitro metabolite of benzophenone-3 formed by rat and human liver microsomes. (June 2013)

• Record Type: Journal Article
• Authors: Kamikyouden, Nagisa; Sugihara, Kazumi; Watanabe, Yoko; Uramaru, Naoto; Murahashi, Tsuyoshi; Kuroyanagi, Masanori; Sanoh, Seigo; Ohta, Shigeru; Kitamura, Shigeyuki
• Is Part Of: Xenobiotica. Volume 43:Number 6(2013:Jun.)
• Page Start: 514
• Page End: 519
• Publication Date: 2013-06
• Subjects: Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.3109/00498254.2012.742217
• Languages: English
• ISSNs: 0049-8254

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>1. When benzophenone-3 (2-hydroxy-4-methoxybenzophenone; BP-3) was incubated with liver microsomes of untreated rats in the presence of NADPH, the 5-hydroxylated metabolite, 2, 5-dihydroxy-4-methoxybenzophenone (5-OH-BP-3), was formed as a major novel metabolite of BP-3. The 4-desmethylated metabolite, 2, 4-dihydroxybenzophenone (2, 4-diOH-BP), previously reported as the major <italic>in vivo</italic> metabolite of BP-3, was also detected. However, the amount of 5-OH-BP-3 formed <italic>in vitro</italic> was about the same as that of 2, 4-diOH-BP.</p> <p>2. The oxidase activity affording 5-OH-BP-3 was inhibited by SKF 525-A and ketoconazole, and partly by quinidine and sulfaphenazole. The oxidase activity affording 2, 4-diOH-BP was inhibited by SKF 525-A, ketoconazole and α-naphthoflavone, and partly by sulfaphenazole.</p> <p>3. The oxidase activity affording 5-OH-BP-3 was enhanced in liver microsomes of dexamethasone-, phenobarbital- and 3-methylcholanthrene-treated rats. The activity affording 2, 4-diOH-BP was enhanced in liver microsomes of 3-methylcholanthrene- and phenobarbital-treated rats.</p> <p>4. When examined recombinant rat cytochrome P450 isoforms catalyzing the metabolism of BP-3, 5-hydroxylation was catalyzed by P450 3A2, 1A1, 2B1, 2C6 and 2D1, while 4-desmethylation was catalyzed by P450 2C6 and 1A1.</p> </abstract>