A new approach of nano-metformin as a protector against radiation-induced cardiac fibrosis and inflammation via CXCL1/TGF-Β pathway

Heba M. Karam, Dina M. Lotfy, Ayman M. Ibrahim, Farag M. Mosallam, Sahar S. Abdelrahman, Amira Abd-ElRaouf
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Abstract

The present work investigates the potential role of metformin nanoparticles (MTF-NPs) as a radio-protector against cardiac fibrosis and inflammation induced by gamma radiation via CXCL1/TGF-β pathway. Lethal dose fifty of nano-metformin was determined in mice, then 21 rats (male albino) were equally divided into three groups: normal control (G1), irradiated control (G2), and MTF-NPs + IRR (G3). The possible protective effect of MTF-NPs is illustrated via decreasing cardiac contents of troponin, C-X-C motif Ligand 1 (CXCL1), tumor growth factor β (TGF-β), protein kinase B (AKT), and nuclear factor-κB (NF-κB). Also, the positive effect of MTF-NPs on insulin-like growth factor (IGF) and platelet-derived growth factor (PDGF) in heart tissues using immunohistochemical technique is illustrated in the present study. Histopathological examination emphasizes the biochemical findings. The current investigation suggests that MTF-NPs might be considered as a potent novel treatment for the management of cardiac fibrosis and inflammation in patients who receive radiotherapy or workers who may be exposed to gamma radiation.

Graphical Abstract

Abstract Image

纳米二甲双胍通过 CXCL1/TGF-Β 通路抗辐射诱导的心脏纤维化和炎症的新方法
本研究探讨了二甲双胍纳米颗粒(MTF-NPs)通过CXCL1/TGF-β途径作为放射保护剂对伽马射线诱导的心脏纤维化和炎症的潜在作用。首先测定了纳米二甲双胍在小鼠体内的致死剂量50,然后将21只雄性白化大鼠平均分为三组:正常对照组(G1)、辐照对照组(G2)和MTF-NPs + IRR组(G3)。MTF-NPs 可通过降低心肌肌钙蛋白、C-X-C motif Ligand 1(CXCL1)、肿瘤生长因子 β(TGF-β)、蛋白激酶 B(AKT)和核因子-κB(NF-κB)的含量起到保护作用。本研究还利用免疫组化技术说明了 MTF-NPs 对心脏组织中胰岛素样生长因子(IGF)和血小板衍生生长因子(PDGF)的积极影响。组织病理学检查强调了生化检查结果。目前的研究表明,MTF-NPs 可被视为一种有效的新型疗法,用于治疗接受放疗的患者或可能暴露于伽马射线的工人的心脏纤维化和炎症。
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