Modulating insulin secretion and inflammation against sodium arsenite toxicity by levosimendan as a novel pancreatic islets’ protector

IF 3.3 4区医学 Q2 TOXICOLOGY

Toxin Reviews Pub Date : 2023-04-27 DOI:10.1080/15569543.2023.2205515

M. Daniali, M. Navaei-Nigjeh, M. Baeeri, Soheyl Mirzababaei, M. Gholami, M. Rahimifard, M. Abdollahi

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引用次数: 1

Abstract

Abstract Levosimendan (LEVO) is a calcium sensitizer with established inotropic and vasodilator impacts associated with ATP-sensitive potassium channels (KATP). Although LEVO’s role in modulating oxidative stress of cardiac cells has been studied, in the current study, LEVO was used, for the first time, to investigate its preventive and therapeutic roles in pancreatic islets through viability, functionality, and inflammation pathways as well as oxidative stress against the toxicity induced by sodium arsenite (NaAsO2). Following the optimization studies to select the proper concentrations of LEVO and NaAsO2, isolated pancreatic islets were exposed to different combinations of NaAsO2 and LEVO. MTT assay, glucose-dependent insulin secretion test, investigation of oxidative stress and inflammation biomarkers in addition to qualification of the expressions of P16, P38, and NF-κB genes were performed to assess different underlying mechanisms to investigate the protective role of LEVO against NaAsO2-induced toxicity. This study demonstrated that NaAsO2-treated pancreatic islets’ exposure to LEVO improved their viability and functionality while modulating the generation of oxidative stress and inflammatory biomarkers. Therefore LEVO caused significant recoveries in the characteristics of the islets. The main conclusion is that LEVO showed protective impacts in pancreatic islets against exposure to NaAsO2. However, therapeutic uses of LEVO in the field of diabetes need further investigations. HIGHLIGHTS Sodium arsenite is responsible for activating the oxidative stress and inflammation pathways in pancreatic islet cells and consequently decreasing their viability and function. Treatment of pancreatic islets with sodium arsenite results in the loss of glucose-dependent insulin secretion (GDIS) which can be alleviated by levosimendan. Levosimendan modulates the decreased level of secreted insulin by preventing formation of reactive oxygen species (ROS) and inactivating the inflammatory biomarkers. Levosimendan improves the viability and function of sodium arsenite-treated pancreatic islets by modulating insulin secretion and glucose control. Levosimendan acts as a protective agent against the toxicity induced by sodium arsenite in pancreatic islets through modulating the viability, oxidative stress, inflammation, and function pathways. Graphical Abstract

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新型胰岛保护剂左西孟旦对亚砷酸钠毒性胰岛素分泌和炎症的调节作用

摘要Levosimendan（LEVO）是一种钙增敏剂，具有与ATP敏感性钾通道（KATP）相关的变力和舒张作用。尽管LEVO在调节心脏细胞氧化应激中的作用已被研究，但在当前的研究中，LEVO首次被用于通过生存能力、功能和炎症途径以及氧化应激对抗亚砷酸钠（NaAsO2）诱导的毒性来研究其在胰岛中的预防和治疗作用。在选择适当浓度的LEVO和NaAsO2的优化研究之后，将分离的胰岛暴露于NaAsO2和LEVO的不同组合。MTT法、葡萄糖依赖性胰岛素分泌试验、氧化应激和炎症生物标志物的研究以及P16、P38和NF-κB基因的表达鉴定，以评估不同的潜在机制，从而研究LEVO对NaAsO2诱导的毒性的保护作用。这项研究表明，NaAsO2处理的胰岛暴露于LEVO提高了其生存能力和功能，同时调节了氧化应激和炎症生物标志物的产生。因此，LEVO使小岛的特性显著恢复。主要结论是，LEVO对暴露于NaAsO2的胰岛具有保护作用。然而，LEVO在糖尿病领域的治疗用途需要进一步研究。亮点亚砷酸钠负责激活胰岛细胞的氧化应激和炎症途径，从而降低其生存能力和功能。用亚砷酸钠治疗胰岛会导致葡萄糖依赖性胰岛素分泌（GDIS）的损失，左西孟旦可以减轻这种损失。左西孟丹通过防止活性氧（ROS）的形成和灭活炎症生物标志物来调节分泌胰岛素水平的降低。左西孟丹通过调节胰岛素分泌和葡萄糖控制，改善亚砷酸钠治疗的胰岛的生存能力和功能。左西孟丹通过调节胰岛的活力、氧化应激、炎症和功能途径，对亚砷酸钠诱导的胰岛毒性起到保护作用。图形摘要

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来源期刊

Toxin Reviews 医学-毒理学

CiteScore

6.80

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Toxin Reviews provides an international forum for publishing state-of-the-art reviews and guest-edited single topic special issues covering the multidisciplinary research in the area of toxins derived from animals, plants and microorganisms. Our aim is to publish reviews that are of broad interest and importance to the toxinology as well as other life science communities. Toxin Reviews aims to encourage scientists to highlight the contribution of toxins as research tools in deciphering molecular and cellular mechanisms, and as prototypes of therapeutic agents. Reviews should emphasize the role of toxins in enhancing our fundamental understanding of life sciences, protein chemistry, structural biology, pharmacology, clinical toxinology and evolution. Prominence will be given to reviews that propose new ideas or approaches and further the knowledge of toxinology.