Grape seed proanthocyanidin extract protects against perfluorooctanoic acid-induced hepatotoxicity by attenuating inflammatory response, oxidative stress and apoptosis in mice

Liu, Wenwen; Xu, Chao-Jiang; Sun, Xi; Kuang, Haibin; Kuang, Xiaodong; Wu, Zhongze; Yang, Bei; Wu, Lei; Liu, Fangming; Zou, Ting; Zhang, Dalei

doi:10.1039/c5tx00260e

Cited by 27 publications

(15 citation statements)

References 47 publications

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“…Cleavage of caspase-3, a primary executioner of apoptosis, is the ultimate downstream event common to all three pathways (Kwak, 2013), and is therefore considered as a marker of cell apoptosis. In the present study, we showed that GSPE treatment significantly reduced the cleavage of caspase-3 induced by histones stimulation which is consistent with the anti-apoptotic effect of GSPE previously observed in the perfluorooctanoic acid-induced hepatotoxicity model (Liu et al, 2016). In addition, several other natural antioxidants, such as Bauhinia championii flavone, cyanidin-3-glucoside, and N -acetyl cysteine (NAC) have been previously reported to exert anti-apoptotic effects in cardiomyocytes (Jian et al, 2016), neurons (Ke et al, 2011), and human lymphocytes (Han et al, 2004), respectively.…”

Section: Discussionsupporting

confidence: 92%

Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis

Chang

Cauvi

et al. 2017

PeerJ

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Apoptosis of lymphocytes is associated with immunosuppression and poor prognosis in sepsis. Our previous report showed that histones, nuclear proteins released from damaged or dying cells in sepsis, can mediate lymphocyte apoptosis via mitochondria damage. Grape seed proanthocyanidin extract (GSPE), a natural substance with protective properties against oxidative stress, plays a vital role in cell and mitochondria protection. We thus hypothesized that GSPE may play a protective role in histone-induced lymphocyte apoptosis through its anti-oxidative properties. In this study, we investigated the protective efficacy of GSPE on lymphocyte apoptosis induced by extracellular histones, a main contributor of death in sepsis. Human blood lymphocytes were treated with 50 μg/ml histones, 2 μg/ml GSPE, or a combination of both. A total of 100 μM N-acetylcysteine (NAC), a reactive oxygen species (ROS) inhibitor, was used as a positive control for GSPE. Apoptosis, intracellular ROS levels, mitochondrial membrane potential, Bcl-2 expression, and caspase-3 cleavage were measured. Our data clearly indicate that GSPE significantly inhibited lymphocyte apoptosis, generation of ROS, the loss of mitochondrial membrane potential, the decrease in Bcl-2 expression, and caspase-3 activation induced by extracellular histones. In conclusion, we show that GSPE has a protective effect on lymphocyte apoptosis induced by extracellular histones. This study suggests GSPE as a potential therapeutic agent that could help reduce lymphocyte apoptosis, and thus the state of immunosuppression was observed in septic patients.

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Section: Discussionsupporting

confidence: 92%

Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis

Chang

Cauvi

et al. 2017

PeerJ

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“…Several studies have demonstrated that GSE can induce both apoptosis and cell cycle arrest, for example GSE increased G2/M phase arrest of the cell cycle leading to induction of apoptosis in a dose- and time-dependent manner in pancreatic cancer cell 28 . GSE also induces inhibition of cell growth in human bladder cancer cells by arresting cell cycle at G1 phase and inducing cell apoptosis 12 . In parallel, we observed that GSE treatment resulted in an increase in the expression of p53 and p21.…”

Section: Discussionmentioning

confidence: 99%

“…The consumer’s interest in GSE has been primarily due to its high content of antioxidants in the form of flavonoids, polyphenols and proanthocyanidins 10 , 11 . GSE has been shown to possess potent cardioprotective, hepatoprotective, antidiabetic, anti-mutagenic and anti-inflammatory properties 10 – 12 . Moreover, GSE has shown promising chemopreventive and anticancer effects in various cancer cells and in a wide variety of animal tumor models such as skin, colorectal, prostate and breast cancers 13 – 15 .…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of the grape seeds extract’s effect against chemically induced liver cancer: In vivo and in vitro analyses

Hamza

Heeba

Elwy

et al. 2018

Sci Rep

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The purpose of this study was to investigate the anti-cancer property of grape seed extract (GSE) during early stages of developing liver cancer using a two-stage carcinogenic model combining diethylnitrosamine (DEN) and 2-Acetyl Aminofluorene (2-AAF). Administration of GSE at doses 25, 50 and 100 mg/kg per day started at the beginning of promotion periods and continued for 14 weeks. GSE dramatically inhibited pre-neoplastic foci formation as well as significantly decreased the number and the area of placental glutathione-S-transferase in livers of DEN-2AAF-treated rats by approximately 4 & 10 fold deductions, respectively. GSE's effects were associated with induced apoptosis, reduced cell proliferation, decreased oxidative stress and down regulation of histone deacetylase activity and inflammation makers, such as cyclooxygenase 2, inducible nitric oxide synthase, nuclear factor-kappa B-p65 and p-phosphorylated tumor necrosis factor receptor expressions in liver. GSE treatment also decreased the viability of HepG2 cells and induced early and late apoptosis through activating caspase-3 and Bax. Furthermore, GSE induced G2/M and G1/S cell cycle arrest. The present study provides evidence that the GSE's anticancer effect is mediated through the inhibition of cell proliferation, induction of apoptosis, modulating oxidative damage and suppressing inflammatory response.Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death both in developed and under-developed countries 1 . Chronic infection with hepatitis B and C are the main causes of HCC 2 . Other factors that contribute to the formation of HCC include fatty liver disease, iron overload, alcoholism and exposure to environmental carcinogens 3 . One of the most common carcinogens is diethylnitrosamine (DEN), which is widely used in the surrounding of everyday life, in tobacco, smoke, processed food, gasoline, and cosmetics 4 .Chemoprevention of cancer especially by natural compounds is a promising strategy to protect against various stages of cancer development [5][6][7] . Total plant extracts have been of a particular interest mainly because of the synergistic effects of the cocktail of plant metabolites and their multiple points of intervention during chemoprevention 7,8 . The development of pre-neoplastic foci of altered hepatocytes (FAH) was exploited as short-term bioassays to assess the chemopreventive potential of natural products against cancer formation 9 . Thus, inhibiting or suppressing the development of pre-neoplastic FAH by natural products may lead to diminishing the subsequent progression to liver cancer. One particular plant product that has gained much attention is grape seed extract (GSE). Grapes (Vitis vinifera) are rich in polyphenols, with 60-70% of grape polyphenols being found in the seeds, which are available as a nutraceutical agent. The consumer's interest in GSE has been primarily due to its high content of antioxidants in the form of flavonoids, polyphenols and proanthocyanidins 10,11 . GSE has been shown to posses...

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“…GSP protects cells from damage by controlling the oxidative damage by reducing the tissue injury and maintains antioxidant status and reduces the release of pro-inflammatory mediators (Aysun et al, 2008). Moreover, (Liu et al, 2016) showed that GSPE increased the expression of Nuclear factor erythroid 2-related factor 2 (NRF2) and its target antioxidant genes superoxide dismutase and catalase and decreased the production of malondialdehyde and hydrogen peroxide in the liver of mice exposed to perfluorooctanoic acid. A significant up-regulation of Bax, IL-1β and NF-κβ gene expression levels with significant down-regulation of Bcl-2 gene were observed in stomach of ethanol-induced gastric ulcerative rats.…”

Section: Discussionmentioning

confidence: 99%

Proanthocyanidin ameliorates against ethanol -induced gastric mucosal erosion by attenuating inflammatory response, oxidative stress and apoptosis in rats

Obaia¹,

Elsenosi

Mahfouz

et al. 2020

Benha Veterinary Medical Journal

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Gastric ulcer is a common chronic disease in human digestive system. Massive alcohol drinking can lead to gastric ulcer. The gastroprotective effect and molecular mechanisms of Proanthocyanidin in a rat model of ethanol-induced gastric mucosal erosion were investigated. Thirty-five male rats were divided into five equal groups. Group 1 (Control normal): rats received no drugs. Group 2 (Early ulcer): rats received absolute ethanol (0.5 ml/100g) orally on empty stomach and sacrificed one hour later. Group 3 (Early ulcer + Proanthocyanidin protected): rats received proanthocyanidin orally at a dose of (300 mg/kg b. wt/day) for 3 weeks before ethanol administration then sacrificed after one hour. Group 4 (Late ulcer): rats received ethanol like group 2 and sacrificed after 21 days. Group 5 (Late ulcer + proanthocyanidin treated): rats first administered ethanol (0.5 ml/100g) and after one-hour proanthocyanidin was administered for 21 days. A significant increase in stomach L-MDA concentration with marked decrease in CAT activity and GSH concentration were observed in gastric erosion-induced rats. However, a significant depletion of gastric L-MDA level and marked increase in CAT activity and GSH concentration were observed after Proanthocyanidin treatment when compared to ulcerated rats. A significant up-regulation of gene expression level of BAX, NF-κB and IL-1β with downregulation of Bcl-2 gene were observed in stomach of gastric erosion-induced rats. However, a significant down regulation of BAX, NF-κB and IL-1β with up-regulation of Bcl-2 gene were observed after proanthocyanidin treatment. Conclusively, proanthocyanidin protects rat gastric mucosa against ethanol-induced gastric erosion via anti-inflammatory, anti-apoptotic and antioxidative mechanisms.

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Grape seed proanthocyanidin extract protects against perfluorooctanoic acid-induced hepatotoxicity by attenuating inflammatory response, oxidative stress and apoptosis in mice

Cited by 27 publications

References 47 publications

Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis

Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis

Molecular characterization of the grape seeds extract’s effect against chemically induced liver cancer: In vivo and in vitro analyses

Proanthocyanidin ameliorates against ethanol -induced gastric mucosal erosion by attenuating inflammatory response, oxidative stress and apoptosis in rats

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