PT Unknown AU Abbas, Z TI Influence of quercetin on Ochratoxin A toxicokinetics and toxicity in F344 rats PY 2014 PU Christian-Albrechts-Universität zu Kiel WP https://macau.uni-kiel.de/receive/diss_mods_00015581 LA en DE Quercetin; Ochratoxin A; Toxikokinetik AB Subject of this work was to examine if dietary applicated quercetin influences OTA toxicokinetics and toxicity in growing male F344 rats. We stated the hypothesis, that co-administration of quercetin and OTA may increase delay of OTA excretion due to a competitive inhibition of both substances during elimination. In addition, we hypothesized, that the potent antioxidant quercetin diminishes OTA derived oxidative stress. Therefore, two experiments were conducted. In the first one, the two experimental groups (n = 9) received OTA added to the feed (10 mg/kg diet, daily intake of 0.6 mg/kg b.w.) of which one was supplemented with quercetin (100 mg/kg diet), additionally. OTA and the main metabolite OTα were measured in daily collected urine and feces, and in plasma, kidney, liver, brain and musculus quadriceps. Our results revealed, that 30 % of the totally consumed OTA was excreted with feces and urine mainly in the form of OTα. In the tissues, highest OTA-concentrations were found in plasma and in descending order in kidney/liver, muscle and brain. No significant differences were found between the animals who received OTA only, or OTA and quercetin. In the second experiment four groups (n = 12) received the basic diet (Control), supplemented with either 100 mg/kg quercetin (Quercetin) or 10 mg/kg OTA (OTA) or both. Feed consumption and body weight gain were measured. Animals receiving OTA suffered from reduced body weight gain due to reduced feed intake. Additional supplementation of quercetin did not improve this findings. Oxidative parameters were measured in plasma and in tissues. Our results on 8-iso-PGF2α, α-TOC and relative mRNA concentrations of HO-1 and SOD indicate that OTA induced oxidative stress in the kidney and quercetin was able to decrease relative HO-1 mRNA concentrations, but not any other parameter for oxidative stress we measured. In liver, no evidence for oxidative stress was obtained, but probably defence mechanism like Cu2+/Zn2+ SOD prevented the manifestation of OTA-induced oxidative stress. Our results on relative mRNA concentration analysis of the efflux transporter indicated an apical OTA transport mediated by intestinal BCRP and when OTA and quercetin were co-administered by MRP2. Also, renal P-gp was induced by OTA implicating P-gp mediated OTA secretion in the kidney. We concluded, that in respect of OTA toxicokinetics in vivo the competitive inhibition of intestinal resecretion and renal tubular secretion by quercetin and OTA, as shown in vitro, was overcome by the upregulation of intestinal and renal efflux transporters and that quercetin was able to diminish OTA-induced pro-oxidative effects on molecular level. PI Kiel ER