18 March 2020 : Animal Research
Med Sci Monit 2020; 26:e920557
BACKGROUND: Doxorubicin-induced myocardial toxicity is associated with oxidative stress, cardiomyocyte, apoptosis, and loss of contractile function. Previous studies showed that microRNA-375 (miR-375) expression was increased in mouse models of heart failure and clinically, and that inhibition of miR-375 reduced inflammation and increased survival of cardiomyocytes. This study aimed to investigate the effects and mechanisms of inhibition of miR-375 in a mouse model of doxorubicin-induced cardiac toxicity in vivo and in doxorubicin-treated rat and mouse cardiomyocytes in vitro.
MATERIAL AND METHODS: The mouse model of doxorubicin-induced cardiac toxicity was developed using an intraperitoneal injection of doxorubicin (15 mg/kg diluted in 0.9% saline) for eight days. Treatment was followed by a single subcutaneous injection of miR-375 inhibitor. H9c2 rat cardiac myocytes and adult murine cardiomyocytes (AMCs) were cultured in vitro and treated with doxorubicin, with and without pretreatment with miR-375 inhibitor.
RESULTS: Doxorubicin significantly upregulated miR-375 expression in vitro and in vivo, and inhibition of miR-375 re-established myocardial redox homeostasis, prevented doxorubicin-induced oxidative stress and cardiomyocyte apoptosis, and activated the PDK1/AKT axis by reducing the direct binding of miR-375 to 3’ UTR of the PDK1 gene. Inhibition of PDK1 and AKT abolished the protective role of miR-375 inhibition on doxorubicin-induced oxidative damage.
CONCLUSIONS: Inhibition of miR-375 prevented oxidative damage in a mouse model of doxorubicin-induced cardiac toxicity in vivo and in doxorubicin-treated rat and mouse cardiomyocytes in vitro through the PDK1/AKT signaling pathway.
Keywords: Apoptosis, Doxorubicin, Oxidative Stress, Antineoplastic Agents, cardiotoxicity, Cells, Cultured, Mice, Inbred C57BL, MicroRNAs, Myocytes, Cardiac
04 June 2022 : EditorialEditorial: Acute Hepatitis of Unknown Origin in Children. Is Autoimmunity at Play?
Med Sci Monit 2022; 28:e937371
23 Jun 2022 : Clinical ResearchA Real-World Study to Compare the Safety and Efficacy of Paritaprevir/Ombitasvir/Ritonavir and Dasabuvir, w...
Med Sci Monit In Press; DOI: 10.12659/MSM.936706
22 Jun 2022 : Clinical ResearchA Single-Center Study Comparing the Effects of Thoracic Spine Manipulation vs Mobility Exercises in 26 Offi...
Med Sci Monit In Press; DOI: 10.12659/MSM.937316
21 Jun 2022 : Clinical ResearchOptimal Timing and Outcomes of Minimally Invasive Approach in Acute Biliary Pancreatitis
Med Sci Monit In Press; DOI: 10.12659/MSM.937016
Most Viewed Current Articles
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292
01 Nov 2020 : Review articleLong-Term Respiratory and Neurological Sequelae of COVID-19
Med Sci Monit 2020; 26:e928996