The Role of Hypertension and Renin-angiotensin-aldosterone System Inhibitors in Bleomycin-induced Lung Injury

Hara, Ryujiro; Onizuka, Makoto; Shiraiwa, Sawako; Harada, Kaito; Aoyama, Yasuyuki; Ogiya, Daisuke; Toyosaki, Masako; Suzuki, Rikio; Machida, Sinichiro; Ohmachi, Ken; Ogawa, Yoshiaki; Kawada, Hiroshi; Watanabe, Shigeki; Miyajima, Akira; Masuda, Ryosuke; Iwazaki, Masayuki; Mikami, Mikio; Kitahara, Takashi; Mochizuki, Hiroyuki; Ando, Kiyoshi

doi:10.1016/j.clml.2020.10.004

Cited by 6 publications

(2 citation statements)

References 52 publications

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“…It has been clinically proven that BLM is used mainly as a chemotherapeutic due to lack of myelosuppression and immunosuppression [1]. The glycopeptide antibiotic is administered in malignancies, testicular cancer, Hodgkin's lymphoma, but subsequently induces dose-dependent interstitial lung toxicity and lung tissue inflammation, which limits its clinical use [1,2]. BLM exerts its cytotoxic effect in vivo by cleaving the DNA structure in a biochemical process dependent on the presence of two cofactors-the molecular oxygen presence and the presence of metallic Fe (II) ion.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Protein Oxidation and Oxidative Stress Modulation by Lemna minor L. in Progressive Bleomycin-Induced Idiopathic Pulmonary Fibrosis

et al. 2022

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Bleomycin (BLM) administration is associated with multifunctional proteins inflammations and induction of idiopathic pulmonary fibrosis (IPF). Lemna minor L. extract, a free-floating monocot macrophyte possesses antioxidant and anti-inflammatory potential. The aim of the study was to examine the protective effect of L. minor extract on lung protein oxidation and oxidative stress modulation by BLM-induced pulmonary fibrosis in Balb/c mice. For this purpose, the protein carbonyl content, advanced glycation end product, nitroxide protein oxidation (5-MSL), and lipid peroxidation (as MDA and ROS), in lung cells were examined. The histological examinations, collagen deposition, and quantitative measurements of IL-1β, IL-6, and TNF in lung tissues and blood were investigated. Intraperitoneal, BLM administration (0.069 U/mL; 0.29 U/kg b.w.) for 33 days, caused IPF induction in Balb/c mice. Pulmonary combining therapy was administered with L. minor at dose 120 mg/mL (0.187 mg/kg b.w.). L. minor histologically ameliorated BLM induced IPF in lung tissues. L. minor significantly modulated (p < 0.05) BLM-alterations induced in lung hydroxyproline, carbonylated proteins, 5-MSL-protein oxidation. Oxidative stress decreased levels in antioxidant enzymatic and non-enzymatic systems in the lung were significantly regulated (p < 0.05) by L. minor. L. minor decreased the IL-1β, IL-6, and TNF-α expression in lung tissues and plasma. The L. minor improves the preventive effect/defense response in specific pulmonary protein oxidation, lipid peroxidation, ROS identifications, and cytokine modulation by BLM-induced chronic inflammations, and could be a good antioxidant, anti-inflammatory, and anti-fibrotic alternative or IPF prevention involved in their pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Pulmonary Protein Oxidation and Oxidative Stress Modulation by Lemna minor L. in Progressive Bleomycin-Induced Idiopathic Pulmonary Fibrosis

et al. 2022

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“…In addition to the ECM remodeling effects noted above, elimination of plasma ALD secretion may provide another explanation for the protective effects of adrenalectomy in the bleomycin model. Previous research has demonstrated that RAAS antagonists are protective against bleomycin induced lung injury in patients receiving bleomycin chemotherapy [38] and angiotensin-converting enzyme inhibitors have been shown to be effective in the mitigation of fibrosis caused by the SARS-CoV-2 virus [39]. While our results are promising, further research is needed to understand the interactions between RAAS activity and pulmonary fibrosis.…”

Section: As Expected Airway Inflammation Which Has Been Associated Wi...mentioning

confidence: 69%

The Effect of Adrenalectomy on Bleomycin-Induced Pulmonary Fibrosis in Mice

McGovern,

Perry,

Ghincea

et al. 2024

Preprint

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Progressive lung fibrosis is often fatal and has limited treatment options. Though the mechanisms are poorly understood, fibrosis is increasingly linked with catecholamines such as adrenaline (AD) and noradrenaline (NA), and hormones such as aldosterone (ALD). The essential functions of adrenal glands include the production of catecholamines and numerous hormones, but the contribution of adrenal glands to lung fibrosis remains less well studied. Here, we characterized the impact of surgical adrenal ablation in the bleomycin model of lung fibrosis. Wild type mice underwent surgical adrenalectomy or sham surgery followed by bleomycin administration. We found that the bleomycin induced collagen over deposition in the lung was not affected by adrenalectomy. However, histologic indices of lung remodeling were ameliorated by adrenalectomy. These findings were accompanied by a decrease in bronchoalveolar lavage (BAL) cell count along with concomitant reductions in alpha smooth muscle actin (⍺SMA) and fibronectin. Surgical adrenalectomy completely abrogated AD detection in all compartments, but only reduced NA in the BAL of uninjured mice. Systemic ALD levels were reduced after adrenalectomy. Taken together, these results support the presence of pulmonary-adrenal axis in lung fibrosis and suggest that adrenalectomy is protective in this disease. Further investigation will be needed to better understand this observation and aid in the development of novel therapeutic strategies.

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Mechanisms of Bleomycin-induced Lung Fibrosis: A Review of Therapeutic Targets and Approaches

Mohammed,

Al-Saedi,

Mohammed

et al. 2024

Cell Biochem Biophys

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The Role of Hypertension and Renin-angiotensin-aldosterone System Inhibitors in Bleomycin-induced Lung Injury

Cited by 6 publications

References 52 publications

Pulmonary Protein Oxidation and Oxidative Stress Modulation by Lemna minor L. in Progressive Bleomycin-Induced Idiopathic Pulmonary Fibrosis

Pulmonary Protein Oxidation and Oxidative Stress Modulation by Lemna minor L. in Progressive Bleomycin-Induced Idiopathic Pulmonary Fibrosis

The Effect of Adrenalectomy on Bleomycin-Induced Pulmonary Fibrosis in Mice

Mechanisms of Bleomycin-induced Lung Fibrosis: A Review of Therapeutic Targets and Approaches

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