Synthetic liposomes are protective from bleomycin-induced lung toxicity

Gwinn, William M.; Kapita, Mayanga; Wang, Ping M.; Cesta, Mark F.; Martin, William J.

doi:10.1152/ajplung.00149.2010

Cited by 10 publications

(5 citation statements)

References 40 publications

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“…All animal studies were approved by the CNIO IACUC, by the ethics and animal welfare committee of the the Instituto de Salud Carlos III (Madrid, Spain) and by the Comunidad de Madrid (Madrid, Spain), in accordance with National and European regulations. In the case of the MHV68-induced lung fibrosis mouse model, the protocol was approved by the Emory University Institutional Animal Care and Use Committee and in accordance with established guidelines and policies at Emory University School of Medicine (pro-prevented fibrosis in several models (69,70), including bleomycininduced lung fibrosis (11,63,71,72). Nintedanib, the first-line treatment for IPF, is a potent inhibitor of several growth factor receptors, including the macrophage-survival cytokine M-CSF-R. Nintedanib reduces circulating M-CSF and skin AAMs in Fra-2 Tg mice and ameliorates skin and lung fibrosis (46).…”

Section: Discussionmentioning

confidence: 99%

Fra-2–expressing macrophages promote lung fibrosis

Ucero

Bakiri

Roediger

et al. 2019

Journal of Clinical Investigation

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at. tocol YER-2002245-031416GN). The protocol was also carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals (National Academies Press, 2011). The project design to obtain human samples was approved by the ethical committee of the Instituto de Salud Carlos III (Madrid, Spain). In addition, samples and/or data from patients included in this study were provided by the Biobanco i+12 in the Hospital 12 de Octubre integrated in the Spanish Hospital Biobanks Network (RetBioH; www. redbiobancos.es) following standard operation procedures, with appropriate approval of the Ethical and Scientific Commitees, Madrid Spain. Paraffin-embedded tissue sections and OCT-embedded fresh tissue from 11 pulmonary fibrosis patients and 3 controls without any lung pathology were obtained. All patients provided informed consent.

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Section: Discussionmentioning

confidence: 99%

Fra-2–expressing macrophages promote lung fibrosis

Ucero

Bakiri

Roediger

et al. 2019

Journal of Clinical Investigation

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“…Pulmonary fibrosis severity was quantified by calculating the MT staining pulmonary collagen-positive area (blue) using Image-Pro Plus 6.0 software (Media Cybernetics, Silver Spring, MD, United States). The lung sections were graded by two independent pathologists (Yuan Miao, and Qianze Dong, Associated Professors of Pathology, China Medical University) to determine fibrosis severity using the scale shown below, as described in previous studies ( Gwinn et al, 2011 ). The pathologist determined (1) a severity score for fibrosis and chronic inflammation and (2) the distribution (% area affected) of fibrosis or chronic inflammation in the lung section.…”

Section: Methodsmentioning

confidence: 99%

GHK Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice by Suppressing TGFβ1/Smad-Mediated Epithelial-to-Mesenchymal Transition

Zhou¹,

Wang²,

Wang³

et al. 2017

Front. Pharmacol.

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Objective: Idiopathic pulmonary fibrosis is an irreversible and progressive fibrotic lung disease that leads to declines in pulmonary function and, eventually, respiratory failure and has no effective treatment. Gly-His-Lys (GHK) is a tripeptide involved in the processes of tissue regeneration and wound healing and has significant inhibitory effects on transforming growth factor (TGF)-β1 secretion. The effect of GHK on fibrogenesis in pulmonary fibrosis and the exact underlying mechanism have not been studied previously. Thus, this study investigated the effects of GHK on bleomycin (BLM)-induced fibrosis and identified the pathway that is potentially responsible for these effects.Methods: Intratracheal injections of 3 mg/kg BLM were administered to induce pulmonary fibrosis in C57BL/6 mice. GHK was administered intraperitoneally at doses of 2.6, 26, and 260 μg/ml/day every other day from the 4th to the 21st day after BLM instillation. Three weeks after BLM instillation, pulmonary injury and pulmonary fibrosis was evaluated by the hematoxylin-eosin (HE) and Masson’s trichrome (MT) staining. Chronic inflammation index was used for the histological assessments by two pathologists blindly to each other. Tumor necrosis factor (TNF)-α and IL-6 levels in BALF and myeloperoxidase (MPO) activity in lung extracts were measured. For the pulmonary fibrosis evaluation, the fibrosis index calculated based on MT staining, collagen deposition and active TGF-β1 expression detected by ELISA, and the expression of TGF-β1, α-smooth muscle actin (SMA), fibronectin, MMP-9, and TIMP-1 by western blotting. The epithelial mesenchymal transition index, E-cadherin, and vimentin was also detected by western blot. The statistical analysis was performed by one-way ANOVA and the comparison between different groups were performed.Results: Treatment with GHK at all three doses reduced inflammatory cell infiltration and interstitial thickness and attenuated BLM-induced pulmonary fibrosis in mice. GHK treatment significantly improved collagen deposition, and MMP-9/TIMP-1 imbalances in lung tissue and also reduced TNF-α, IL-6 expression in bronchoalveolar lavage fluid (BALF) and MPO in lung extracts. Furthermore, GHK reversed BLM-induced increases in TGF-β1, p-Smad2, p-Smad-3 and insulin-like growth factor-1 (IGF-1) expression.Conclusion: GHK inhibits BLM-induced fibrosis progression, the inflammatory response and EMT via the TGF-β1/Smad 2/3 and IGF-1 pathway. Thus, GHK may be a potential treatment for pulmonary fibrosis.

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“…Nowadays, various types of drug delivery systems have been developed for passive or active targeting of cancer cells. There have been many attempts to develop new drug delivery systems for BLM, including fusogenic DOPE-liposomes of BLM for enhancing the efficacy of BLM in mouse model of breast cancer [4], synthetic liposomes for airway-delivery of BLM to reduce the lung toxicity associated with BLM in a mouse model [5], liposomal formulation of BLM for enhancing its antitumour activity against Lewis lung cancer [6] and chitosan based polymeric vesicles for studying pharmacokinetics of biodistribution of BLM in male Balb/c mice [7]. Although, in some cases, there have been promising results, but most of them are suffering from poor therapeutic efficacy.…”

Section: Introductionmentioning

confidence: 99%

Folic acid conjugated nanoliposomes as promising carriers for targeted delivery of bleomycin

Chiani

Norouzian

Shokrgozar

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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Targeted drug delivery has received considerable attention due to its key role in improving therapeutic efficacy and reducing the side effects of anticancer drugs. Bleomycin (BLM) is an anticancer antibiotic with short half-life, low therapeutic and high side effects that limit its clinical applications. This study aims to evaluate the anticancer potential of folate-targeted liposomal bleomycin (FL-BLM) and its free-folate form (L-BLM) on two different cancer cell lines including human cervix carcinoma HeLa, and human breast carcinoma MCF-7 cells. Furthermore, the effect of FL-BLM in induction of apoptosis and cell cycle arrest was studied by flow cytometry. FL-BLM was prepared by thin film hydration method and folic acid was conjugated to nanoliposomes by post insertion technique. Anticancer activity was evaluated by MTT assay. The cytotoxicity of FL-BLM against HeLa cells was significantly increased compared to L-BLM and conventional BLM. Flow cytometry and annexin-V analysis indicated that FL-BLM effectively induced apoptosis and cell-cycle arrest in HeLa cells especially at G2/M phase. In addition, the uptake of FL-BLM by Hela cells was significantly increased as compared to the MCF-7 cells. Overall, our findings indicated that FL-BLM may be promising formulation for targeted drug delivery to folate receptor-positive tumour cells.

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Synthetic liposomes are protective from bleomycin-induced lung toxicity

Abstract: Gwinn WM, Kapita MC, Wang PM, Cesta MF, Martin WJ 2nd. Synthetic liposomes are protective from bleomycin-induced lung toxicity.

Cited by 10 publications

References 40 publications

Fra-2–expressing macrophages promote lung fibrosis

Fra-2–expressing macrophages promote lung fibrosis

GHK Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice by Suppressing TGFβ1/Smad-Mediated Epithelial-to-Mesenchymal Transition

Folic acid conjugated nanoliposomes as promising carriers for targeted delivery of bleomycin

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