Electrocardiographic, hemodynamic, and biochemical evidence on the protective effects of exenatide against phosphine-induced cardiotoxicity in rat model

Abstract

Aluminum phosphide (AlP) poisoning can be deadly in most cases targeting the heart. To overcome AlP toxicity, exenatide has been studied in the present study due to its pleiotropic effects on cardiac damages. In this study, the rats were exposed to LD50 of AlP (10 mg/kg) by gavage, and exenatide at doses (0.05, 0.1, and 0.2 mg/kg) injected intraperitoneally 30 min after poisoning. The cardiac parameters including heart rate (HR), blood pressure (BP), QRS, corrected QT (QTc), and ST were monitored for 180 min. Blood glucose level was measured in the study groups 30 min after exenatide injection. Evaluation of biochemical parameters including mitochondrial complexes I, II, and IV activities, adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio, malondialdehyde (MDA), apoptosis, lactate, troponin I, and brain natriuretic peptide (BNP) was done on heart tissues after 12 and 24 h. Additionally, the tissues were analyzed for any pathological damages including necrosis, hemorrhage, or hyperemia 24 h post-treatment. Our results showed that AlP-induced HR, BP, and electrocardiographic changes were improved by exenatide at all doses. The blood glucose levels of poisoned animals reached control levels after exenatide treatment. Besides, treatment with exenatide at all doses improved complexes I and IV activity, ADP/ATP ratio, and apoptosis. Malondialdehyde, lactate, troponin I, and BNP levels were also diminished after exenatide co-treatment in poisoned animals. On the other hand, administration of exenatide doses improved the histopathology of AlP-induced tissues. Based on our findings, exenatide has a protective effect against phosphine-induced cardiotoxicity in an almost dose-dependent way. However, further investigations are needed on the potential clinical use of exenatide in this poisoning.

The electrocardiographic, hemodynamic, echocardiographic, and biochemical evaluation of treatment with edaravone on acute cardiac toxicity of aluminum phosphide

“…Several studies have shown that cardiovascular disorders are the leading cause of death in the first 12–24 h after phosphine poisoning ( Jafari et al, 2015 ; Asghari et al, 2017 ; Bameri et al, 2021 ). Based on some findings from previous studies, intensive oxidative stress, disturbance of electron transport chain (ETC) in mitochondria, interfering with several macromolecules, and apoptosis are the main mechanisms of AlP poisoning ( Armandeh et al, 2021 ; Hooshangi Shayesteh et al, 2022 ).…”

“…Unfortunately, there is no specific antidote for managing the cardiac toxicity effects of AlP to date. The protective impacts of several agents such as cannabidiol ( Hooshangi Shayesteh et al, 2022 ), acetyl- l -carnitine ( Baghaei et al, 2016 ), vasopressin ( Jafari et al, 2015 ), melatonin ( Asghari et al, 2017 ), Mg nanoparticle ( Baeeri et al, 2013 ), triiodothyronine ( Abdolghaffari et al, 2015 ), iron sucrose ( Solgi et al, 2015 ), levosimendan ( Armandeh et al, 2021 ; Baeeri et al, 2022 ), taurine ( Samadi et al, 2021 ), exenatide ( Bameri et al, 2021 ), and minocycline ( Haghi-Aminjan et al, 2018 ) on the cardiac toxicity of phosphine have been investigated. However, there is no entirely effective treatment for the management of AlP-cardiotoxicity.…”

A systematic review on the role of melatonin and its mechanisms on diabetes-related reproductive impairment in non-clinical studies

“…Apoptosis is a controlled cell death playing a crucial role in maintaining cellular homeostasis ( 56 , 57 ). Any disturbances regulating this pathway lead to cellular abnormalities and diseases ( 58 , 59 ).…”

Exenatide regulates Th17/Treg balance via PI3K/Akt/FoxO1 pathway in db/db mice

“…Sixteen 4-week-old male db/db mice were randomly divided into exenatide (n = 8) or control group (n = 8) and maintained in a specific-pathogen free, temperature-controlled environment under 12 h light/dark cycles. Mice in exenatide group received subcutaneous short-acting exenatide (Byetta, Baxter Pharmaceutical Solutions LLC., Indiana, USA) administrations (200 µg/kg body weight) (Bameri et al 2021 ; Tatarkiewicz et al 2013 ). Control mice received an equal volume of saline solution.…”