Antioxidant and antiapoptotic effects of proanthocyanidin and ginkgo biloba extract against doxorubicin‐induced cardiac injury in rats

Abstract

Grape seed proanthocyanidins (GSPE) and ginkgo biloba extract (EGb761) are considered to have protective effects against several diseases. The cardiotoxicity of doxorubicin (DOX) has been reported to be associated with oxidative damage. This study was conducted to evaluate the cardioprotective effects of GSPE and EGb761 against DOX-induced heart injury in rats. DOX was administered as a single i.p. dose (20 mg kg(-1)) to adult male rats. DOX-intoxicated rats were orally administered GSPE (200 mg kg(-1) day(-1)) or EGb761 (100 mg kg(-1) day(-1)) for 15 consecutive days, starting 10 days prior DOX injection. DOX-induced cardiotoxicity was evidenced by a significant increase in serum aspartate transaminase (AST), creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), total cholesterol (TC) and triglyceride (TG) activities and levels. Increased oxidative damage was expressed by the depletion of cardiac reduced glutathione (GSH), elevation of cardiac total antioxidant (TAO) level and accumulation of the lipid peroxidation product, malondialdehyde (MDA). Significant rises in cardiac tumour necrosis factor-alpha (TNF-α) and caspase-3 levels were noticed in DOX-intoxicated rats. These changes were ameliorated in the GSPE and EGb761-treated groups. Histopathological analysis confirmed the cardioprotective effects of GSPE and EGb761. In conclusion, GSPE and EGb761 mediate their protective effect against DOX-induced cardiac injury through antioxidant, anti-inflammatory and antiapoptotic mechanisms.

Cardioprotective Effect of Grape Seed Extract on Chronic Doxorubicin-Induced Cardiac Toxicity in Wistar Rats

“…Further confirmation comes from another study showing that GSE treatment in combination with DOX in mice significantly protected the heart tissue by improving its antioxidant activity; leading to this conclusion that GSE acts as a potent antioxidant to prevent heart damage. 27,39 In the line with this evidence, Karthikeyan et al have confirmed the efficacy of GSPE as a cardioprotective agent in alleviating isoproterenol-induced myocardial injury in rats. 40 They demonstrated that GSPE administration at doses of 100 and 150 mg/kg positively alters the levels of glutathione, ascorbic acid, a-tocopherol, ceruloplasmin, mitochondrial cytochrome, phospholipids and adenosine triphosphate and also restores normal mitochondrial function.…”

“…The animal model used in this study was described previously 21 and characterized by injuries similar to what reported by others. 17,18,[25][26][27] Alterations in physiological parameters are well known as one of the toxic effects of DOX, which is characterized by reduced body and heart weights. [28][29][30] Our findings here confirmed the literature reports that DOX treatment leads to decreased both body and heart weights in animals 31 and that GSE treatment increased body and heart weights, as compared to DOX group.…”

“…Our data confirmed previous findings suggesting GSE attenuated the detrimental impacts of DOX on morphology and ultrastructure of heart tissues in histopathology studies. 27,31 Furthermore, the results of the MTT assay indicated that DOX exerts a dose-dependent cytotoxic effect on MCF7 cells and that GSE treatment in combination with DOX had no significant effect on DOX-induced cell toxicity and GSE alone showed cytotoxicity effect on MCF7 cells. 50 In addition, it was reported that procyanidin, an antioxidant flavonoid of the GSE, exhibited antitumor activity on MCF7 cells.…”

Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats

“…Doxorubicin increases myocardial lipid peroxidation and decreases glutathione peroxidase levels early in doxorubicin cardiotoxicity [12,13]. Myocardium is more susceptible to oxidative damage than other tissues as it contains low levels of catalase and glutathione peroxidase.…”

Proliposomes containing a bile salt for oral delivery of Ginkgo biloba extract: Formulation optimization, characterization, oral bioavailability and tissue distribution in rats

“…G. biloba extract (GbE), isolated from the dried leaves of G. biloba, has been reported to have many beneficial activities, including free radical scavenging (Wang et al, 2010), antioxidative (Boghdady, 2013), anti-inflammatory (Chen et al, 2013b), anti-tumor activities (Tsai et al, 2014), and neuroprotective effects (Abd-Elhady et al, 2013). GbE has become one of the best-selling botanical supplements in many European countries and in the USA for the prevention and adjunctive treatment of vascular and cognitive diseases, such as Alzheimer's disease (Oken et al, 1998;Tchantchou et al, 2007), vertigo (Hamann, 2007;Sokolova et al, 2014), tinnitus (Hilton et al, 2013;Tziridis et al, 2014), and peripheral arterial occlusive diseases (Unger, 2013;Wang et al, 2007).…”