Pulmonary toxicity of the combination of bleomycin and peplomycin--an experimental study in rats.

Combination of the two drugs bleomycin (BLM) and peplomycin (PEP) may enhance their antineoplastic effects; however, it is not known as to whether this enhancement is accompanied by a concomitant increase in toxicity, especially toxic lung damage. A histologic and stereologic investigation was carried out to compare the pulmonary toxicity of BLM, PEP, and a combination of the two drugs in animals. A total of 180 female Wistar rats were randomly assigned to 4 groups: 45 animals were treated with daily i.p. injections of 4 mg/kg BLM, 45 rats received 2.5 mg/kg i.p. PEP daily, 45 animals were given i.p. injections of a combination of 2.5 mg/kg BLM and 1 mg/kg PEP, and 45 rats received 1 ml 0.9% NaCl solution. Histological examination of the lungs demonstrated varying degrees of exudative and fibrosing alveolitis in animals treated with BLM, PEP, and BLM-PEP. Stereological analysis revealed a significant thickening of the alveolar wall after 20-60 days and a significant decrease in the surface density of alveolar walls after 40-60 days in all treated groups. Both histological examination and stereological parameters indicated more pronounced inflammatory changes in the alveolar walls and a prior loss of alveolar surface after 20 and 30 days in animals receiving PEP and PEP-BLM as compared with those undergoing BLM treatment. After 40-60 days, during which time irreversible fibrotic changes prevailed, significant stereological differences between the three treated groups could not be detected. Thus, our experimental observations did not show any potentiation of the toxic pulmonary effect of BLM and PEP following their combined administration.