Inhibitory effect of magnolol on Trp-P-2-induced DNA damage in various organs in mice.
Magnolol has been reported to strongly inhibit the mutagenicity induced by indirect mutagens in the Ames test as well as the clastogenicity induced by benzo(a)pyrene (B(a)P) in the mice micronucleus test. Here, we evaluated the inhibitory effect of magnolol on the DNA damage induced by 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) in various organs using the mice alkaline single cell gel electrophoresis (SCG) assay. Animals were treated with a single oral administration of magnolol (0.01, 0.1, 1, 10, and 100 mg/kg), followed by a single intraperitoneal injection of Trp-P-2 (10 mg/kg). The liver, lung, and kidney were removed at 3 h after treatment and used in SCG assay. The results indicated that magnolol inhibited Trp-P-2-induced DNA damage in various organs. To elucidate the mechanism of this inhibitory effect against Trp-P-2, we investigated the inhibitory effect of magnolol on in vivo CYP1A2 activity using the zoxazolamine paralysis test. Magnolol significantly prolonged zoxazolamine paralysis time and showed an inhibitory effect on in vivo CYP1A2 activity. These results indicate that magnolol has an inhibitory effect on the DNA damage induced by Trp-P-2 in various organs in vivo. This inhibitory mechanism is considered due to in vivo CYP1A2 inhibition.
Saito
Junichiro
J
Drug Safety Research Laboratories, Astellas Pharma Inc. 2-1-6, Kashima, Yodogawa-ku, Osaka, 532-8514, Japan. junichiroh.saitoh@jp.astellas.com
Fukushima
Hiroko
H
Nagase
Hisamitsu
H
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002243:Carbolines / Q000633:toxicity*; D020552:Comet Assay; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D004249:DNA Damage; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009153:Mutagens / Q000633:toxicity*; D015049:Zoxazolamine / Q000494:pharmacology
D016587:Antimutagenic Agents; D001713:Biphenyl Compounds; D002243:Carbolines; D017705:Lignans; D009153:Mutagens; C005498:magnolol; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D015049:Zoxazolamine; D019388:Cytochrome P-450 CYP1A2