Subchronic exposure to individual and combined ochratoxin A and citrinin affects the expression of rat renal organic anion transporters

Mycotoxin Res. 2020 Nov;36(4):339-352. doi: 10.1007/s12550-020-00399-4. Epub 2020 Jul 11.

Abstract

Ochratoxin A (OTA) and citrinin (CIT) are mycotoxins known to co-contaminate human/animal food/feed. Their prominent nephrotoxic effects pose a threat to human and animal health. Studies have shown synergistic or additive effects of these two mycotoxins, but a clear consensus on this phenomenon does not exist. In vitro/vivo studies on OTA and CIT effects showed they elevate oxidative stress parameters. Some in vitro studies tested resveratrol (RSV) as a potential antioxidant to counteract these OTA and CIT effects. However, data on the combined effects of OTA + CIT mycotoxins and RSV on their in vivo toxicity is lacking. We used immunofluorescence microscopy and Western blotting to study the subchronic effects of individual/combined OTA (0.125 and 0.250 mg kg-1 b.w.) and CIT (20 mg kg-1 b.w.) on the localization/expression of rat renal organic anion transporters (rOats) (rOat1/Slc22a6, rOat2/Slc22a7, rOat3/Slc22a8, rOat5/Slc22a19) that mediate the secretion/reabsorption of organic anions in kidney proximal tubules. We investigated if RSV (20 mg kg-1 b.w.) can counteract the effects of both mycotoxins on the localization/expression of studied transporters. Results revealed Oat- and dose-dependent changes in protein expression of rOats. When combined with both mycotoxins, RSV decreased the protein expression of all of the studied rOats. Its effect was additive on Oat1/2/5. Thus, RSV failed to ameliorate OTA- and/or CIT-related nephrotoxic effects on the expression of studied rOats in rat kidneys.

Keywords: Kidney; Mycotoxins; Oral exposure; Organic anions; Proximal tubules; Resveratrol.

MeSH terms

  • Animals
  • Citrinin / administration & dosage*
  • Kidney / drug effects*
  • Male
  • Ochratoxins / administration & dosage*
  • Organic Anion Transporters / genetics*
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar

Substances

  • Ochratoxins
  • Organic Anion Transporters
  • ochratoxin A
  • Citrinin