Naringenin protects cardiac hypercholesterolemia-induced oxidative stress and subsequent necroptosis in rats.
BACKGROUND
In earlier studies, the supplementation of the natural compound Naringenin (NGEN), improved the liver oxidative and inflammatory status, which indicates its direct effect via inhibition of the nuclear factor κB pathway on high cholesterol-induced hepatic damages. In this regard, the present study highlights the mechanisms associated with the protective efficacy of NGEN in the heart tissue of hypercholesterolemic diet rats.


RESULTS
The animals exposed to a high cholesterol diet (HCD) for 90 days exhibited a significant increase in the levels of serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities, nitric oxide (NO) levels, protein and lipid oxidative markers and cardiac lipids profile. Moreover, hypercholesterolemia decreased the levels of enzymatic and non enzymatic antioxidants associated with mitochondrial dysfunctions as proved by the decrease in the mitochondrial complexes in comparison to controls. Importantly, cholesterol-feeding significantly increased myocardial reactive oxygen species (ROS) and nuclear DNA damage and led to the activation of gene expression of the tumor necrosis factor-α (TNF-α) and receptor-interacting protein kinase 3 (RIP3) mRNA that contributed to the elucidation of cholesterol-induced necroptosis, a recently described type of programmed necrosis, in the cardiac tissue.


CONCLUSIONS
Our results show that the co-administration of NGEN (50 mg/kg/bw) in HCD rats improved all the altered parameters and provided insight into a possible molecular mechanism underlying NGEN suppression of necroptosis pathway in the heart.
Toxicology-Microbiology and Environmental Health Unit (UR11ES70), Faculty of Sciences, University of Sfax, Tunisia. Electronic address: yacine_chtourou@topnet.tn.
Yassine
Y
Chtourou
Toxicology-Microbiology and Environmental Health Unit (UR11ES70), Faculty of Sciences, University of Sfax, Tunisia.
Ahlem Ben
AB
Slima
Toxicology-Microbiology and Environmental Health Unit (UR11ES70), Faculty of Sciences, University of Sfax, Tunisia.
Mohamed
M
Makni
Toxicology-Microbiology and Environmental Health Unit (UR11ES70), Faculty of Sciences, University of Sfax, Tunisia.
Radhouane
R
Gdoura
Toxicology-Microbiology and Environmental Health Unit (UR11ES70), Faculty of Sciences, University of Sfax, Tunisia.
Hamadi
H
Fetoui
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006937:Hypercholesterolemia / Q000378:metabolism*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000975:Antioxidants; D015415:Biomarkers; D044950:Flavanones; D020011:Protective Agents; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C582791:Ripk3 protein, rat; C005273:naringenin
Heart; Hypercholesterolemia; Naringenin; Necroptosis; Oxidative stress