Antiapoptotic and anti‐inflammatory effects of Pparγ agonist, pioglitazone, reversed Dox‐induced cardiotoxicity through mediating of miR‐130a downregulation in C57BL/6 mice. Issue 6 (28th March 2022)

• Record Type: Journal Article
• Authors: Pakravan, Golnaz; Peymani, Maryam; Abedpoor, Navid; Safaeinejad, Zahra; Yadegari, Mehrdad; Derakhshan, Maryam; Nasr Esfahani, Mohammad Hossein; Ghaedi, Kamran
• Is Part Of: Journal of biochemical and molecular toxicology. Volume 36:Issue 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-28
• Subjects: doxorubicin -- GW9662 -- miR‐130a -- pioglitazone -- Pparγ; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Toxicology -- Periodicals; 574
• DOI: 10.1002/jbt.23041
• Languages: English
• ISSNs: 1095-6670

Abstract

Abstract: Doxorubicin (Dox) is an antitumor agent widely used in cancer therapy, with notable side effects of cardiac toxicity. Peroxisome proliferator‐activated receptor γ (PPARγ), is a transcriptional factor with antiapoptotic and anti‐inflammatory properties. Recently we indicated that cardiac toxicity of Dox was due to upregulation of miR‐130a and further suppressive effect on cardiac Pparγ in vitro. In this study, we extended our proposed hypothesis in vivo. To achieve this, pioglitazone (Pio) and GW9662 were used as the specific agonist and antagonist of Pparγ to treat Dox‐injected mice. Heart function, apoptosis, and inflammation in heart tissue were studied. Pretreatment of Dox‐injected mice with Pio resulted in elevated expression of Pparγ and suppression of miR‐130a. However, GW9662 pretreatment was unable to increase miR‐130a expression. Pio pretreatment led to partially cardiac toxicity limitation of Dox whereas GW9662 caused heart damage. Finally, our observation determined that activation of Pparγ was not adequate to reverse the Dox‐induced toxicity completely.