Indole-3-carbinol ameliorated the isoproterenol-induced myocardial infarction via multimodal mechanisms in Wistar rats

Abstract

The present study investigated the cardioprotection of Indole-3-carbinol on isoproterenolinduced myocardial infarction in Wistar rats. I3C treatment significantly reduced the prolongation of the QRS complex, QT interval, and ST-segment elevation. I3C was also able to normalise blood pressure (SBP, DBP, and MAP) and HR. I3C significantly decreased heart weight, cardiac troponin I (cTn I), CK-MB, LDH, AST, and ALT. I3C ameliorated acute hyperglycemia, hyperlipidemia, and myocardial infarction (%) in ISO rats. I3C treatment significantly elevated the antioxidant enzymes like SOD, CAT, and GSH and attenuated the MDA levels. I3C reduced the inflammatory cytokines (TNF-α and IL-6) and increased the antiinflammatory cytokine 1L-10. Furthermore, I3C significantly recovered myocardial structure by inhibiting neutrophil infiltration and edema. Moreover, I3C attenuated apoptotic markers (cytochrome C, caspase 9, and caspase 3). Consequently, I3C restored cardiac function in MI rats by alleviating oxidative stress, inflammation, and apoptosis, and I3C could be used to treat myocardial infarction.

Cardioprotective Effect of Taxifolin against Isoproterenol-Induced Cardiac Injury through Decreasing Oxidative Stress, Inflammation, and Cell Death, and Activating Nrf2/HO-1 in Mice

“…This ISO-induced oxidative stress is triggered by disturbed mitochondrial membrane causing leakage of ROS and other free radicals. as well as catecholamine auto-oxidation [ 41 , 42 , 43 ]. Consequently, excessive production of oxidative agents, along with impairment of cardiac antioxidants, mediate oxidative damage of myocyte contents manifested by elevated cardiac lipid peroxidation (LPO) and protein carbonyl, as well as decreased activities of antioxidant mechanism, thereby aggravating myocardial damage and cardiac dysfunction [ 6 , 41 ].…”

Indole-3-Carbinol (I3C) Protects the Heart From Ischemia/Reperfusion Injury by Inhibiting Oxidative Stress, Inflammation, and Cellular Apoptosis in Mice

“…Caspase family proteins play a key role in the pathogenesis of cellular apoptosis in ischemic pathogenesis of the heart ( McIlwain et al, 2013 ). In a previous study, treatment with I3C was found to improve cardiac function in a rat myocardial infarction model by reducing the expression of apoptotic markers such as cytochrome C, caspase-9, and caspase-3 ( Ramakrishna and Krishnamurthy, 2022 ). Our results show that pretreatment with I3C simultaneously increased the expression levels of Bcl-2 and decreased the expression levels of Bax, caspase-3, and caspase-9, thereby contributing to the amelioration of cellular apoptosis in ischemic heart tissue.…”

“…For example, in a model of cardiac toxicity induced by doxorubicin (DOX) in mice, oral I3C administration was found to attenuate pathologically elevated reactive oxygen species (ROS) and lipid peroxidation in cardiac tissue ( Hajra et al, 2018 ). In a rat model of isoproterenol-induced myocardial infarction, I3C treatment restores cardiac function by attenuating oxidative stress and cellular apoptosis ( Ramakrishna and Krishnamurthy, 2022 ). In a heart failure model in mice, I3C supplementation stimulates mitochondrial oxidative capacity by activating peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), or glucose transporter 4 (GLUT4)-mediated glucose uptake ( Beauloye et al, 2011 ; Deng et al, 2014 ).…”

Indole‐3‐carbinol ameliorated the neurodevelopmental deficits in neonatal anoxic injury in rats

“…The experimental animals were randomly divided into the following experimental groups: (1) vehicle‐treated animals exposed to normoxia or control, (2) vehicle‐treated animals exposed to anoxia, (3) anoxic+I3C 7.5 mg/kg, (4) anoxic+I3C 15 mg/kg, (5) anoxic+I3C 30 mg/kg (number of animals [ n ] = 16 for each group). I3C doses for the current study were selected based on previous reports (Paliwal et al, 2018; Ramakrishna & Krishnamurthy, 2022) and a pilot study. The sample size was calculated using G*power analysis (at 80% power), and n = 6 was sufficient to produce a P < 0.05.…”

“…Indole‐3‐carbinol (I3C) is derived from cruciferous vegetables, which exhibit neuroprotection (El‐Naga et al, 2014), and antioxidant properties (Choi et al, 2018; Ramakrishna & Krishnamurthy, 2022). Recent studies report that I3C improves brain function by elevating mitochondrial antioxidant enzymes (Paliwal et al, 2018), ameliorating mitochondrial‐mediated oxidative stress and apoptosis (El‐Naga et al, 2014).…”