Intermittent Fasting Attenuates Apoptosis, Modulates Autophagy and Preserve Telocytes in Doxorubicin Induced Cardiotoxicity in Albino Rats: A Histological Study

Abstract

Background: Doxorubicin (DOX) is an effective anticancer drug, however its use is limited due to severe cardiotoxic effects as ventricular dysfunction, cardiomyopathy and heart failure. Intermittent fasting (IF) has a potential preventive and therapeutic effects against variety of diseases including cardiovascular and neurodegenerative disorders.Aim of Work: Investigating the effects of DOX on the histological structure of myocardium and evaluating the possible cardioprotective effects of IF on these changes.Materials and Methods: Forty eight adult male albino rats were divided equally into four groups: control, fasting (16 hours fasting /8 hours eating), DOX (received 3 mg/kg every other day for a total of six intraperitoneal injections) and fasting DOX. Body weight, levels of cardiac biomarkers, Malondialdehyde (MDA) and autophagic indicators (LC3II & p62) were measured. Myocardial specimens were processed for paraffin blocks and stained with H&E, Mallory’s trichrome and immunohistochemical stains for p53. Moreover, resin blocks were processed for semithin and ultrathin sections examination. Morphometric and statistical studies were performed.Results: In DOX group, cardiac biomarkers, MDA, LC3II and p62 levels were significantly elevated compared to control group. In addition to, marked histological alterations in myocytes, telocytes and autophagic process. Also, there was significant decrease in cardiomyocytes diameter, significant increase in p53 positive cells and area percent of collagen fibres versus control. On the other hand, IF protected cardiac tissues against the toxic effects of DOX as evidenced by amelioration of histopathological changes and the non significant difference in the levels of cardiac enzymes, MDA, LC3II and p62, cardiomyocytes diameter, p53 positive expressions and area percent of collagen fibres compared to control group.Conclusion: Doxorubicin administration resulted into deleterious effects on the myocardium. Intermittent fasting had cardioprotective effects against Dox-induced cardiotoxicity via restoration of oxidative state, attenuation of apoptosis, regulation of autophagic process and preservation of telocytes.