title: Cytotoxicity of benzyl isothiocyanate in normal renal proximal tubular cells and its modulation by glutathione.
abstract: In the present study, we examined the toxicity of benzyl ITC (BITC) and its urinary mercapturic acid metabolite (BITC-NAC), using a normal renal proximal tubular cell line, pig LLC-PK1. BITC increased cell death with an IC(50) value of about 7 μM, whereas the cytotoxic effect of BITC-NAC was five times weaker than that of BITC. We observed a significant necrosis of the compounds on LLC-PK1 cells with oxidative stress. In the presence of 5 mM glutathione (GSH), comparable to physiological levels, the cytotoxicity of BITC-NAC as well as BITC was significantly reduced. Furthermore, the increase in intracellular GSH levels by pretreatment with NAC before the BITC treatment resulted in inhibition of the BITC-induced necrotic events as well as intracellular oxidative stress. These results suggest that GSH is a determinant of cellular resistance against the BITC-mediated and oxidative stress-dependent cytotoxicity in renal proximal tubular cells.
authors.affiliation: Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Abe
authors.forename: Masashi
authors.initials: M
authors.lastname: Okuhira
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tsutsui
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Murata
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D005978:Glutathione / Q000494:pharmacology*; D017879:Isothiocyanates / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects*; D009336:Necrosis; D018384:Oxidative Stress; D013552:Swine
chemical_list: D017879:Isothiocyanates; C031403:benzyl isothiocyanate; D005978:Glutathione; D000111:Acetylcysteine