Effect of dietary cholestyramine on the elimination pattern of ochratoxin A in rats

Three experiments with rats established the effects of dietary cholestyramine on the disposition of ochratoxin A (OA) and its hydrolysed metabolite, alpha-ochratoxin (O alpha). In the first experiment OA (1 mg/kg) was incorporated into a diet that contained 0, 0.5, 1.0 and 2.0% cholestyramine. Cholestyramine markedly reduced blood concentrations of OA (1.6 to 0.75 micrograms/ml, P less than 0.0001) for all concentrations of the resin. The second experiment demonstrated that 2% cholestyramine added to the diet of rats markedly reduced cumulative urinary OA excretion (26 to 6 micrograms, P less than 0.01) and increased cumulative faecal OA excretion (8 to 38 micrograms, P less than 0.001). The third experiment established the efficacy of cholestyramine (2%) when added to diets containing two concentrations (0 and 6%) of a saturated fat (tallow). The bioavailability of OA as determined by area under the blood concentration curve over 216 hr was 424 micrograms/ml/hr for the control rats and 186 micrograms/ml/hr for the cholestyramine-treated rats (P less than 0.0001). Cholestyramine treatment increased the recovery of OA plus O alpha in the faeces plus urine over a 5-day period from 65.5 to 96.2% (P less than 0.0001). Cholestyramine also greatly increased the amount of OA plus O alpha and particularly of OA excretion in the faeces (105 to 160 micrograms, P less than 0.0001 for OA plus O alpha and 82 to 150 micrograms, P less than 0.0001 for OA) and resulted in a corresponding decrease in the excretion of these compounds in the urine. The concentration of fat in the diet had a much less dramatic effect than cholestyramine, was mainly detected in the urine and was affected by an interaction with cholestyramine (P less than 0.0001). Cholestyramine greatly reduced the concentration of OA plus O alpha (37 v. 8 micrograms) when the content of dietary fat was low but to a much lesser degree when it was high (19 v. 12 micrograms). These results suggest that the concentration of fat in the diet may affect the pattern of OA excretion in the urine. Cholestyramine added to the diet greatly increases the amount of OA eliminated in the faeces and reduces the amount in the urine, and as a result it decreases the amount present in the systemic circulation.