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Individual and combined subchronic oral exposure to ochratoxin A and citrinin affect the expression of organic cation transporters in rat kidney

Previous studies have shown that transporters for both organic anions (Oat) and organic cations (Oct) provide a possible entrance pathway for mycotoxins including ochratoxin A (OTA) and citrinin (CIT) having the nephrotoxic effects in mammals. However, compared to Oats, individual and combined exposure effects of these mycotoxins on Oct expression in mammalian kidney is still unknown. Here, we used immunofluorescence microscopy and Western blot analysis to investigate individual and combined effects of OTA (0.125 and 0.250 mg/kg b.w.) and CIT (20 mg/kg b.w.) exposure on renal localization and protein expression of rat Oct (rOct1 and rOct2) following 21-day subchronic oral exposure of Wistar rats. In addition, we have studied the potential protective effects of resveratrol (RSV) (20 mg/kg b.w.) on renal localization and protein expression of studied rOcts. Results showed that protein expression of rOct1 (but not rOct2) was significantly downregulated by both individual OTA doses used in this study. Combination of both mycotoxins (OTA+CIT) had a downregulating effect exclusively on the rOct1 protein expression when the higher experimental OTA dose (0.250 mg/kg b.w.) was used. In individual manner, citrinin did not affect the expression of both rOct1 and rOct2 proteins. Interestingly, the combination of tested mycotoxins (OTA+CIT) and RSV caused a significant decrease of renal rOct1 and rOct2 protein expression. In conclusion, OTA has an Oct- and dose-dependent effect on the protein expression of studied rOcts whereas RSV does not protect, but potentially enhances the nephrotoxic effects of studied mycotoxins in rat kidneys. (Croatian Science Foundation project IP-09-2014-5982).

kidney, mycotoxins, organic cations, proximal tubules, resveratrol, Wistar rat

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