Bleomycin increases superoxide production in the most active alveolar macrophage subpopulation

Zeidler, Robert; Yarbro, John W.; Conley, Nick

doi:10.1016/0192-0561(87)90040-3

Cited by 5 publications

(2 citation statements)

References 14 publications

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“…Bleomycin is known to enhance free radical generation and lipid peroxidation in cells [56] – [58] , that may account for its radiomimetic actions. On the other hand, AA, being an unsaturated fatty acid, is known to be more susceptible for peroxidation [2] , [59] .…”

Section: Resultsmentioning

confidence: 99%

Effect of Polyunsaturated Fatty Acids and Their Metabolites on Bleomycin-Induced Cytotoxic Action on Human Neuroblastoma Cells In Vitro

Polavarapu¹,

Mani²,

Gundala³

et al. 2014

PLoS ONE

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In the present study, we noted that bleomycin induced growth inhibitory action was augmented by all the polyunsaturated fatty acids (PUFAs) tested on human neuroblastoma IMR-32 (0.5×104 cells/100 µl of IMR) cells (EPA> DHA> ALA = GLA = AA> DGLA = LA: ∼60, 40, 30, 10–20% respectively) at the maximum doses used. Of all the prostaglandins (PGE1, PGE2, PGF2α, and PGI2) and leukotrienes (LTD4 and LTE4) tested; PGE1, PGE2 and LTD4 inhibited the growth of IMR-32 cells to a significant degree at the highest doses used. Lipoxin A4 (LXA4), 19,20-dihydroxydocosapentaenoate (19, 20 DiHDPA) and 10(S),17(S)-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoic acid (protectin: 10(S),17(S)DiHDoHE), metabolites of DHA, significantly inhibited the growth of IMR-32 cells. Pre-treatment with AA, GLA, DGLA and EPA and simultaneous treatment with all PUFAs used in the study augmented growth inhibitory action of bleomycin. Surprisingly, both indomethacin and nordihydroguaiaretic acid (NDGA) at 60 and 20 µg/ml respectively enhanced the growth of IMR-32 cells even in the presence of bleomycin. AA enhanced oxidant stress in IMR-32 cells as evidenced by an increase in lipid peroxides, superoxide dismutase levels and glutathione peroxidase activity. These results suggest that PUFAs suppress growth of human neuroblastoma cells, augment growth inhibitory action of bleomycin by enhancing formation of lipid peroxides and altering the status of anti-oxidants and, in all probability, increase the formation of lipoxins, resolvins and protectins from their respective precursors that possess growth inhibitory actions.

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Section: Resultsmentioning

confidence: 99%

Effect of Polyunsaturated Fatty Acids and Their Metabolites on Bleomycin-Induced Cytotoxic Action on Human Neuroblastoma Cells In Vitro

Polavarapu¹,

Mani²,

Gundala³

et al. 2014

PLoS ONE

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“…Moreover, it has been previously demonstrated that primary human dermal fibroblasts and other fibroblasts release increasing amounts of adenosine under stimulated conditions, such as following exposure to H 2 O 2 , stimulated polymorphonuclear neutrophils, or methotrexate treatment (14–17). Bleomycin, a widely used fibrosing agent, promotes the generation of reactive oxygen species and resultant induction of oxidative stress (18–22), and antioxidants attenuate bleomycin‐induced fibrosis, at least in the lung (23). Cellular release of adenosine is known to be increased under conditions of oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Adenosine A_2A receptors in diffuse dermal fibrosis: Pathogenic role in human dermal fibroblasts and in a murine model of scleroderma

Chan

Fernández

Merchant

et al. 2006

Arthritis & Rheumatism

119

120

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.Conclusion. These results demonstrate that adenosine A 2A receptors play an active role in the pathogenesis of dermal fibrosis and suggest a novel therapeutic target in the treatment and prevention of dermal fibrosis in diseases such as scleroderma.Adenosine, a product of ATP catabolism, is released from cells and tissues under conditions of stress or hypoxia and is a potent endogenous physiologic and pharmacologic mediator. Adenosine regulates cellular and organ function via interaction with a family of 4 G protein-coupled receptors, A 1 , A 2A , A 2B , and A 3.

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Effect of stabling on bronchoalveolar cells obtained from normal and COPD horses

Tremblay

Ferland

Lapointe

et al. 1993

Equine Veterinary Journal

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Summary Bronchoalveolar lavages (BAL) were performed before and after 3 weeks of housing in 5 horses suffering from COPD and 5 normal horses. In the two groups, the total number of cells recovered remained unchanged after stabling. The most common cell populations in BAL fluid of control animals were alveolar macrophages (46.4%) and lymphocytes (44.9%). The percentage of neutrophils increased after stabling from 8.7% to 27.6%. In COPD horses, lymphocytes predominated (40.7%) in animals at pasture with neutrophils increasing from 29.4% to 71.6% after stabling. After fractionation by Percoll density gradient, alveolar macrophages and neutrophils from normal and COPD horses had a similar density distribution. After stabling, these cells from normal horses were increased in the low density layers, while those from COPD horses were predominantly in the hyperdense layers. Therefore, BAL cells obtained from COPD animals at pasture and after stabling differ from those of control horses in the same environment, not only in their populations but also in their buoyant densities. These differences could be related to different states of cellular activation and perhaps be responsible for disease activity in the COPD horses.

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Bleomycin increases superoxide production in the most active alveolar macrophage subpopulation

Cited by 5 publications

References 14 publications

Effect of Polyunsaturated Fatty Acids and Their Metabolites on Bleomycin-Induced Cytotoxic Action on Human Neuroblastoma Cells In Vitro

Effect of Polyunsaturated Fatty Acids and Their Metabolites on Bleomycin-Induced Cytotoxic Action on Human Neuroblastoma Cells In Vitro

Adenosine A_2A receptors in diffuse dermal fibrosis: Pathogenic role in human dermal fibroblasts and in a murine model of scleroderma

Effect of stabling on bronchoalveolar cells obtained from normal and COPD horses

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Bleomycin increases superoxide production in the most active alveolar macrophage subpopulation

Cited by 5 publications

References 14 publications

Effect of Polyunsaturated Fatty Acids and Their Metabolites on Bleomycin-Induced Cytotoxic Action on Human Neuroblastoma Cells In Vitro

Effect of Polyunsaturated Fatty Acids and Their Metabolites on Bleomycin-Induced Cytotoxic Action on Human Neuroblastoma Cells In Vitro

Adenosine A2A receptors in diffuse dermal fibrosis: Pathogenic role in human dermal fibroblasts and in a murine model of scleroderma

Effect of stabling on bronchoalveolar cells obtained from normal and COPD horses

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Adenosine A_2A receptors in diffuse dermal fibrosis: Pathogenic role in human dermal fibroblasts and in a murine model of scleroderma