Effects of dark chocolate on NOX-2-generated oxidative stress in patients with non-alcoholic steatohepatitis.
Activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is considered a pathogenetic mechanism determining fibrosis and disease progression in non-alcoholic steatohepatitis (NASH). Polyphenols exert antioxidant action and inhibit NADPH oxidase in humans.



To analyse the effect of cocoa polyphenols on NADPH oxidase isoform 2 (NOX2) activation, oxidative stress and hepatocyte apoptosis in a population affected by NASH.



In a cross-sectional study comparing 19 NASH and 19 controls, oxidative stress, as assessed by serum NOX2 activity and F2-isoprostanes, and hepatocyte apoptosis, as assessed by serum cytokeratin-18 (CK-18) levels, were measured. Furthermore, the 19 NASH patients were randomly allocated in a crossover design to 40 g/day of dark chocolate (>85% cocoa) or 40 g/day of milk chocolate (<35% cocoa), for 2 weeks. sNOX2-dp, serum isoprostanes and CK-18 were assessed at baseline and after 2 weeks of chocolate intake.



Compared to controls, NASH patients had higher sNOX2-dp, serum isoprostanes and CK-18 levels. A significant difference for treatments was found in subjects with respect to sNOX2-dp, serum isoprostanes and serum CK-18. The pairwise comparisons showed that, compared to baseline, after 14 days of dark chocolate intake, a significant reduction in sNOX2-dp serum isoprostanes and CK-18 M30 was found. No change was observed after milk chocolate ingestion. A simple linear regression analysis showed that ∆ of sNOX2-dp was associated with ∆ of serum isoprostanes.



Cocoa polyphenols exert an antioxidant activity via NOX2 down-regulation in NASH patients.
Department of Internal Medicine and Medical Specialties, I Clinica Medica, Sapienza University of Rome, Rome, Italy.
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0000-0002-6542-6235
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Loffredo
Department of Internal Medicine and Medical Specialties, I Clinica Medica, Sapienza University of Rome, Rome, Italy.
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M
Del Ben
Department of Internal Medicine and Medical Specialties, I Clinica Medica, Sapienza University of Rome, Rome, Italy.
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L
Perri
Department of Internal Medicine and Medical Specialties, I Clinica Medica, Sapienza University of Rome, Rome, Italy.
R
R
Carnevale
Department of Internal Medicine and Medical Specialties, I Clinica Medica, Sapienza University of Rome, Rome, Italy.
C
C
Nocella
Department of Internal Medicine and Medical Specialties, I Clinica Medica, Sapienza University of Rome, Rome, Italy.
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E
Catasca
Department of Internal Medicine and Medical Specialties, I Clinica Medica, Sapienza University of Rome, Rome, Italy.
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F
Baratta
Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.
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F
Ceci
Department of Internal Medicine and Medical Specialties, I Clinica Medica, Sapienza University of Rome, Rome, Italy.
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L
Polimeni
Department of Surgery "Pietro Valdoni", University of Rome "La Sapienza", Rome, Italy.
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P
Gozzo
Department of Internal Medicine and Medical Specialties, I Clinica Medica, Sapienza University of Rome, Rome, Italy.
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Violi
Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy.
F
F
Angelico
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D000069956:Chocolate; D018592:Cross-Over Studies; D003430:Cross-Sectional Studies; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000178:diet therapy* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D059808:Polyphenols / Q000494:pharmacology
D000975:Antioxidants; D008562:Membrane Glycoproteins; D059808:Polyphenols; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases