Melatonin Attenuates Dasatinib-Aggravated Hypoxic Pulmonary Hypertension via Inhibiting Pulmonary Vascular Remodeling

Wang, Rui; Pan, Jinjin; Han, Jinzhen; Gong, Miaomiao; Liu, Liang; Zhang, Yunlong; Liu, Ying; Wang, Dingyou; Tang, Qing; Wu, Na; Wang, Lin; Yan, Jinsong; Li, Hua; Yuan, Yuhui

doi:10.3389/fcvm.2022.790921

Cited by 9 publications

(5 citation statements)

References 63 publications

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“…Increased ROS further reduces the synthesis of NO by inhibiting eNOS activity to aggravate vascular endothelial OS injury, which promotes the proliferation and migration of vascular smooth muscle cells and accelerates vascular remodeling. In our study, OS was found activated in both lung tissues of PAH rats and hypoxia-stimulated PMECs, which was consistent with data presented by Wang [ 23 ] and Yu [ 24 ]. After PHN-20 treatment, OS was signally repressed in both lung tissues of PAH rats and hypoxia-stimulated PMECs, implying that the alleviative effect of PHN-20 against PAH might be correlated with the inhibition of OS.…”

Section: Discussionsupporting

confidence: 93%

Phoenixin 20 ameliorates pulmonary arterial hypertension via inhibiting inflammation and oxidative stress

Chai,

Gu,

Zhang

et al. 2024

Aging

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Pulmonary arterial hypertension (PAH) is a severe pathophysiological syndrome resulting in heart failure, which is found to be induced by pulmonary vascular remodeling mediated by oxidative stress (OS) and inflammation. Phoenixin-20 (PNX-20) is a reproductive peptide first discovered in mice with potential suppressive properties against OS and inflammatory response. Our study will explore the possible therapeutic functions of PHN-20 against PAH for future clinical application. Rats were treated with normal saline, PHN-20 (100 ng/g body weight daily), hypoxia, hypoxia+PHN-20 (100 ng/g body weight daily), respectively. A signally elevated RVSP, mPAP, RV/LV + S, and W%, increased secretion of cytokines, enhanced malondialdehyde (MDA) level, repressed superoxide dismutase (SOD) activity, and activated NLRP3 signaling were observed in hypoxia-stimulated rats, which were notably reversed by PHN-20 administration. Pulmonary microvascular endothelial cells (PMECs) were treated with hypoxia with or without PHN-20 (10 and 20 nM). Marked elevation of inflammatory cytokine secretion, increased MDA level, repressed SOD activity, and activated NLRP3 signaling were observed in hypoxia-stimulated PMECs, accompanied by a downregulation of SIRT1. Furthermore, the repressive effect of PHN-20 on the domains-containing protein 3 (NLRP3) pathway in hypoxia-stimulated PMECs was abrogated by sirtuin1 (SIRT1) knockdown. Collectively, PHN-20 alleviated PAH via inhibiting OS and inflammation by mediating the transcriptional function of SIRT1.

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Section: Discussionsupporting

confidence: 93%

Phoenixin 20 ameliorates pulmonary arterial hypertension via inhibiting inflammation and oxidative stress

Chai,

Gu,

Zhang

et al. 2024

Aging

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“…It has the capacity for proliferation, anti-inflammatory, and anti-apoptotic properties (Frungieri et al 2017). Melatonin is now used in many pathophysiological fields because of its ability to interact with cells from the immune and cardiovascular systems and its significant role in the regulation of glucose and metabolic disorders (Navarro-Alarc ón et al 2014; Cho et al 2021;Wang et al 2022b). Because of its ability to cross physiological barriers, such as the blood-testis barrier (Venditti et al 2021), exogenous melatonin can reach the testis in a certain concentration (Álvarez-Fernández et al 2023).…”

Section: Discussionmentioning

confidence: 99%

Melatonin improves the ability of spermatozoa to bind with oocytes in the mouse

Liu

YuSheng

Wang

et al. 2023

Reprod. Fertil. Dev.

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Context and aims Melatonin is a powerful antioxidant regulating various biological functions, including alleviating male reproductive damage under pathological conditions. Here, we aim to analyse the effect of melatonin on normal male reproduction in mice. Methods Male mice received an intraperitoneal injection of melatonin (10 mg/kg body weight) for 35 consecutive days. The testis and epididymis morphology, and epididymal sperm parameters were examined. PCNA, HSPA2, SYCP3, ZO-1 and CYP11A1 expressions in epididymis or testis were detected by immunohistochemistry or Western blotting. Male fertility was determined by in vivo and in vitro fertilisation (IVF) experiments. The differentially expressed sperm proteins were identified by proteomics. Key results No visible structural changes and oxidative damage in the testis and epididymis, and no significant side effects on testis weight, testosterone levels, sperm motility, and sperm morphology were observed in the melatonin-treatment group compared with the control group. Spermatogenesis-related molecules of PCNA, SYCP3, ZO-1, and CYP11A1 showed no significant differences in melatonin-treated testis. However, PCNA and HSPA2 increased their expressions in the epididymal initial segments in the melatonin-treatment group. Normal sperm fertilisation, two-cell and blastocyst development were observed in the melatonin-treated group, but melatonin significantly enhanced the sperm binding ability characterised as more sperm binding to one oocyte (control 7.2 ± 1.3 versus melatonin 11.8 ± 1.5). Sperm proteomics demonstrated that melatonin treatment enhanced the biological process of cell adhesion in sperm. Conclusions and implications This study suggests that melatonin can promote sperm maturation and sperm function, providing important information for further research on the physiological function and protective effect of melatonin in male reproduction.

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“…However, PPHN lambs treated with melatonin showed improved pulmonary vasodilation and decreased pulmonary arterial pressure, enhanced SOD and CAT expression, and decreased generation of superoxide anions and NADPH oxidases in RV [61,62]. In a rat model of hypoxic PH melatonin was shown to attenuate pulmonary pressure and vascular remodeling, decreasing XO activity, MDA levels, NOX4 expression, and increasing CAT, GPx and SOD activities [63].…”

Section: Melatoninmentioning

confidence: 96%

Oxidative Stress and Antioxidant Therapy in Pulmonary Hypertension

et al. 2023

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Pulmonary hypertension (PH) is a progressive disease characterized by elevated artery pressures and pulmonary vascular resistance. Underlying mechanisms comprise endothelial dysfunction, pulmonary artery remodeling and vasoconstriction. Several studies have shown evidence of the critical role of oxidative stress in PH pathophysiology. Alteration of redox homeostasis produces excessive generation of reactive oxygen species, inducing oxidative stress and the subsequent alteration of biological molecules. Exacerbations in oxidative stress production can lead to alterations in nitric oxide signaling pathways, contributing to the proliferation of pulmonary arterial endothelial cells and smooth muscle cells, inducing PH development. Recently, antioxidant therapy has been suggested as a novel therapeutic strategy for PH pathology. However, the favorable outcomes observed in preclinical studies have not been consistently reproduced in clinical practice. Therefore, targeting oxidative stress as a therapeutic intervention for PH is an area that is still being explored. This review summarizes the contribution of oxidative stress to the pathogenesis of the different types of PH and suggests antioxidant therapy as a promising strategy for PH treatment.

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Melatonin Attenuates Dasatinib-Aggravated Hypoxic Pulmonary Hypertension via Inhibiting Pulmonary Vascular Remodeling

Cited by 9 publications

References 63 publications

Phoenixin 20 ameliorates pulmonary arterial hypertension via inhibiting inflammation and oxidative stress

Phoenixin 20 ameliorates pulmonary arterial hypertension via inhibiting inflammation and oxidative stress

Melatonin improves the ability of spermatozoa to bind with oocytes in the mouse

Oxidative Stress and Antioxidant Therapy in Pulmonary Hypertension

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