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Inhibitory effect of magnolol on Trp-P-2-induced DNA damage in various organs in mice
Junichiro Saito1, Hiroko Fukushima, Hisamitsu Nagase
1Drug Safety Research Laboratories, Astellas Pharma Inc. 2-1-6, Kashima, Yodogawa-ku, Osaka, 532-8514, Japan. junichiroh.saitoh@jp.astellas.com
Abstract:
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.
Insights
Magnolol effectively inhibits DNA damage caused by Trp-P-2 in mouse organs. This protective effect is linked to magnolol
Area of Science:
- Pharmacology
- Toxicology
- Molecular Biology
Background:
- Magnolol demonstrates inhibitory effects against mutagenicity and clastogenicity.
- Previous studies highlight magnolol's protective role in genotoxicity assays.
- The genotoxic compound 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) is a known inducer of DNA damage.
Purpose of the Study:
- To evaluate magnolol's inhibitory effect on Trp-P-2-induced DNA damage in various mouse organs.
- To investigate the underlying mechanism of magnolol's protective action against Trp-P-2 genotoxicity.
- To assess magnolol's impact on in vivo cytochrome P450 1A2 (CYP1A2) activity.
Main Methods:
- Mice were administered varying doses of magnolol orally, followed by intraperitoneal injection of Trp-P-2.
- DNA damage was assessed in liver, lung, and kidney tissues using the alkaline single cell gel electrophoresis (SCG) assay.
- In vivo CYP1A2 activity was evaluated using the zoxazolamine paralysis test.
Main Results:
- Magnolol significantly inhibited Trp-P-2-induced DNA damage across multiple organs.
- Magnolol administration led to a prolonged zoxazolamine paralysis time.
- These findings indicate that magnolol inhibits in vivo CYP1A2 activity.
Conclusions:
- Magnolol effectively mitigates Trp-P-2-induced DNA damage in vivo.
- The inhibitory mechanism is attributed to magnolol's suppression of CYP1A2 activity.
- Magnolol shows potential as a protective agent against specific types of genotoxicity.
