Bleomycin‐induced pulmonary toxicity and treatment with infliximab: A case report

Ge, Victor; Banakh, Iouri; Tiruvoipati, Ravindranath; Haji, Kavi

doi:10.1002/ccr3.1790

Cited by 15 publications

(12 citation statements)

References 21 publications

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“…Bleomycin is a successful chemotherapeutic drug against a variety of malignancies, however the mortality of bleomycin-induced pulmonary toxicity was noticed, and bleomycin administration led to a decrease in the antioxidant enzymes activity and increase in lipid peroxidation in lung tissue (16). Melatonin improved pulmonary function, and regulated the senescence-associated secretory phenotype (SASP) in fibroblast cells of human fetal lung.…”

Section: Discussionmentioning

confidence: 99%

The Possible Protective Effect of Melatonin and Coenzyme Q10 on Lung Injury Induced by Bleomycin in Adult Male Albino Rats

Elkerdasy

Elshazly

Baioumy

et al. 2021

The Egyptian Journal of Hospital Medicine

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Background: bleomycin-induced lung toxicity and oxidative damage by decreasing the deactivating enzyme, genetic vulnerability, and released cytokines of inflammation. Melatonin has a free radical detoxifying effect, coenzyme Q10 has a strong antioxidant effect. Aim of the study: this study aimed to evaluate the possible protective role of melatonin and coenzyme Q10 in bleomycin-induced lung injury in Albino rats. Material and Methods: forty male Albino rats were categorized into five groups; group I (control group), group II (bleomycin group): rats were given a single dose of bleomycin intra-tracheal for inducing lung injury, group III (melatonin group): rats were given melatonin for three weeks after intratracheal installation of bleomycin, group IV (coenzymeQ10 group): rats were given coenzymeQ10 for three weeks after intratracheal installation of bleomycin and group V (combined melatonin and Co Q10 group): rats were given a combination of melatonin and coenzyme Q10for three weeks after induction of bleomycin lung toxicity. Lung tissues were prepared for biochemical, histological and immunohistochemical studies. Results: bleomycin produced a significant increase in the level of malondialdehyde and a significant reduction in glutathione peroxidase activity in lung tissues with loss of normal histological lung architecture, significant elevation in main area percent of collagen fibers deposition and caspase-3 immuno positive expression. In group III melatonin enhanced a significant improvement in the biochemical changes, moderate prevention of histopathological changes in lung tissue with a significant reduction in main area percent of collagen fibers deposition and caspase-3 immuno positive expression. While, in group IV co enzyme Q10 enhanced non significant improvement in the biochemical changes, mild prevention of histopathological changes and non-significant reduction in main area percent of collagen fibers deposition and caspase-3 immuno positive expression. Using a combination of both drugs in group V enhanced a significant improvement in the biochemical changes and almost preservation of normal histological architecture of the lung tissue. Conclusion: administration of both melatonin and coenzyme Q10 produced almost a complete recovery of bleomycin induced lung injury.

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Section: Discussionmentioning

confidence: 99%

The Possible Protective Effect of Melatonin and Coenzyme Q10 on Lung Injury Induced by Bleomycin in Adult Male Albino Rats

Elkerdasy

Elshazly

Baioumy

et al. 2021

The Egyptian Journal of Hospital Medicine

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“…2 Bleomycin interferes with the growth and proliferation of cancer cells and helps to inhibit cancer. 2 , 3 Also, bleomycin is useful in treating cancer-induced pleural effusions and growth. However, like most antineoplastic agents’ bleomycin can also affect normal cells leading to other unwanted or undesirable side effects.…”

Section: Introductionmentioning

confidence: 99%

“…Bleomycin use may cause decreased appetite, vomiting, nausea, skin darkening, hair loss, but most importantly it can induce severe pulmonary toxicity in cancer patients. 3 , 4 The transcriptome profiles of the immortalized lymphoblastoid cells (TK6 cells) in vitro after treatment with different drugs or chemicals were obtained to decipher their genotoxicity. 5 Unlike most cancer cells which are routinely used for basic or translational research, the TK6 cells do not carry many genetic changes or mutations.…”

Section: Introductionmentioning

confidence: 99%

Defining the role of the antineoplastic drug bleomycin based on toxicogenomic-DNA damage inducing (TGx-DDI) genomic biomarkers data: A meta-analysis using next-generation knowledge discovery method

et al. 2023

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Objectives: Accurately identifying the cellular, biomolecular, and toxicological functions of anticancer drugs help to decipher the potential risk of genotoxicity and other side effects. Here, we examined bleomycin for cellular, molecular and toxicological mechanisms using next-generation knowledge discovery (NGKD) tools. Methods: This study was conducted at the Faculty of Applied Medical Sciences, King Abdulaziz University (KAU), Jeddah, Saudi Arabia in October 2022. We first analyzed the raw Toxicogenomic and DNA damage-inducing (TGx-DDI) gene expression data from Gene Expression Omnibus (GEO) (GSE196373) of TK6 cells treated with 10 µM bleomycin and TK6 cells treated with DMSO for four hours using the GEO2R tool based on the Linear Models for Microarray Analysis (limma) R packages to derive the differentially expressed genes (DEGs). Then, iPathwayGuide was used to determine differentially regulated signaling pathways, biological processes, cellular, molecular functions and upstream regulators (genes and miRNAs). Results: Bleomycin differently regulates the p53 pathway, transcriptional dysregulation in cancer, FOXO pathway, viral carcinogenesis, and cancer pathways. The biological processes such as p53 class mediator signaling, intrinsic apoptotic signaling, DNA damage response, and DNA damage-induced intrinsic apoptotic signaling and molecular functions like ubiquitin protein transferase and p53 binding were differentially regulated by bleomycin. iPathwayGuide analysis showed that the p53 and its regulatory gene and microRNA networks induced by bleomycin. Conclusion: Analysis of TGx-DDI data of bleomycin using NGKD tools provided information about toxicogenomics and other mechanisms. Integration of all “omics” based approaches is crucial for the development of translatable biomarkers for evaluating anticancer drugs for safety and efficacy. doi: https://doi.org/10.12669/pjms.39.2.7321 How to cite this: Pushparaj PN, Rasool M, Naseer MI, Gauthaman K. Defining the role of the antineoplastic drug bleomycin based on toxicogenomic-DNA damage inducing (TGx-DDI) genomic biomarkers data: A meta-analysis using next-generation knowledge discovery method. Pak J Med Sci. 2023;39(2):---------. doi: https://doi.org/10.12669/pjms.39.2.7321 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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“…Pulmonary toxicity is a frequent side effect of some medications, such as bleomycin (BLM), amiodarone, and alkylating agents. [ 1,2 ] BLM is a chemotherapy agent with the potential for producing pulmonary toxicity. BLM‐induced pulmonary injury and pneumonitis have been well described as a complication of such therapy.…”

Section: Introductionmentioning

confidence: 99%

“…BLM‐induced pulmonary injury and pneumonitis have been well described as a complication of such therapy. [ 1 ] Additionally, pulmonary fibrosis can develop in patients undergoing BLM treatment. BLM complexes with iron lead to the production of free radicals and decrease in the levels of antioxidant enzymes, resulting in oxidative damage of cell membranes and DNA and cell death in pulmonary epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin attenuates pulmonary fibrosis in mice and human lung fibroblasts, by the regulation of myofibroblast differentiation and apoptosis

Yıldırım

Kayalar

Atahan

et al. 2022

J Biochem & Molecular Tox

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Statins have anti‐inflammatory and antifibrotic effects in addition to cholesterol‐lowering effect. We aimed to investigate the effect of atorvastatin (ATR) in fibrotic mouse lung and human lung fibroblasts (MRC5s). Pulmonary fibrosis was induced by a single dose of bleomycin by intratracheal instillation in adult mice. ATR was administered (20 mg/kg ip) to mice with healthy and pulmonary fibrosis for 10 days from Day 7 of the experiment. Mice were dissected on the 21st day. The levels of alpha‐smooth muscle actin (α‐SMA), pSMAD2/3, LOXL2, and p‐Src were determined by Western blot analysis in the lungs. Furthermore, a group of MRC5 was differentiated into myofibroblasts by transforming growth factor‐beta (TGF‐β). Another group of MRC5s was treated with 10 µM ATR at 24 h after TGF‐β stimulation. Cells were collected at 0, 24, 48, and 72 h. The effects of ATR on myofibroblast differentiation, apoptosis, and TGF‐β and Wnt/β‐catenin signaling activations were examined by Western blot analysis and flow cytometry in MRC5s. ATR attenuated pulmonary fibrosis by regulating myofibroblast differentiation and interstitial accumulation of collagen, by acting on LOXL2, p‐Src, and pSMAD2/3 in mice lungs. Additionally, it blocked myofibroblast differentiation via reduced TGF‐β and Wnt/β‐catenin signaling and decreased α‐SMA in MRC5s stimulated with TGF‐β. Moreover, ATR caused myofibroblast apoptosis via caspase‐3 activation. ATR treatment attenuates pulmonary fibrosis in mice treated with bleomycin. It also inhibits fibroblast/myofibroblast activation, by both reducing myofibroblasts differentiation and inducing myofibroblast apoptosis.

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Bleomycin‐induced pulmonary toxicity and treatment with infliximab: A case report

Cited by 15 publications

References 21 publications

The Possible Protective Effect of Melatonin and Coenzyme Q10 on Lung Injury Induced by Bleomycin in Adult Male Albino Rats

The Possible Protective Effect of Melatonin and Coenzyme Q10 on Lung Injury Induced by Bleomycin in Adult Male Albino Rats

Defining the role of the antineoplastic drug bleomycin based on toxicogenomic-DNA damage inducing (TGx-DDI) genomic biomarkers data: A meta-analysis using next-generation knowledge discovery method

Atorvastatin attenuates pulmonary fibrosis in mice and human lung fibroblasts, by the regulation of myofibroblast differentiation and apoptosis

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