Direct toxic effect of bleomycin on alveolar type 2 cells

Karam, Heba M.; Hurbain-Kosmath, I; Housset, B.

doi:10.1016/0378-4274(94)03207-n

Cited by 15 publications

(11 citation statements)

References 25 publications

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“…Previous studies in cell systems employing either chelating agents or iron-deficient growth media to deplete iron are mixed in their conclusions regarding the requirement for iron in bleomycin growth inhibitory activity [32][33][34][35][36][37]. HL-60 cells grown in iron-depleted medium displayed a decrease in bleomycin-mediated growth inhibition and DNA damage [38].…”

Section: Discussionmentioning

confidence: 98%

The iron chelating cardioprotective prodrug dexrazoxane does not affect the cell growth inhibitory effects of bleomycin

Patel

Hasinoff

2004

Journal of Inorganic Biochemistry

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Section: Discussionmentioning

confidence: 98%

The iron chelating cardioprotective prodrug dexrazoxane does not affect the cell growth inhibitory effects of bleomycin

Patel

Hasinoff

2004

Journal of Inorganic Biochemistry

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“…Crucial participation of the latter has been reinforced by the observation that hyperoxia enhances the pulmonary toxicity [17], while hypoxia ameliorates it [35]. It has been proposed that the cellular toxicity and anti-tumour effects of BLM occur by formation of a complex with transition metals, such as iron, which in turn catalyses the formation of ROS with the ultimate progression of lipid peroxidation [1, 11, 12]. Increased lung production of O 2 – · has been documented after BLM treatment [9, 33].…”

Section: Discussionmentioning

confidence: 99%

“…The most often cited mechanisms emerging from a plenitude of studies are centred around elevated levels of some cytokines, such as tumour necrosis factor-α [4], stimulation of endothelial cell transforming growth factor-β 1 [5], depletion of NAD and ATP [6], involvement of platelet activating factor [7], and generation of reactive oxygen species (ROS), such as superoxide anion (O 2 – ·) and hydroxyl radicals [8, 9, 10]. It is noteworthy that the generation of free radicals has been proposed to be responsible for both the anti-tumour activity and the cellular toxicity [1, 11, 12]evoked by BLM.…”

Section: Introductionmentioning

confidence: 99%

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

El-Khatib

2002

Chemotherapy

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Background: The present study was undertaken to evaluate whether stimulation or inhibition of nitric oxide (NO) synthesis could affect lung toxicity induced by chronic administration of bleomycin (BLM). L-arginine (ARG) and N^G-nitro-L-arginine methyl ester (L-NAME) were employed as NO precursor and NO synthesis inhibitor, respectively. Methods: BLM was administered intraperitoneally to male Wistar rats at a dose of 15 mg/kg, 3 times a week, for a total period of 4 weeks. ARG (500 mg/kg/day) and L-NAME (100 mg/kg/day) were given in drinking water, the treatments commenced with BLM and continued up to the end of the experiment. Appropriate controls were performed. Results: BLM treatment resulted in a pronounced fall in the average body weight of animals, together with a rise in the lung weight/body weight ratio. In the lung tissue, elevated levels of hydroxyproline (HP) and lipid peroxides (LP) as well as decreased activity of angiotensin converting enzyme (ACE) further evidenced the toxicity. Pulmonary level of NO end products, nitrite and nitrate, tended to rise but did not reach a significant level. Glutathione (GSH) content and GSH-peroxidase activity measured in the lung remained unaltered. In animals given concurrent treatment of BLM and ARG, a remarkable rise in the pulmonary level of nitrite and nitrate was observed. Average body weight was still decreased when compared with the untreated control group, but the decrease was significantly less than that observed in the BLM group. In addition, ARG decreased the extent of BLM-induced elevations of lung HP and LP levels. Meanwhile, ARG failed to significantly affect the BLM-evoked decrease in pulmonary ACE activity and increase in lung weight/body weight ratio. In animals given simultaneous treatment of BLM and L-NAME, noticeable reductions in the pulmonary levels of nitrite/nitrate and GSH were detected. BLM-induced decrease in body weight and increase in lung weight/body weight ratio were accentuated by L-NAME co-treatment. Furthermore, administration of L-NAME led to more profound elevations in lung HP and LP levels, without affecting the decrease in pulmonary ACE activity elicited by BLM. Conclusion: In principle, the present findings indicate that the lung toxicity exerted by chronic administration of BLM is alleviated by ARG, but exacerbated by L-NAME supplementation. This could indicate a possible protective role of NO.

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“…However, at variance with ARDS from other causes, bleomycin-induced ARDS invariably evolves into interstitial lung fibrosis (29,30), generally associated with alveolar wall basement membrane duplication and thickening (31). Oxygen-free derived radicals and intra-cellular ferric ions are thought to be directly involved in the mechanism of bleomycin toxicity onAT2s, since glutathione and iron chelants proved to have a protective role (32). Lately, using a murine model of bleomycin-induced pulmonary fibrosis, Aoshiba et al (33) provided evidence that persistent DNA damage on alveolar epithelial cells was able to induce a senescence-associated secretory phenotype (SASP), characterized by overexpressions of IL-6, TNFa, MMP-2 and MMP-9.…”

Section: Shortness Of Breath 2014; 3 (3): 102-107mentioning

confidence: 99%

Update on acute respiratory distress syndrome�s pathology. Recent insights into in vivo alveolar regeneration

Ficial¹,

Chilosi²

2014

sob

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Direct toxic effect of bleomycin on alveolar type 2 cells

Cited by 15 publications

References 25 publications

The iron chelating cardioprotective prodrug dexrazoxane does not affect the cell growth inhibitory effects of bleomycin

The iron chelating cardioprotective prodrug dexrazoxane does not affect the cell growth inhibitory effects of bleomycin

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

Update on acute respiratory distress syndrome�s pathology. Recent insights into in vivo alveolar regeneration

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