Aylalox metabolites in human urine and liver in Zambia

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Dil, Lee Ann Gage
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Aflatoxins are believed by many investigators to play a major role in the etiology of primary hepatocellular carcinoma (PHC). As PHC is the commonest tumour of men in Zambia, investigation of aflatoxin exposure of the Zambian population is warranted. Previous studies in Zambia have shown that aflatoxins are present in certain foods and confirmation of consumption was obtained from a study demonstrating the presence of / aflatoxin metabolites in human urine. /In this study urine samples were collected from patients with and without liver disease admitted to the University Teaching Hospital in Lusaka, in an attempt to examine the possible effect of liver pathology on the type and amount of aflatoxin metabolite(s) excreted. No significant differences were observed. The present study was therefore carried out to investigate this relationship in more depth. Studies have shown that conjugation reactions play an important role in aflatoxin metabolism in animals although the amount and type of aflatoxin conjugates in humans is not known. Thus urine samples, from patients with and without liver disease,were collected for one year and analysed for both free and conjugated aflatoxin metabolites. The incidence of urinary aflatoxin excretion in liver disease and control patients was 3.7 per cent with a mean concentration of 9.1 ng/ 100 ml. Aflatoxins BI , MI and aflatoxicol (AFL) were detected. No significant differences were observed between the two groups of patients although aflatoxins were seen more frequently and at greater concentrations in urine of control patients. This may suggest that patients with liver disease have an impaired ability to metabolize and excrete aflatoxin. IV aflatoxin studies, serum and liver samples were analysed for HBV markers. The HBV carrier state in this study was observed to be exceedingly high: 32 per cent of control patients were shown to have hepatitis B virus surface antigen in their serum. No relationship between the presence of HBV markers, aflatoxin metabolites excreted, and PHC was observed. It was noted, however, that patients excreting aflatoxin also had evidence of HBV infection. A longitudinal, prospective study should now be carried out to investigate the possible interactions of these two factors more closely. VI Glucuronide and sulphate conjugates of aflatoxins MI , PI and AFL were looked for. Surprisingly, no conjugated metabolites were detected, even in patients excreting up to 20 ng of free aflatoxin /100 ml urine. This suggests that these conjugation reactions do not play a major role in aflatoxin metabolism in humans. The urinary survey was extended to a rural hospital in the Eastern Province. Consumption of aflatoxin was observed to be more of a problem there, where urinary aflatoxins were detected significantly more often (incidence = 15.4 per cent) and at greater concentrations (mean = 16.5 ng /100 ml). Liver tissues, taken at autopsy from subjects with and without liver disease, were also examined for aflatoxin metabolites. Only aflatoxin B. was observed, at concentrations of 0.3-9.5 ng/g. Most of the samples were from controls and therefore the effect of liver pathology on the type and/or amount of aflatoxin metabolite(s) observed could not be assessed. However, the liver of one PHC subject was included and was found to contain over 10 times more aflatoxin than the highest level observed in controls. The results of the urinary and liver studies were tabulated according to age, sex and season. Aflatoxin was detected significantly more often (P <0.05) in livers obtained from males than females and, in Lusaka, only urine samples collected from males were positive for aflatoxin. It was found that the likelihood of consuming aflatoxin was significantly higher in the rainy season than the dry season (P <0.05). It is generally believed that both aflatoxin and hepatitis B virus (HBV) influence the incidence of PHC. Therefore, concurrent with
Aflatoxins , Liver--Metabolism