Abstract
In the present study, we characterized the antioxidant and hepatoprotective mechanisms underlying of wild grape seed procyanidins (WGP) against oxidative stress damage in ethanol-treated HepG2 cell and Sprague-Dawley (SD)-rat models. In HepG2 cells, WGP not only diminished the ethanol (EtOH, 100 mM)-induced reactive oxygen species (ROS) formation and cytochrome P450 2E1 (CYP2E1) expression, but also renovated both the activity and expression of antioxidant enzymes including catalase, superoxide dismutase, and glutathione peroxidase. Additionally, to investigate the hepatoprotective effect of WGP, rats were orally administered 10 or 50 mg/kg WGP once daily for seven days prior to the single oral administration of EtOH (6 g/kg). The results show that WGP administration decreased the EtOH-induced augment of the levels of serum aspartate transaminase and alanine transaminase as well as serum alcohol and acetaldehyde. WGP treatment upregulated the activities and protein levels of hepatic alcohol dehydrogenase, aldehyde dehydrogenase, and antioxidant enzymes but downregulated the protein expression level of liver CYP2E1 in EtOH-treated rats. Moreover, the decreased phosphorylation levels of mitogen activated protein kinases (MAPKs) by ethanol were induced in both HepG2 cell and rat models. Overall, pretreatment of WGP displayed the protective activity against EtOH-mediated toxicity through the regulation of antioxidant enzymes and alcohol metabolism systems via MAPKs pathways.
Highlights
Different types of alcoholic beverages have played a vital part of the human diet since antiquity
The metabolic pathways involved in the hepatic transformation of ethanol are oxidation into acetaldehyde by alcohol dehydrogenase (ADH), microsomal ethanol oxidation system (MEOS), based on cytochromes P450 and, in particular, cytochrome P450 2E1 (CYP2E1), and to a much lesser extent by catalase (CAT) [2,3,4]
The ethanol concentration at ě100 mM produced a significant cell death in HepG2 cells; 100 mM ethanol was used for experiments to induce oxidative stress and CYP2E1 at 24 h (Figure 1A)
Summary
Different types of alcoholic beverages have played a vital part of the human diet since antiquity. A variety of phytochemicals has been studied to protect cells and tissues against oxidative stress by the regulation of antioxidant enzymes and CYP2E1 via the modulation of MAPK signaling pathways [25,26,27]. Various types of procyanidins from other species have been found to display radical scavenging antioxidant effects [31,32], little is known about antioxidant and hepatoprotective properties as well as the underlying mechanisms of WGP in the alcohol-induced hepatotoxicity model. In this present study, we examined the hepatoprotective and antioxidant mechanisms of WGP in alcohol-induced HepG2 cells and rats
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