Abstract:
:Bleomycin (BLM) is an effective curative option in the management of several malignancies including pleural effusions; but pulmonary toxicity, comprising of pneumonitis and fibrosis, poses challenge in its use as a front-line chemotherapeutic. Although Amifostine has been found to protect lungs from the toxic effects of radiation and BLM, its application is limited due to associated toxicity and unfavorable route of administration. Therefore, there is a need for selective, potent, and safe anti-fibrotic drugs. The current study was undertaken to assess the protective effects of DRDE-30, an analog of Amifostine, on BLM-induced lung injury in C57BL/6 mice. Whole body micro- computed tomography (CT) was used to non-invasively observe tissue damage, while broncheo-alveolar lavage fluid (BALF) and lung tissues were assessed for oxidative damage, inflammation and fibrosis. Changes in the lung density revealed by micro-CT suggested protection against BLM-induced lung injury by DRDE-30, which correlated well with changes in lung morphology and histopathology. DRDE-30 significantly blunted BLM-induced oxidative stress, inflammation and fibrosis in the lungs evidenced by reduced oxidative damage, endothelial barrier dysfunction, Myeloperoxidase (MPO) activity, pro-inflammatory cytokine release and protection of tissue architecture, that could be linked to enhanced anti-oxidant defense system and suppression of redox-sensitive pro-inflammatory signaling cascades. DRDE-30 decreased the BLM-induced augmentation in BALF TGF-β and lung hydroxyproline levels, as well as reduced the expression of the mesenchymal marker α-smooth muscle actin (α-SMA), suggesting the suppression of epithelial to mesenchymal transition (EMT) as one of its anti-fibrotic effects. The results demonstrate that the Amifostine analog, DRDE-30, ameliorates the oxidative injury and lung fibrosis induced by BLM and strengthen its potential use as an adjuvant in alleviating the side effects of BLM.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Arora A,Bhuria V,Hazari PP,Pathak U,Mathur S,Roy BG,Sandhir R,Soni R,Dwarakanath BS,Bhatt ANdoi
10.3389/fphar.2018.00394subject
Has Abstractpub_date
2018-04-24 00:00:00pages
394issn
1663-9812journal_volume
9pub_type
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journal_title:Frontiers in pharmacology
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abstract::Nanomaterials with localized surface plasmon resonance (LSPR) have exquisite optical properties, which allow a wide range of applications. Non-stoichiometric copper sulfides with active LSPR have drawn great attention, because its LSPR peak falls in the NIR region that is suitable for deep bioimaging and photothermal ...
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abstract::Kappa receptor activation by dynorphins contributes to the anxiogenic, dysphoric, and cognitive disrupting effects of repeated stress, suggesting that kappa receptor antagonists might have therapeutic utility in the treatment of stress disorders. Three classes of kappa antagonists have been distinguished: non-selectiv...
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abstract::Hypertension is a prevalent, complex, and polygenic cardiovascular disease, which is associated with increased mortality and morbidity. Across the world, traditional Chinese medicine (TCM) constituted by herbal medicine and non-pharmacological therapies is used to assist blood pressure management. Though widely accept...
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abstract::Cystic Fibrosis (CF) is a recessive genetic disease due to mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene encoding the CFTR chloride channel. The ion transport abnormalities related to CFTR mutation generate a dehydrated airway surface liquid (ASL) layer, which is responsible for an a...
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abstract:Background:5α-reductase type 2 deficiency (5αRD) is an autosomal recessive hereditary disease of the group of 46, XY disorders of sex development (DSD). Objective:To study the growth pattern in Chinese pediatric patients with 5αRD. Subjects:Data were obtained from 141 patients with 5αRD (age: 0-16 years old) who visi...
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doi:10.3389/fphar.2019.00108
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pub_type: 杂志文章
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2015.00177
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pub_type: 杂志文章
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journal_title:Frontiers in pharmacology
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
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doi:10.3389/fphar.2019.00861
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