Interactions of organic anion transporters and organic cation transporters with mycotoxins.
Mycotoxins are secondary metabolites of moulds that which exert adverse effects in humans and animals. It is known that direct cellular toxicity is often associated with increased cellular accumulation of toxic compounds, and membrane transport may be the first fundamental stage in the development of the cytotoxicity. To elucidate the entry pathway for mycotoxins into cells, we have investigated the interactions of human and rat organic anion transporters (hOATs/rOats) and human organic cation transporters (hOCTs) with mycotoxins using cells stably expressing hOATs/rOats/hOCTs. The mycotoxins tested were aflatoxin B1, alpha-zearalenol, citrinin, citrioveridine, cyclopiazonic acid, fumonisin B1, gliotoxin, patulin, penicillic acid, rubratoxin B, and zearalenone. These mycotoxins inhibited organic anion uptake mediated by hOAT1-4, and organic cation uptake mediated by hOCT1-2. By comparing the IC(50) values of mycotoxins for hOATs, it was found that hOAT1 and hOAT3 exhibited higher affinity interactions with mycotoxins than hOAT2 and hOAT4. There was no interspecies difference between humans and rats for the interactions of OATs with mycotoxins except that of OAT3 with rubratoxin B. Finally, we observed that hOAT1-4 and hOCT1-2 mediated the uptake of aflatoxin B1. In conclusion, hOATs and hOCTs interacted with various mycotoxins. Considering the localization of hOATs/rOats and hOCTs, it was suggested that these transporters were the possible entrance pathway for mycotoxins in kidney and liver, leading to the induction of adverse effects in humans and rats.
Tachampa
Kittipong
K
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Japan.
Takeda
Michio
M
Khamdang
Suparat
S
Noshiro-Kofuji
Rie
R
Tsuda
Minoru
M
Jariyawat
Surawat
S
Fukutomi
Toshiyuki
T
Sophasan
Samaisukh
S
Anzai
Naohiko
N
Endou
Hitoshi
H
D016604:Aflatoxin B1 / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009183:Mycotoxins / Q000493:pharmacokinetics / Q000633:toxicity*; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors* / Q000502:physiology; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D013045:Species Specificity
D009183:Mycotoxins; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D016604:Aflatoxin B1