Anti-Fibrotic Effects of Low Toxic Microcystin-RR on Bleomycin-Induced Pulmonary Fibrosis: A Comparison with Microcystin-LR

Wang, Jie; Ren, Yan; Zheng, Xiufen; Kang, Jiaqi; Huang, Zhongcheng; Xu, Lizhi; Wang, Yaping

doi:10.3389/fphar.2021.675907

Cited by 6 publications

(5 citation statements)

References 45 publications

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“…In the subacute stage, the proliferation and differentiation of fibroblasts and the expression of pro-fibrotic cytokines will appear in the lesion area; there will be a large amount of extracellular matrix deposition and fibrotic lesions [ 35 ]. The BPF mouse model and found that the lungs of the model group showed varying degrees of alveolar structural damage, inflammatory cell infiltration, and a large amount of collagen-based extracellular matrix deposition [ 36 ]. The gene expression test results showed that mouse lung tissue interleukin, collagen gene connective tissue growth factor, and transforming growth factor were all increased to varying degrees compared with those in the normal control group, which was consistent with the histopathological changes of IPF.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary fibrosis model of mice induced by different administration methods of bleomycin

et al. 2023

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Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease of the lung. How to build a typical human mimicking animal model has been a challenge. Thus, to reveal the mechanism and to make it useful for IPF clinical treatment, a different type of mice model and inspection methods are used to evaluate which one is applicable for the study of IPF. Method 69 Twelve-weeks-old C57BL/6 mice were divided into 3 type groups (n = 7 for each control group, n = 8 for each BLM-induced pulmonary fibrosis groups), as intraperitoneal injection, intratracheal administration, and intravenous administration of bleomycin (BLM) to initiate lung fibrosis. Changes of the lung function measured through mice Pulmonary function test (PFT). Morphological changes in mice were observed by PET/CT, Masson and Picro-Sirius staining, Transmission electron microscopy (TEM). Biochemical changes were tested by Enzyme-linked immunosorbent assay (Elisa). Results PET/CT of BLM-receiving mice showed an increase in fibrotic consolidations and an increase in non-aerated lung area in BLM-treated mice compared with that in controls. TGF-b1, TNF-a, IL-6, GM-CSF in BALF and serum. PAI-1, HYP in the lung tissue of mice were significantly different in each BLM groups than those in the controls. The results of Masson staining in mice indicate that the lung tissues of all BLM received groups, the intratracheal groups, the intravenous groups, and the intraperitoneal groups have a higher degree of pulmonary septal thickening and collagen fiber consolidation compare to saline control. Picro-Sirius staining results are consistent with the results of Masson staining. Compared with the saline control group, the ratio of Col 1/Col 3 was significantly increased in each BLM group. TEM results found that in BLM group, type I alveolar epithelial cells were degenerated. Exfoliated endothelial cells were swelling, and type II alveolar epithelial cells were proliferated, the shape of the nucleus was irregular, and some tooth-like protrusions were seen. Conclusions With three different methods of animal model construction, high dose of each show more compliable, and BLM can successfully induce animal models of pulmonary fibrosis, however, certain differences in the fibrosis formation sites of them three, and tail vein injection of BLM induced PF model is closer to the idiopathic pulmonary interstitial fibrosis.

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Section: Discussionmentioning

confidence: 99%

Pulmonary fibrosis model of mice induced by different administration methods of bleomycin

et al. 2023

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“…Histological characteristics documentation and the prevalence of lung parenchymal lesions associated with original tissue loss and collagen fiber accumulation was studied by the Sirius Red, or Elastica-Van Gieson method [47].…”

Section: Histochemical Methods For Detection Of Elastic and Collagen ...mentioning

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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“…Bleomycin (BLM) has a significant effect on proliferation of collagen fibers (Maeda et al, 2016 ; Wang et al, 2021 ). It can induce the proliferation of fibroblasts and the numerous accumulation of collagen fibers (Willenborg et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

The relationship between compensatory hyperplasia of the myodural bridge complex and reduced compliance of the various structures within the cranio‐cervical junction

Song

Gong

et al. 2022

The Anatomical Record

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The myodural bridge complex (MDBC) is described as a functional anatomic structure that involves the dense connective tissue fibers, muscles, and ligaments in the suboccipital region. It has recently been proposed that the MDBC can influence cerebrospinal fluid (CSF) circulation. In the present study, bleomycin (BLM), a type of antibiotic that is poisonous to cells, was injected into the posterior atlanto-occipital interspace (PAOiS) of rats to induce fibrous hyperplasia of structures in PAOiS. Sagittal sections of tissues obtained from the posterioroccipital region of the rats were stained utilizing the Masson Trichrome staining method. Semiquantitative analysis evidenced that the collagen volume fraction of collagen fibers of the MDBC, as well as the sum of the area of the spinal dura mater and the posterior atlanto-occipital membrane in the BLM group were significantly increased (p < .05) compared to that of the other groups. This finding illustrates that the MDBC fibers as well as other tissues in the PAOiS of rats in the BLM group developed fibrotic changes which reduced compliance of the spinal dura mater. Indeed, the sectional area of the rectus capitis dorsal minor muscle in the BLM group was measured to be increased. These changes may further restrict CSF flow. The present research provides support for the recent hypothesis proposed by Labuda et al. concerning the pathophysiology observed in symptomatic adult Chiari malformation Type I patients, that there exists a relationship between the altered compliance of the anatomic structures within the craniocervical region and the resultant compensatory hyperplasia of the MDBC.

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Anti-Fibrotic Effects of Low Toxic Microcystin-RR on Bleomycin-Induced Pulmonary Fibrosis: A Comparison with Microcystin-LR

Cited by 6 publications

References 45 publications

Pulmonary fibrosis model of mice induced by different administration methods of bleomycin

Pulmonary fibrosis model of mice induced by different administration methods of bleomycin

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

The relationship between compensatory hyperplasia of the myodural bridge complex and reduced compliance of the various structures within the cranio‐cervical junction

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