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

Abstract

Strategies for treating myocardial ischemia in the clinic usually include re-canalization of the coronary arteries to restore blood supply to the myocardium. However, myocardial reperfusion insult often leads to oxidative stress and inflammation, which in turn leads to apoptosis and necrosis of myocardial cells, for which there are no standard treatment methods. The aim of this study was to determine the pharmacological effect of indole-3-carbinol (I3C), a phytochemical found in most cruciferous vegetables, in a mouse model of myocardial ischemia/reperfusion injury (MIRI). Our results showed that I3C pretreatment (100 mg/kg, once daily, i. p.) prevented the MIRI-induced increase in infarct size and serum creatine kinase (CK) and lactate dehydrogenase (LDH) in mice. I3C pretreatment also suppressed cardiac apoptosis in MIRI mice by increasing the expression levels of the anti-apoptotic protein Bcl-2 and decreasing the expression levels of several apoptotic proteins, including Bax, caspase-3, and caspase-9. In addition, I3C pretreatment was found to reduce the levels of parameters reflecting oxidative stress, such as dihydroethidium (DHE), malondialdehyde (MDA), reactive oxygen species (ROS), and nitric oxide (NO), while increasing the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC) and glutathione (GSH), in MIRI-induced ischemic heart tissue. I3C pretreatment was also able to remarkably decrease the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) mRNA in ischemic heart tissue. These results demonstrate that administration of I3C protects the heart from MIRI through its anti-apoptotic, antioxidant, and anti-inflammatory effects.

Indole-3-carbinol (I3C) reduces apoptosis and improves neurological function after cerebral ischemia–reperfusion injury by modulating microglia inflammation

“…After 2 weeks of habituation, 60 rats were randomly divided into sham-operated group, MCAO group and MCAO + I3C group, 20 rats in each group. I3C (150 mg/kg, once daily) was administered intraperitoneally to the rats on three consecutive days 32 , 33 , immediately after surgery on the first day, and at a fixed time of 12 am on the second and third days after surgery. I3C was formulated at the time of each daily administration and dissolved in Dimethylsulfoxide (DMSO).…”

Synthetic Methodologies and Therapeutic Potential of Indole-3-Carbinol (I3C) and Its Derivatives

“…I3C is an important phytochemical contained in cruciferous vegetables and is able to exert various activities among which are cardioprotective, antioxidant, anti-inflammatory, antiangiogenesis, and antimicrobial activities, the promotion of tumor cell apoptosis [ 4 , 9 ] and, more recently, an important inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS)-CoV-2 viral egression, including the Omicron variant [ 10 , 11 ].…”

Roles of Trimethylamine-N-oxide in Atherosclerosis and Its Potential Therapeutic Aspect: A Literature Review

“…In addition, pretreatment with I3C increased antioxidant parameter levels while decreasing oxidative stress parameters and inflammatory cytokines in MIRI-induced ischemic heart tissue. These results indicate that the anti-apoptotic, antioxidant, and anti-inflammatory properties of I3C treatment protect the heart from MIRI [ 88 ].…”