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The role of lysosomes in the hepatic accumulation and release of beryllium

Biochemical Pharmacology
Publication Date
DOI: 10.1016/0006-2952(79)90405-2
  • Biology


Abstract The toxic metal beryllium (Be) can produce hepatic necrosis and is known to be concentrated by the liver after i.v. injection of particulate and soluble Be compounds. In the present study the accumulation and release of Be by a hepatic lysosome fraction of the rat has been examined after i.v. administration of sublethal doses of particulate Be phosphate (12.5 and 150 μmoles/kg) or the more hepatotoxic soluble BeSO 4 (12.5 and 25 μmoles/kg). Maximal lysosomal Be content is produced within 2 hr or 5 hr after the injection of Be phosphate or BeSO 4 respectively and in both cases this is followed by a gradual decrease in the lysosomal Be concentration of the next 7 days to 30–40 per cent of the maximal values, which is consistent with the loss of Be observed for whole liver. The release of Be from lysosomes has been examined by measurement in vitro of the liberation of Be into a suitable incubation medium from lysosomes prepared from Be treated animals. The results indicate that the liberation of Be was maximal for lysosomes isolated 5 hr after injection of either form of Be and was accompanied by a significant release of lysosomal β-glucuronidase activity, particularly at the higher doses of Be used, and therefore indicates that some loss of lysosomal integrity occurred. Rupture of the lysosomal membrane could not be demonstrated in vitro by incubation of lysosomes from untreated animals with externally added Be compounds. It is concluded, however, that any release of hydrolytic enzymes into the cytosol occurring in vivo may not be the major cause of cell necrosis produced by Be and it is suggested, therefore, that the role of lysosomes in Be hepatotoxicity is primarily in the intracellular accumulation and subsequent release of Be and that the main cytotoxic target for Be is probably extralysosomal.

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