Dietary Cholestyramine Reduces Ochratoxin a-Induced Nephrotoxicity in the Rat by Decreasing Plasma Levels and Enhancing Fecal Excretion of the Toxin

Abstract

Ochratoxin A (OTA) is a mycotoxin that may contaminate animal feed (oat, barley, and rye) and food (wheat, rice, coffee, beer, pig meat), leading to major health problems (e.g., nephropathy) in several animal species including humans. Several methods have been tested to reduce the toxicity of OTA in animals but with limited success. In rats, the effect of cholestyramine (CHA), a bile acid-binding resin, was investigated on OTA-induced nephrotoxicity and bioavailability. Animals were fed semisynthetic diets containing two levels of OTA: 1 or 3 ppm. At each level of OTA, the diets were enriched with 0.1, 1, and 5% of CHA. The results showed that CHA decreased the concentration of OTA in plasma. At 1 and 3 ppm of OTA in the diet, CHA is effective at a level of 0.1% and 5%, respectively. The excretion of OTA and its metabolites (ochratoxin alpha and hydroxylated ochratoxin A) in bile and urine was also decreased by addition of 5% CHA in the diet. This was associated with an increase of OTA excretion in feces. Enzymuria and renal morphology revealed that dietary CHA can decrease OTA-induced nephrotoxicity, probably by reducing renal exposure to the toxin. In conclusion, CHA can reduce OTA concentrations in plasma as well as reducing nephrotoxicity, which may be attributed to a decrease of bioavailability and/or enterohepatic circulation of the toxin.

A Review of the Mechanism of Injury and Treatment Approaches for Illness Resulting from Exposure to Water‐Damaged Buildings, Mold, and Mycotoxins

“…Animal studies involving the use of CSM for OTA exposure have shown it accomplishes the therapeutic goal of reducing plasma levels of OTA while enhancing fecal excretion of the toxin bound to CSM. A study was able to demonstrate decreased nephrotoxicity in rats exposed to OTA that were given CSM, by reducing plasma and urine values of OTA while increasing fecal excretion [179, 180]. An in vitro study showed the CSM had a higher affinity for OTA than bile salts and it was proposed that, in addition to effects on the enterohepatic circulation of OTA, alteration of the biliary bile salt pool may be a means in which CSM reduces OTA toxicity [181].…”