The Effect of Intermittent Fasting on Isoproterenol-Induced Myocardial Infarction in Aged Rats: A Potential Role of Autophagy

Abstract

This study was planned to investigate the possible cardioprotective effect of intermittent fasting (IF) in old rats subjected to acute myocardial infarction (MI) by isoproterenol and its underlying mechanisms, including heart and pancreatic autophagy. The present work was carried out on 50 male Wistar rats (10 adults weighing 170-250 grams and 40 aged weighing 255-450 grams), which were divided into five groups: Group 1: Adult group (n=10): Group 2: Old group (n=10): Rats in both Adult and Old groups had free access to food and water-ad-libitum- for 4 weeks. Group 3: Old-intermittent fasting group; Old-F (n=10): Rats in this group were submitted to alternate day fasting. They were fed ad libitum every other day and fasted the following day with free access to water for 4 weeks. On the fasting day, the cages were changed to avoid the presence of remaining pellets. Rats in Adult, Old and Old-F groups were injected with saline for two days at 24 hours interval (on day 27th and 28th). Group 4: Old-isoproterenol group; Old-ISO (n=10): Rats in this group had free access to food and water-ad-libitum- for 4 weeks, then were injected subcutaneously by isoproterenol in a dose of 85 mg/Kg body weight for two days at 24 hours interval (on 27th and 28th day) to induce myocardial infarction. Group 5: Old-intermittent fasting-isoproterenol group; Old-F-ISO (n=10): Rats in this group were submitted to fast every other day for 4 weeks as in group 3, then were injected by isoproterenol as in group 4. All rats were assessed for the changes in body weight (BW); body mass index (BMI); waist circumference (WC); visceral adipose tissue weight (VATW); visceral adipose tissue weight/body weight (VATW/BW); glucose homeostasis parameters, including fasting plasma glucose (FPG), plasma level of fasting insulin (FI), homeostatic model assessment of insulin resistance ( HOMA-IR), and homeostatic model assessment of β-cell function (HOMA-%B), pancreatic autophagy marker, mRNA expression of pancreatic Atg-7; plasma levels of lipid profile, namely triglycerides (TGs), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C),and high density lipoprotein cholesterol (HDL-C); atherogenic index (AI); liver weight (LW) and Liver index; cardiac parameters namely, cardiac injury markers [plasma level of troponin-I, and creatine kinase myocardial band (CK-MB)], cardiac level of oxidative stress markers [malondialdehyde (MDA), reduced glutathione (GSH)], cardiac level of proinflammatory marker [tumor necrosis factor -alpha (TNF-α)], and cardiac autophagy marker [mRNA expression of heart Atg-5]. Histopathological changes in cardiac muscle and liver tissues were also determined.