The action of azapropazone, oxyphenbutazone and phenylbutazone on lysosomes

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Abstract
Azapropazone, oxyphenbutazone and phenylbutazone have a stabilizing action on isolated lysosomes over a wide concentration range but a lytic action at high concentrations. The lytic action of phenylbutazone was greater than the other drugs. Phenylbutazone at a high concentration was found to accelerate the breakdown of lysosomes in isolated stomach preparations in vitro. Phenylbutazone was found to have a greater ulcerogenic action than azapropazone in rats and rabbits. Tissues removed from rats and rabbits dosed with phenylbutazone showed evidence of lysosomal damage when examined histochemically for acid phosphatase. In contrast, tissues from control and azapropazone-treated rats showed no evidence of lysosomal damage. Sections of rat gut incubated with azapropazone and phenylbutazone in vitro showed similar results. The possibility is discussed that drugs in high concentration may damage lysosomes in the gastrointestinal tract. It is suggested that lysosomal damage may contribute to the ulcerogenic action of the drugs in vivo.

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