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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bleomycin is a commonly used antineoplastic agent which produces dose- and time-dependent pneumonitis and fibrosis in humans. The mechanism of bleomycin-induced lung injury is uncertain. However, current data shows that bleomycin can generate reactive oxygen species such as superoxide and hydroxyl radicals. We therefore investigated whether intraperitoneal (i.p.) injection of endotoxin, a protectant for hyperoxia, could modulate the biochemical and morphological estimates of bleomycin-induced lung fibrosis in rats. However, pretreatment with multiple i.p. injections of endotoxin, combined with intratracheal bleomycin instillation, resulted in increased lung collagen content compared to bleomycin treatment alone and controls. Furthermore, morphological estimates of the severity of lung lesions present in the endotoxin-bleomycin treatment group were increased when compared with saline and endotoxin control lung lesions. These data indicate, in the current study design, that endotoxin did not reduce, but instead increased the severity of bleomycin-induced pulmonary fibrosis in rats. The mechanism for this increase in fibrosis may be the result of pre-existing endotoxin-induced cell injury.
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PMID:The effect of endotoxin on bleomycin-induced lung fibrosis in the rat. 241 66

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.
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PMID:Bleomycin-induced pulmonary endothelial cell injury: evidence for the role of iron-catalyzed toxic oxygen-derived species. 243 23

Bleomycin 0.4, 0.6, 1.0 or 3.5 mg/kg body weight was administered via the trachea in rats. After various time intervals some of the animals were exposed to 50% oxygen for either 4 or 24 h. The rats were then sacrificed at different times. Control rats remained untreated or received physiological saline. Lung histology was studied by light microscopy. In a number of rats the lung content of hydroxyproline was determined. Mild reactions, namely increases in pneumocytes type II and macrophages, oedema and prefibrotic alterations were observed after the instillation of bleomycin. The reactions were comparable to those observed after additional hyperoxia alone. Lung hydroxyproline concentration was not increased after bleomycin plus oxygen as compared with bleomycin alone. We conclude that no added toxicity is caused by 50% oxygen supplied for 4 or 24 h subsequent to doses of bleomycin that lead to mild pulmonary abnormalities in the absence of hyperoxia.
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PMID:Absence of an additional fibrotic response caused by oxygen in the lungs of rats after the intratracheal administration of bleomycin. 246 Dec 15

Bleomycin is a primary fibrogenic agent which increases collagen content in a fibroblast system by a direct effect on fibroblasts. A mechanism for the increase in collagen content is an increase in the rate of collagen biosynthesis. This implies alteration of either collagen transcription or translation. Hyperoxia depresses collagen biosynthesis without changing collagen content. This implies that hyperoxia also depresses collagen degradation. The addition of phagocytes (macrophages) to hyperoxically exposed cells increases both collagen content and the rate of collagen biosynthesis. Hyperoxia is therefore a secondary fibrogenic agent. This suggests that mediators released from phagocytes alter collagen transcription or translation.
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PMID:Some implications of augmented collagen levels with bleomycin exposure or hyperoxic exposure of lung fibroblasts: fibrosis as altered phenotypic expression. 620 69

Inhalation of high concentration of oxygen produces a lung injury in men and experimental animals. In our previous experiment we have found suppression of cough reflex in healthy guinea pigs after an exposure to 100% O2 for 60 hours. This study was designed to find the effect of hyperoxia on cough reflex in guinea pigs with lungs damaged by bleomycin. We used 48 animals (300-400 g) in two separated experiments. 32 of them were intratracheally injected with 1.5 mg bleomycin (Bleocin, Nippon Kayaku Co., Ltd., Tokyo, Japan) for induction of lung damage according to the method described by Parizada et al (20). 16 animals were given saline, only (control). Animals of experimental group were divided into two subgroups according to the lapse of time from bleomycin application. 13 days after bleomycin application animals of the 1st subgroup (16) were exposed to 100% O2 (8) or to room air (8) for 48 h. Similarly, 20 days after bleomycin application guinea pigs of the 2nd subgroup (16) were exposed to 100% O2 (8) or air (8), respectively. Cough was provoked in conscious animals placed in bodyplethysmograph box by inhalation of citric acid aerosol (0.3 mol/L) before, then 13 or 20 days after bleomycin application, and finally at the end of 48-h exposition to 100% O2 (air). The number of coughs was counted from airflow trace recorded by pneumotachograph. Cough was also induced by mechanical stimulation of laryngopharyngeal (LPh) and tracheobronchial (TBr) region in anaesthetized animals (Urethane, 1.1 g/kg, i.p.) just after the end of oxygen exposition and was evaluated from the interpleural pressure record. The results have shown a tendency to inhibition of citric acid cough reflex in animals 13 days treated with bleomycin and exposed to 100% O2, and significant decrease in citric acid induced cough in animals 20 days treated with bleomycin and exposed to 100% O2. Significant changes were present in cough intensity induced by mechanical stimulation of TBr region of the guinea pigs airway treated with bleomycin and exposed to oxygen, too. (Tab. 1, Fig. 3, Ref: 29.)
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PMID:The influence of hyperoxia on cough reflex intensity in guinea pigs treated with bleomycin. 1525 38