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.
- 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].
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.
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