Paradoxical effects of bleomycin and heavy water (D2O) in mice
| Autor: | Jean A. Laissue, Dominique Gaeng, Soren E. Larsen, Luis-Manuel Cruz-Orive, Hans Jörg Altermatt, Marianne Geiser, Thomas Schaffner |
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| Rok vydání: | 1995 |
| Předmět: |
Lung Diseases
congenital hereditary and neonatal diseases and abnormalities Cancer Research Pathology medicine.medical_specialty Pulmonary toxicity Radiation-Protective Agents Pharmacology Bleomycin Mice chemistry.chemical_compound Fibrosis In vivo medicine Animals Ingestion Drug Interactions Deuterium Oxide Lung Body fluid Mice Inbred BALB C Antibiotics Antineoplastic Dose-Response Relationship Drug urogenital system Body Weight Ovary nutritional and metabolic diseases Free Radical Scavengers Organ Size medicine.disease medicine.anatomical_structure Liver Oncology chemistry Toxicity Female |
| Zdroj: | Gaeng, D P, Geiser, M, Cruz-Orive, LM M, Larsen, S E, Schaffner, T, Laissue, J A & Altermatt, H J 1995, ' Paradoxical effects of bleomycin and heavy water (D 2 O) in mice ', International Journal of Cancer, vol. 62, no. 6, pp. 784-790 . https://doi.org/10.1002/ijc.2910620623 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.2910620623 |
| Popis: | Bleomycin (BLM) lacks many side effects of other cytostatic drugs. Pulmonary toxicity is the major dose‐limiting effect of BLM. This is based in part on generation of free radicals. It is conceivable that deuterium in body fluids lessens the production of free radicals, thus preventing or diminishing the morphologic expression of pulmonary BLM toxicity. We therefore studied the effect of moderate deuteration of body fluids on BLM‐induced lung damage in BALB/c‐mice. In addition to conventional histopathological methods, we used a vertical sectioning design for stereological estimation of pulmonary volumes and surface areas. BLM (low/medium/high dose: 25/50/75 IU/kg body weight) was injected i.p. once a week for 6 weeks. Half the mice drank deuterated water before, during and after BLM treatment. Three weeks after the last injection, the lungs were fixed by airway instillation. Deuterated animals treated with BLM lacked signs of irreversible BLM‐induced pulmonary damage. Conversely, focal sub‐pleural fibrosis and fibrosing alveolitis were present in BLM‐treated mice drinking tap water. Deuterated mice had stereological values for almost all lung parameters that were lower than in non‐deuterated mice. The organ‐specific advantage of deuteration was offset by marked enhancement of systemic toxicity of BLM. We conclude that (I) moderate concentrations of deuterium may prevent the development of fibrosing alveolitis in BLM‐treated mice, possibly by reducing proliferation of alveolar fibroblasts, and, less probably, by impairing generation or enhancing capture of free radicals; (2) the toxicity of BLM was enhanced by ingestion of deuterium, resulting in morphological liver alterations and increased mortality. © 1995 Wiley‐Liss, Inc. |
| Databáze: | OpenAIRE |
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