Subchronic exposure to individual and combined ochratoxin A and citrinin affects the expression of rat renal organic ani
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ORIGINAL ARTICLE
Subchronic exposure to individual and combined ochratoxin A and citrinin affects the expression of rat renal organic anion transporters Dean Karaica 1
&
Vedran Micek 2 & Dubravka Rašić 3 & Maja Peraica 3 & Maja Šegvić Klarić 4 & Davorka Breljak 1
Received: 26 February 2020 / Revised: 19 June 2020 / Accepted: 3 July 2020 # Society for Mycotoxin (Research Gesellschaft für Mykotoxinforschung e.V.) and Springer-Verlag GmbH Germany, part of Springer Nature 2020
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
Introduction Ochratoxin A (OTA) and citrinin (CIT) mycotoxins share significant nephrotoxic potential suspected to be the basis Dean Karaica and Vedran Micek contributed equally to this work. * Dean Karaica [email protected] 1
Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, Zagreb 10000, Croatia
2
Animal Breeding Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, Zagreb 10000, Croatia
3
Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, Zagreb 10000, Croatia
4
Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Schrottova 39/I kat, Zagreb 10000, Croatia
for the development of Balkan endemic nephropathy and urothelial tract tumors in humans and animals (EFSA 2012; EFSA 2020). OTA was found to increase reactive oxidative species (ROS) production (EFSA 2020), whereas CIT alters mitochond
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