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Toxicologic Pathology
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Journal Article

Bleomycin-Induced Arthritis and Dermatitis in Rats

Michiyuki Kato

Drug Safety Administration Department, Daiichi Pharmaceutical Co., Ltd., 1-16-13 Kitakasai, Edogawa, Tokyo 134, Japan

Sanae Takada

Drug Safety Laboratory, Daiichi Pharmaceutical Co., Ltd., 1-16-13 Kitakasai, Edogawa, Tokyo 134, Japan

Yoshikazu Ish

Experimental Technology Research Center

We investigated the effect of the antitumor drug bleomycin (BLM) on synovial membrane and periarticular deep dermis in 10-wk-old young adult rats. BLM was found to induce edema, mononuclear cell infiltration and necrosis of the synovial membrane in the knee and tarsal joint, and inflammation in the deep dermis of the plantar hindfoot and digital pulvini in these rats after subcutaneous administration of 20 mg/kg for 3 days. After a 4-wk recovery period, foci of degenerative collagen bundles were observed in the deep dermis of the plantar hindfoot in spite of complete recovery of the lesions in the other dermal and synovial membrane sites. The synovitis was determined to begin with vesiculation of the macrophage-type lining cells, followed by edema and cell infiltration, especially near ligament insertion sites in the knee joint. The early dermal lesion consisted of dissociation of endothelial and subendothelial cells in small blood vessels thought to be postcapillary venules, edema, and monocyte infiltration. The severity of arthritis was greater in young adults than juvenile rats. From these results, BLM was shown to have a toxic effect on synovial lining cells and to induce inflammation in the synovial membrane and periarticular dermis.

Key Words: Bleomycin • antitumor drug • arthritis • dermatitis • rat

Toxicologic Pathology, Vol. 25, No. 6, 549-555 (1997)
DOI: 10.1177/019262339702500603
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