Interactions of Organic Anion Transporters and Organic Cation Transporters With Mycotoxins

Abstract

Abstract. 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, α-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.

Interactions of Human Organic Anion Transporters With Aristolochic Acids

“…[ Other materials used in this study were the same as those previously reported (11). AAs were subjected to preparative high-performance liquid chromatography (HPLC) to obtain AA-I (22 mg) and AA-II (19 mg) and were identified by comparing 1 H-nuclear magnetic resonance spectroscopy and mass spectrometry spectral data with reported data (12).…”

“…Uptake experiments using S2 hOATs (S2 hOAT1, S2 hOAT2, S2 hOAT3, and S2 hOAT4) were performed as previously described (11). For kinetic analysis, S2 hOAT1 and S2 hOAT3 were incubated at 37˚C in a solution containing either [ 14 C]PAH (hOAT1) or [ 3 H]ES (hOAT3) at different concentrations in the absence or presence of AA-I for 2 min.…”

Possible Role of Phosphatidylcholine and Sphingomyelin on Fumonisin B1-mediated Toxicity

“…Interactions of FB1 with organic anion transporter of rat (rOAT1) 45) and of human (hOAT3) 46) were reported in the inhibition study using typical substrates. These data suggest the possibility of efficient uptake in liver and reuptake in kidney of FB1 through OAT family of transporters.…”

Causes and Consequences of Variability in Drug Transporter Activity in Pediatric Drug Therapy

“…Finally, environmental chemicals, such as diesel exhaust particle extract and pesticides, have been demonstrated to interact with drug transporters through competitive mechanisms or to modify their expression (Table ) . Data are still sparse, and additional in vitro and in vivo studies are required to quantify pollutant‐transporter interplays.…”