Grape Seed Proanthocyanidin Ameliorates Cardiac Toxicity Induced by Boldenone Undecylenate through Inhibition of NADPH Oxidase and Reduction in the Expression of NOX2 and NOX4

Abstract

The effect of anabolic androgenic steroids on the cardiovascular system is poorly understood. Increased production of free radicals is coupled to the pathophysiology of many alterations within the circulatory system. The only function of the enzyme family NADPH oxidases (NOXs) is the generation of reactive oxygen species (ROS). Therefore, this study investigated the beneficial role of grape seed proanthocyanidin extract (GSPE) in ameliorating cardiac toxicity induced by the anabolic steroid Boldenone in male rats through NOX inhibition and reduction in the expression of NOX2 and NOX4. This study was conducted on forty male rats which are divided into four groups (normal control, positive control or GSPE, Boldenone, and posttreatment Boldenone with GSPE). A significant increase in relative body weight, relative heart weight, and hemodynamic parameters, as well as serum concentrations of lactate dehydrogenase, creatine kinase, creatine kinase-muscle brain, myoglobin, cholesterol, low-density lipoprotein cholesterol, risk factor 1/2, K+, and Cl−, in treated rats with Boldenone when compared with control. We also noted a significant increase in the levels of cardiac malondialdehyde, H2O2 generation in heart tissues, mRNA expression of NOX2 and NOX4, and immunoreactivity to proliferating cell nuclear antigen (PCNA). Posttreated rats with Boldenone and GSPE ameliorated cardiac toxicity via inhibition of NOX and a reduction in alteration of the expression of NOX2, NOX4, and PCNA induced by Boldenone. These novel insights into the antioxidative activity of GSPE should serve as a basis for the development of improved chemopreventive or therapeutic strategies for cardiac toxicity.

Evaluation of the Cardiac Protection Conferred by Proanthocyanidins in Grape Seeds against Development of Ehrlich Solid Tumors in Mice

“…Furthermore, grape polyphenols were shown by a large number of in vitro, animal, and human studies to have a positive effect on prevalent cardiovascular risk factors [34]. e findings of this study were consistent with those reported by Tousson et al [15], who observed that cardiac toxicity caused by boldenone undecylenate was attenuated by GSPE by suppressing NADPH oxidase and downregulating NOX2 and NOX4 expression. Moreover, based on rodent models, GSPE has been demonstrated by Karthikeyan et al [35] to confer effective cardiac protection by ameliorating myocardial damage caused by isoproterenol.…”

“…us, the control group (G1) consisted of mice that were not treated in any way. e GSPE group (G2) consisted of mice that were administered daily by oral gavage 50 mg/kg GSPE over a period of 14 days [15]. e EST group (G3) consisted of mice that carried EST for a period of 14 days [16].…”

“…Many types of vegetables, seeds, and fruit contain the natural antioxidant proanthocyanidins, which comprises various phenolic compounds [12,13]. Red grape seeds have been found to contain a number of polyphenolic antioxidants, with a proportion of proanthocyanidins of around 89%, including 6.6% dimers, 5% trimers, 2.9% tetramers, and 74.8% oligomers [14,15]. e red grape seed extract known as grape seed proanthocyanidins extract (GSPE) presents various biological qualities, being effective against inflammation, apoptosis, proliferation, oxidants, and oxidative stress [14].…”

Sinapic Acid Attenuates Cardiovascular Disorders in Rats by Modulating Reactive Oxygen Species and Angiotensin Receptor Expression

“…A regulatory complex comprising three protein subunits with different gene encoding, troponin is found on the thin filament of the myocardial contractile mechanism. It is the main biomarker for diagnosing myocardial infarction [43] because increase in its level is exclusively indicative of cardiac damage, whereas increase in CK-MB is not [9,16]. Sorodoc et al [44] reported on a case where all three aspects for diagnosing acute myocardial infarction were present, namely, clinical symptoms, electrocardiographic alterations, and increased levels of the myocardial enzymes CK and CK-MB.…”

“…As the latest discoveries suggest, hypertension, lipid metabolism changes, and other cardiovascular complications occur primarily as a result of oxidative stress. When reactive oxygen species (ROS) are generated in excess, oxidative stress can promote the development of different disorders, including cancer, neurodegenerative conditions, ageing, and CVDs [16,25,26]. Given the above considerations, this work employed L-NAME-induced rats with hypertension to determine how SA affected cardiac functions and structure as well as enzymatic antioxidants and lipid profile levels.…”