Medline ® Abstracts for References 4,9,10
of 'Bleomycin-induced lung injury'
The cytotoxic agent bleomycin is feared for its induction of sometimes fatal pulmonary toxicity, also known as bleomycin-induced pneumonitis (BIP). The central event in the development of BIP is endothelial damage of the lung vasculature due to bleomycin-induced cytokines and free radicals. Ultimately, BIP can progress in lung fibrosis. The diagnosis is established by a combination of clinical symptoms, radiographic alterations, and pulmonary function test results, while other disorders resembling BIP have to be excluded. Pulmonary function assessments most suitable for detecting BIP are those reflecting lung volumes. The widely used transfer capacity of the lungs for carbon monoxide appeared recently not to be specific when bleomycin is used in a polychemotherapeutic regimen. There are no proven effective treatments for BIP in humans, although corticosteroids are widely applied. When patients survive BIP, they almost always recover completely with normalization of radiographic and pulmonary function abnormalities. This review focuses on BIP, especially on the pathogenesis, risk factors, and its detection.
Department of Internal Medicine, Sint Franciscus Gasthuis, Rotterdam, The Netherlands. firstname.lastname@example.org
Bleomycin-induced pulmonary endothelial cell injury: evidence for the role of iron-catalyzed toxic oxygen-derived species.
Martin WJ 2nd, Kachel DL
J Lab Clin Med. 1987;110(2):153.
Bleomycin, an effective cancer chemotherapeutic agent, is associated with serious pulmonary toxicity. As an in vitro model of bleomycin pulmonary toxicity, this study examined the ability of bleomycin to injure chromium 51-labeled bovine pulmonary artery endothelial (BPAE) cells in an 18-hour cytotoxicity assay. The data indicate that bleomycin-mediated injury to cultured BPAE cells can be quantified by 51Cr release, expressed as cytotoxic index (CI). Bleomycin-mediated injury to 51Cr-labeled BPAE cells (CI 19.4 +/- 1.6) could be significantly reduced by the iron chelator deferoxamine, 10(-3) mol/L (CI 7.5 +/- 1.1, P less than 0.001), but not by ethylenediaminetetraacetic acid, 10(-5) mol/L (CI 19.8 +/- 2.2). Similarly, bleomycin-mediated injury to BPAE cells (monitored by lactate dehydrogenase release) with a CI 27.1 +/- 4.8 could be reduced by 10(-3) mol/L deferoxamine to CI 10.5 +/- 2.6 (P less than 0.01). In contrast, hyperoxia (95% O2) accelerated bleomycin (1 to 100 mU/ml) toxicity to BPAE cells (P less than 0.01, all comparisons). This study suggests that bleomycin-induced injury of pulmonary endothelial cells may be dependent in part on two critical factors in the cellular environment: the availability of iron to the cell and the ambient O2 concentration.
Effect of iron deficiency on bleomycin-induced lung fibrosis in the hamster.
Chandler DB, Barton JC, Briggs DD 3rd, Butler TW, Kennedy JI, Grizzle WE, Fulmer JD
Am Rev Respir Dis. 1988;137(1):85.
Bleomycin produces a dose- and time-dependent interstitial pulmonary fibrosis in humans, and is widely used to produce an animal model for the study of interstitial pulmonary fibrosis. The mechanism(s) for bleomycin-induced pulmonary fibrosis is (are) unknown, but the production of oxygen radicals by a ferrous ion-molecular oxygen pathway might be related to the fibrosis. Therefore, we studied the effect of iron deficiency on the biochemical, inflammatory, and morphologic parameters of bleomycin-induced pulmonary fibrosis in the hamster. Mild iron deficiency was induced in hamsters by bleeding via the retro-orbital sinus and maintenance on an iron-deplete diet. After intratracheal administration of bleomycin (1 U), there was no accumulation of lung collagen in the iron-deficient bleomycin-treated animals. In comparison, iron-replete animals treated with bleomycin exhibited a significant (p less than 0.01) increase in lung collagen. In addition, bleomycin-treated iron-replete animals had increased lung lipid peroxidation (p less than 0.05), whereas bleomycin-treated iron-deficient animals did not (p greater than 0.05). Lung DNA and morphometric estimates of the lesion severity were significantly increased in both iron-replete and iron-deficient bleomycin-treated animals. These data indicate that iron deficiency is associated with a reduction in the severity of bleomycin-induced pulmonary fibrosis, possibly by the prevention of iron-catalyzed oxygen-radical formation and lipid peroxidation.
Department of Medicine, University of Alabama, Birmingham 35294.