Madhyastha M S, Frohlich A A, Marquardt R R
Department of Animal Science, University of Manitoba Winnipeg, Canada.
Food Chem Toxicol. 1992 Aug;30(8):709-14. doi: 10.1016/0278-6915(92)90167-j.
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.
用大鼠进行的三项实验确定了膳食消胆胺对赭曲霉毒素A（OA）及其水解代谢产物α - 赭曲霉毒素（Oα）处置的影响。在第一个实验中，将OA（1毫克/千克）掺入含有0、0.5、1.0和2.0%消胆胺的饮食中。对于所有浓度的树脂，消胆胺均显著降低了OA的血药浓度（从1.6微克/毫升降至0.75微克/毫升，P<0.0001）。第二个实验表明，向大鼠饮食中添加2%消胆胺可显著降低OA的累积尿排泄量（从26微克降至6微克，P<0.01），并增加OA的累积粪排泄量（从8微克增至38微克，P<0.001）。第三个实验确定了在含有两种浓度（0和6%）饱和脂肪（牛脂）的饮食中添加消胆胺（2%）的效果。通过216小时血药浓度曲线下面积测定的OA生物利用度，对照组大鼠为424微克/毫升/小时，消胆胺处理组大鼠为186微克/毫升/小时（P<0.0001）。消胆胺处理使5天内粪便和尿液中OA加Oα的回收率从65.5%提高到96.2%（P<0.0001）。消胆胺还极大地增加了粪便中OA加Oα的量，尤其是OA的排泄量（从105微克增至160微克，OA加Oα的P<0.0001，OA的P<0.0001为82微克至150微克），并导致这些化合物在尿液中的排泄相应减少。饮食中脂肪浓度的影响远不如消胆胺显著，主要在尿液中检测到，且受与消胆胺相互作用的影响（P<0.0001）。当饮食中脂肪含量低时，消胆胺可大幅降低OA加Oα的浓度（37微克对8微克），但当脂肪含量高时，降低程度要小得多（19微克对12微克）。这些结果表明，饮食中脂肪浓度可能影响OA在尿液中的排泄模式。饮食中添加消胆胺可极大增加粪便中消除的OA量，减少尿液中的量，从而降低体循环中OA的含量。
