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

Abstract

Three experiments with rats established the effects of dietary cholestyramine on the disposition of ochratoxin A (OA) and its hydrolysed metabolite, α-ochratoxin (Oα). 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 μg/ml, P < 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 μg, P < 0.01) and increased cumulative faecal OA excretion (8 to 38 μg, P < 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 μg/ml/hr for the control rats and 186 μg/ml/hr for the cholestyramine-treated rats ( P < 0.0001). Cholestyramine treatment increased the recovery of OA plus Oα in the faeces plus urine over a 5-day period from 65.5 to 96.2% ( P < 0.0001). Cholestyramine also greatly increased the amount of OA plus Oα and particularly of OA excretion in the faeces (105 to 160 μg, P < 0.0001 for OA plus Oα and 82 to 150 μg, P < 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 < 0.0001). Cholestyramine greatly reduced the concentration of OA plus Oα (37 v. 8 μg) when the content of dietary fat was low but to a much lesser degree when it was high (19 v. 12 μg). 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.