Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 5 No. 3 June 19, 2018 p.113-116
In vitro metabolism of 4-methyl- and 5-methyl-2-mercaptobenzimidazole, thyrotoxic and hepatotoxic rubber antioxidants, in rat liver microsomes
  • Makoto Usami (Division of Pharmacology, National Institute of Health Sciences /
Atsuko Miyajima 1) , Yukie Kuroda 2) , Kazue Sakemi-Hoshikawa 2) , Makoto Usami 2) , Katsuyoshi Mitsunaga 3) , Tomohiko Irie 2) , Yasuo Ohno 2) 4) , Momoko Sunouchi 2)
1) Division of Medical Devices, National Institute of Health Sciences , 2) Division of Pharmacology, National Institute of Health Sciences , 3) School of Pharmaceutical Sciences, Toho University , 4) Kihara Memorial Yokohama Foundation for the Advancement of Life Sciences
Keywords: Methyl-2-mercaptobenzimidazole, Liver microsomes, Rat, In vitro metabolism, Cytochrome P450, SKF-525A

The metabolism of 4-methyl-2-mercaptobenzimidazole (4-MeMBI), 5-methyl-2-mercaptobenzimidazole (5-MeMBI), and 2-mercaptobenzimidazole (MBI) was examined in vitro in rat liver microsomes. The test chemicals were incubated in the presence of liver microsomes from male Sprague-Dawley rats, and their metabolism was analyzed by HPLC. The metabolism amount increased in an incubation time-dependent manner, and was similar among the test chemicals. SKF-525A, a non-selective inhibitor of cytochrome P450 (CYP) enzymes, decreased the metabolic rate of all the test chemicals, indicating the involvement of liver microsomal CYP enzymes. When liver microsomes from rats treated with CYP-inducers (β-naphthoflavone, phenobarbital, and isoniazid) were used, 4-MeMBI was more decreased than 5-MeMBI, particularly in the phenobarbital-treated group. These results, together with the reported inducibility of the drug-metabolizing activity by the test chemicals, partly explained the counteraction in the toxic effects between 4-MeMBI and 5-MeMBI in the in vivo study.