Effects of Pretreatment of Hep G2 Cells with β-Naphthoflavone on Cytotoxicity of Propranolol and its Active Metabolite 4-Hydroxypropranolol

• Published in: Journal of Health Science 2003, Vol.49 (4), p.292-297
• Main Authors: Junko Miyanoa, Harumi Motoyamaa, Masako Fukuokaa, Shigeo Yamamotob, Shizuo Narimatsua, Kenichiro Ogurac, Tadashi Watabec, d, Masuhiro Nishimurae, Nobuhiko Uedae, Shinsaku Naitoe
• Format: Article
• Language: Japanese
• ISSN: 1344-9702

Cytotoxicities of propranolol (PL) and its active metabolite, 4-hydroxypropranolol (4-OH-PL), were examined in a human hepatoma cell line, Hep G2. Hep G2 cells were cultured in the presence of β-naphthoflavone (BNF, 25 or 50 μM), lansoprazole (LPZ, 25 or 50 μM) or 0.5% dimethylsulfoxide (vehicle) for 48 hr. The cells were harvested, and microsomal and cytosolic fractions were prepared by differential centrifugation methods. Various enzyme activities were determined as follows:microsomal 7-ethoxyresorufin (ER) O-deethylation as a CYP1A1 index, microsomal phenacetin (PN) O-deethylation as a CYP1A2 index, microsomal and cytosolic p-nitrophenyl acetate (NPA) hydrolysis as a carboxylesterase index and cytosolic 4-OH-PL sulfation as a sulfotransferase index. The pretreatment of Hep G2 cells with LPZ or BNF increased microsomal ER O-deethylase activities, and the potency of BNF was much higher than that of LPZ. Cytosolic 4-OH-PL sulfation was also elevated by the pretreatment with BNF but not with LPZ. Microsomal PN O-deethylase activity was not detectable in either the control or BNF-pretreated group under the conditions used. Microsomal and cytosolic NPA hydrolase activities were similar between the control and the BNF-pretreated groups.