2. Academic Validation
  3. Poly (ADP-ribose) polymerase pathway inhibitor (Olaparib) upregulates SERCA2a expression and attenuates doxorubicin-induced cardiomyopathy in mice

Poly (ADP-ribose) polymerase pathway inhibitor (Olaparib) upregulates SERCA2a expression and attenuates doxorubicin-induced cardiomyopathy in mice

  • Environ Toxicol Pharmacol. 2023 Sep 7;104261. doi: 10.1016/j.etap.2023.104261.
Rania Gamal Elkatary 1,  Hussein Mahmoud El Beltagy 1,  Vivian Boshra Abdo 1,  Dina Sabry Abd El Fatah 2,  Amr El-Karef 3,  Rehab Hamdy Ashour 4
Affiliations

Affiliations

  • 1 Clinical Pharmacology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
  • 2 Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Egypt.
  • 3 Pathology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
  • 4 Clinical Pharmacology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt. Electronic address: [email protected].
PMID: 37689219 DOI: 10.1016/j.etap.2023.104261
Abstract

The cardiotoxicity induced by doxorubicin is dose-dependent. The present study tested the potential cardioprotective effect of Poly ADP Ribose Polymerase (PARP) pathway inhibitor "olaparib" in a mouse model of doxorubicin-induced cardiomyopathy (DOX-CM). Seventy-two male BALB/c mice were randomized into six equal groups; control, DOX-CM, dexrazoxane-treated, and three olaparib-treated groups (5, 10, and 50mg/kg/day). Cardiomyopathy was assessed by heart weight/Tibial length (HW/TL) ratio, cardiac fibrosis, oxidative stress, and electron microscope. Myocardial expression of SERCA2a mRNA and cleaved PARP-1 protein were also assessed. Similar to dexrazoxane, olaparib (10mg/kg/day) significantly ameliorated oxidative stress, and preserved cardiac structure. It also suppressed myocardial PARP-1 protein expression and boosted SERCA2a mRNA expression. Olaparib (5 or 50mg/kg/day) failed to show comparable effects. The current study detected the cardioprotective effect of olaparib at a dosage of 10mg/kg/day. Also, the present study discovered a new cardioprotective mechanism of dexrazoxane by targeting PARP-1 in the heart.

Keywords

Cardiomyopathy; Dexrazoxane; Doxorubicin; Olaparib; PARP-1 pathway; SERCA2a.

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