Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 7 No. 6 August 26, 2020 p.249-252
In vitro cytotoxicity of the thyrotoxic and hepatotoxic rubber antioxidant 2-mercaptobenzimidazole and its 4- or 5-methyl derivatives in rabbit corneal cells
  • Makoto Usami (Division of Pharmacology, National Institute of Health Sciences / Graduate School of Veterinary Medicine, Azabu University /
Yukie Kuroda 1) , Atsuko Miyajima 2) , Kazue Sakemi-Hoshikawa 1) , Makoto Usami 1) 3) , Katsuyoshi Mitsunaga 4) , Yasuo Ohno 1) 5) , Momoko Sunouchi 1)
1) Division of Pharmacology, National Institute of Health Sciences , 2) Division of Medical Devices, National Institute of Health Sciences , 3) Graduate School of Veterinary Medicine, Azabu University , 4) School of Pharmaceutical Sciences, Toho University , 5) Kihara Memorial Yokohama Foundation for the Advancement of Life Sciences
Keywords: Methyl-2-mercaptobenzimidazole, Cytotoxicity, SIRC cells

2-Mercaptobenzimidazole (MBI) and its methyl derivatives 4-methyl-MBI (4-MeMBI), 5-methyl-MBI (5-MeMBI), and 4(or 5)-methyl-MBI (4(5)-MeMBI) are widely applied industrial agents with substantial thyrotoxicity and hepatotoxicity detected in rats in vivo. Here, we examined the in vitro cytotoxicity of MBI and its derivates in cultured SIRC rabbit corneal cells. SIRC cells were cultured in the presence of the test chemicals for 72 hr, and cell viability was determined by estimating the number of cells using a crystal violet staining assay. The median lethal concentration (LC50) was calculated for each of the chemicals. The methyl derivatives showed higher cytotoxicity than MBI, which is in contrast to previous in vivo findings demonstrating higher thyrotoxicity and hepatotoxicity of MBI compared to its derivates. According to the LC50 values, the ranking of the tested agents in terms of cytotoxicity was 5-MeMBI (761.5 µM) ≥ 4-MeMBI (796.3 µM) ≥ 4(5)-MeMBI (822.9 µM) > MBI (1002.9 µM). The present results suggest that the lower thyrotoxicity and hepatotoxicity of methyl derivatives of MBI is related to their faster detoxification in vivo, because SIRC cells are considered to have lower drug-metabolizing activity than hepatic cells.