Histopathological, physiological and biochemical assessment of resveratrol nanocapsules efficacy in bleomycin-induced acute and chronic lung injury in rats

Albanawany, Neama M; Samy, Doaa M.; Zahran, Noha; El‐Moslemany, Riham M.; Elsawy, Shefaa Mf; Nazel, Maha W Abou

doi:10.1080/10717544.2022.2105445

Cited by 18 publications

(11 citation statements)

References 64 publications

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“…Histological improvement in PFD, LOS, and combined LOS + PFD received groups confirmed the more potent anti-fibrotic effects of the LOS + PFD combination compared to single therapy. Our results agreed with previous literature showing the fibrotic effect of BLM in lung tissue 20 , 34 . It has been shown that PFD induces an anti-fibrotic impact on the PQ fibrosis model 9 , 13 .…”

Section: Discussionsupporting

confidence: 93%

Combination of losartan with pirfenidone: a protective anti-fibrotic against pulmonary fibrosis induced by bleomycin in rats

Amirkhosravi,

Mirtajaddini Goki,

Heidari

et al. 2024

Sci Rep

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Pirfenidone (PFD), one acceptable medication for treating idiopathic pulmonary fibrosis (IPF), is not well tolerated by patients at full doses. Hence, employing of some approaches such as combination therapy may be applicable for increasing therapeutic efficacy of PFD. Losartan (LOS), an angiotensin II receptor antagonist, could be a suitable candidate for combination therapy because of its stabilizing effect on the pulmonary function of IPF patients. Therefore, this study aimed to investigate the effects of LOS in combination with PFD on bleomycin (BLM)-induced lung fibrosis in rats. BLM-exposed rats were treated with LOS alone or in combination with PFD. The edema, pathological changes, level of transforming growth factor-β (TGF-β1), collagen content, and oxidative stress parameters were assessed in the lung tissues. Following BLM exposure, the inflammatory response, collagen levels, and antioxidant markers in rat lung tissues were significantly improved by PFD, and these effects were improved by combination with LOS. The findings of this in vivo study suggest that the combined administration of PFD and LOS may provide more potent protection against IPF than single therapy through boosting its anti-inflammatory, anti-fibrotic, and anti-oxidant effects. These results hold promise in developing a more effective therapeutic strategy for treating of lung fibrosis.

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Section: Discussionsupporting

confidence: 93%

Combination of losartan with pirfenidone: a protective anti-fibrotic against pulmonary fibrosis induced by bleomycin in rats

Amirkhosravi,

Mirtajaddini Goki,

Heidari

et al. 2024

Sci Rep

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“…The specific timing of therapeutic drug intervention may be influenced by animal strain, dose, and method of bleomycin administration. The induction dose of bleomycin varies depending on the animal species, and the commonly used dose reported in the literature for rats is 5–10 mg/kg [ 46 , 47 ]. Referring to the dose–response effect of bleomycin on inflammation and fibrosis [ 48 ], we attempted to induce a fibrosis model by infusion of 10 mg/kg bleomycin in the pre-experiment.…”

Section: Discussionmentioning

confidence: 99%

Qingfei Tongluo Mixture Attenuates Bleomycin-Induced Pulmonary Inflammation and Fibrosis through mTOR-Dependent Autophagy in Rats

Ge,

Guo,

Xiao

et al. 2024

Mediators of Inflammation

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As an interstitial fibrosis disease characterized by diffuse alveolitis and structural alveolar disorders, idiopathic pulmonary fibrosis (IPF) has high lethality but lacks limited therapeutic drugs. A hospital preparation used for the treatment of viral pneumonia, Qingfei Tongluo mixture (QFTL), is rumored to have protective effects against inflammatory and respiratory disease. This study aims to confirm whether it has a therapeutic effect on bleomycin-induced IPF in rats and to elucidate its mechanism of action. Male SD rats were randomly divided into the following groups: control, model, CQ + QFTL (84 mg/kg chloroquine (CQ) + 3.64 g/kg QFTL), QFTL-L, M, H (3.64, 7.28, and 14.56 g/kg, respectively) and pirfenidone (PFD 420 mg/kg). After induction modeling and drug intervention, blood samples and lung tissue were collected for further detection. Body weight and lung coefficient were examined, combined with hematoxylin and eosin (H&E) and Masson staining to observe lung tissue lesions. The enzyme-linked immunosorbent assay (ELISA) and the hydroxyproline (HYP) assay kit were used to detect changes in proinflammatory factors (transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β)) and HYP. Immunohistochemistry and Western blotting were performed to observe changes in proteins related to pulmonary fibrosis (α-smooth muscle actin (α-SMA) and matrix metalloproteinase 12 (MMP12)) and autophagy (P62 and mechanistic target of rapamycin (mTOR)). Treatment with QFTL significantly improved the adverse effects of bleomycin on body weight, lung coefficient, and pathological changes. Then, QFTL reduced bleomycin-induced increases in proinflammatory mediators and HYP. The expression changes of pulmonary fibrosis and autophagy marker proteins are attenuated by QFTL. Furthermore, the autophagy inhibitor CQ significantly reversed the downward trend in HYP levels and α-SMA protein expression, which QFTL improved in BLM-induced pulmonary fibrosis rats. In conclusion, QFTL could effectively attenuate bleomycin-induced inflammation and pulmonary fibrosis through mTOR-dependent autophagy in rats. Therefore, QFTL has the potential to be an alternative treatment for IPF in clinical practice.

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“…The control group received an equivalent volume of normal saline via tracheal and tail root injection, serving as the negative control. The resveratrol dosage was determined based on prior research findings [ 30 ]. All animals were euthanized 24 h after the final resveratrol treatment.…”

Section: Methodsmentioning

confidence: 99%

Resveratrol attenuates inflammation and fibrosis in rheumatoid arthritis-associated interstitial lung disease via the AKT/TMEM175 pathway

Liu,

Fan,

Shao

et al. 2024

J Transl Med

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Background and purpose Interstitial lung disease (ILD) represents a significant complication of rheumatoid arthritis (RA) that lacks effective treatment options. This study aimed to investigate the intrinsic mechanism by which resveratrol attenuates rheumatoid arthritis complicated with interstitial lung disease through the AKT/TMEM175 pathway. Methods We established an arthritis model by combining chicken type II collagen and complete Freund’s adjuvant. Resveratrol treatment was administered via tube feeding for 10 days. Pathological changes in both the joints and lungs were evaluated using HE and Masson staining techniques. Protein expression of TGF-β1, AKT, and TMEM175 was examined in lung tissue. MRC-5 cells were stimulated using IL-1β in combination with TGF-β1 as an in vitro model of RA-ILD, and agonists of AKT, metabolic inhibitors, and SiRNA of TMEM175 were used to explore the regulation and mechanism of action of resveratrol RA-ILD. Results Resveratrol mitigates fibrosis in rheumatoid arthritis-associated interstitial lung disease and reduces oxidative stress and inflammation in RA-ILD. Furthermore, resveratrol restored cellular autophagy. When combined with the in vitro model, it was further demonstrated that resveratrol could suppress TGF-β1 expression, and reduce AKT metamorphic activation, consequently inhibiting the opening of AKT/MEM175 ion channels. This, in turn, lowers lysosomal pH and enhances the fusion of autophagosomes with lysosomes, ultimately ameliorating the progression of RA-ILD. Conclusion In this study, we demonstrated that resveratrol restores autophagic flux through the AKT/MEM175 pathway to attenuate inflammation as well as fibrosis in RA-ILD by combining in vivo and in vitro experiments. It further provides a theoretical basis for the selection of therapeutic targets for RA-ILD. Graphical Abstract

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Histopathological, physiological and biochemical assessment of resveratrol nanocapsules efficacy in bleomycin-induced acute and chronic lung injury in rats

Cited by 18 publications

References 64 publications

Combination of losartan with pirfenidone: a protective anti-fibrotic against pulmonary fibrosis induced by bleomycin in rats

Combination of losartan with pirfenidone: a protective anti-fibrotic against pulmonary fibrosis induced by bleomycin in rats

Qingfei Tongluo Mixture Attenuates Bleomycin-Induced Pulmonary Inflammation and Fibrosis through mTOR-Dependent Autophagy in Rats

Resveratrol attenuates inflammation and fibrosis in rheumatoid arthritis-associated interstitial lung disease via the AKT/TMEM175 pathway

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