Pulmonary Toxicity After Treatment With Bleomycin Alone or in Combination With Hyperoxia

Abstract

Female Wistar rats (n = 11) received bleomycin 10 mg kg-1 i.p. three times weekly for 6 weeks. Four weeks later part of the group (n = 7) were exposed to 50% oxygen in air for 4 h; the others served as unexposed controls. A further control group (n = 5) received physiological saline i.p. and was not exposed to oxygen. One week after the hyperoxia treatment all animals were sacrificed and the lungs prepared for histological and biochemical determinations. Although the average body weight of the bleomycin-treated rats decreased significantly compared with the saline-treated controls, no significant alterations in lung histology were found in regard to the occurrence of oedema, fibrosis, and type II pneumocytes. Intra-alveolar macrophages were significantly increased. Subsequent hyperoxia did not lead to a more pronounced effect, except for macrophage accumulation. The activities of superoxide dismutase and glutathione peroxidase were not changed either after administration of bleomycin alone or after combination with hyperoxia. It is concluded that bleomycin i.p. in doses comparable to those encountered clinically, administered alone or combined with hyperoxia, does not result in pulmonary damage in female Wistar rats.

Possible Modulatory Role of Nitric Oxide in Lung Toxicity Induced in Rats by Chronic Administration of Bleomycin

“…In the current investigation, it was found that BLM did not affect either parameter significantly, notwithstanding its effect on lipid peroxidation. Similar findings have been provided by Blom-Muilwijk et al [14], who reported no change in GSH-Px activity after BLM. In contrast to these findings, however, Karam et al [10]and Phan and Fantone [38]reported an increase in pulmonary GSH-Px activity and a reduced cell content of GSH after BLM administration.…”

“…In the literature, many experimental protocols have been utilised to induce lung toxicity with BLM, including frequent systemic intraperitoneal injections over long periods of time. The doses of BLM and the frequency of administration as well as the duration of treatment performed in this study have been previously employed by other investigators [14, 15]. It has been reported that after chronic exposure to BLM, body weight loss [14, 33]and an increase in the lung weight/body weight ratio [9, 17]are signs of lung toxicity.…”

“…The doses of BLM and the frequency of administration as well as the duration of treatment performed in this study have been previously employed by other investigators [14, 15]. It has been reported that after chronic exposure to BLM, body weight loss [14, 33]and an increase in the lung weight/body weight ratio [9, 17]are signs of lung toxicity. Furthermore, in the present investigation, there was a decreased activity of ACE as well as elevated HP and LP levels in the lung tissue, which are all further evidence of pulmonary toxicity.…”

“…Indeed, many experimental protocols can be performed to provoke lung toxicity with BLM that end with fibrotic changes. Such pulmonary toxicity has been demonstrated after repeated systemic intraperitoneal [14, 15]and subcutaneous [16, 17]injections, as well as after a single local intratracheal instillation [2, 18, 19]of BLM.…”

Bleomycin-Induced Pneumonitis

“…Because bleomycin is assumed to induce its toxicity partially by the induction of free radicals, the administration of high inspired oxygen could be hazardous. In most studies 64,77,78 carried out in animals, such a relation has been shown. For instance, in hamsters treated with bleomycin and 70% oxygen for 72 h, the mortality was 90% compared with 15% in those animals that received bleomycin only.…”