Inhibition of dexamethasone-induced cytochrome P450-mediated mutagenicity and metabolism of aflatoxin B1 by Chinese medicinal herbs.
Oldenlandia diffusa (OD) and Scutellaria barbata (SB) have been used in traditional Chinese medicine for treating liver, lung and rectal tumours. We previously showed that they inhibited mutagenesis, DNA binding and metabolism of aflatoxin B1 (AFB1) and benzo(a)pyrene (BaP) bioactivated by Aroclor 1254-induced rat S9. The purpose of this study was to investigate the effects of OD and SB on the mutagenicity of AFB1 in Salmonella typhimurium TA100 using dexamethasone (DXM)-induced rat hepatic S9, on cytochrome P450-linked aminopyrine N-demethylase (APND) activity in DXM-induced hepatic microsomes and on the metabolism of AFB1 by DXM-induced S9 using high-performance liquid chromatography (HPLC). The experimental results showed that OD and SB consistently inhibited the mutagenicity of AFB1 bioactivated by either non-induced or DXM-induced S9. These effects correlated with the inhibition of cytochrome P450-linked APND activity in DXM-induced microsomes and with an inhibition of DXM-induced S9 mediated metabolism of [3H]AFB1 as determined by HPLC. Since DXM treatment has been associated with an induction of the CYP3 enzyme family, these results suggest that OD and SB may possess antimutagenic and antitumorigenic activity towards AFB1 through an inhibition of CYP3-mediated metabolism of AFB1.
Wong
B Y
BY
Department of Natural Science, Graduate School, Loma Linda University, CA 92350.
Lau
B H
BH
Yamasaki
T
T
Teel
R W
RW
D016604:Aflatoxin B1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016607:Aflatoxin M1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000348:Aflatoxins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000633:Aminopyrine N-Demethylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D016296:Mutagenesis / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000348:Aflatoxins; D016587:Antimutagenic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D011506:Proteins; C042410:aflatoxin P1; C033759:aflatoxin Q1; D016607:Aflatoxin M1; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D000633:Aminopyrine N-Demethylase