Plasma and tissue distribution of bismuth in normal and cirrhotic rats

Abstract

The effect of liver disease on total body handling of bismuth was studied in normal and cirrhotic rats to test the hypothesis that hepatic function can be a significant determinant of heavy metal handling. Excretion and tissue distribution of bismuth were investigated in animals administered bismuth subcitrate by the intramuscular route for 70 d. Plasma bismuth in control rats reached an apparent steady state of 31.89 ± 4.15 µg l^–1(mean ± standard error of mean, n= 12) by day 28–35. The plasma profile in cirrhotic rats resembled that of controls until day 42 after which bismuth concentrations became significantly elevated. At day 70 of dosing the mean plasma bismuth concentration was 63.68 ± 9.68 µg l^–1(n= 11) in cirrhotic rats compared with 32.68 ± 4.24 µg l^–1(n= 12) in control rats (p < 0.05). Total urinary excretion of cirrhotic animals closely paralleled that of controls; however, urinary bismuth clearance was significantly reduced beyond 42 d, as was faecal excretion. Bismuth tissue distribution was analysed in a randomly selected sub-set of control and cirrhotic animals. There was a significantly higher concentration of bismuth in the liver, bone, spleen, lungs and heart of the cirrhotic rats, with no change in the kidney. There was minimal accumulation of bismuth in the central nervous system of either normal or cirrhotic animals. Bismuth accumulation in cirrhotic rats suggests that patients with cirrhosis could be at risk from similar accumulation. Awareness of this potential risk suggests that monitoring of bismuth levels in patients with liver impairment may be an important part of dosage management and avoidance of toxicity. The application of these study processes to other metals which share common mechanisms of handling may result in better understanding of their potential for accumulation and clinical and population toxicity.