Polyunsaturated fatty acids balance affects platelet NOX2 activity in patients with liver cirrhosis.
BACKGROUND
NADPH-oxidase-2 up-regulation has been suggested in liver damage perpetuation via an oxidative stress-mediated mechanism. n-6/n-3 polyunsaturated fatty acids ratio derangement has been reported in liver disease.


OBJECTIVE
To explore polyunsaturated fatty acids balance and its interplay with platelet oxidative stress in liver cirrhosis.


METHODS
A cross-sectional study in 51 cirrhotic patients and sex- and age-matched controls was performed. Serum polyunsaturated fatty acids and oxidative stress markers (urinary isoprostanes and serum soluble NADPH-oxidase-2-derived peptide) were measured. The effect on platelet oxidative stress of n-6/n-3 polyunsaturated fatty acids ratio in vitro and in vivo (1-week supplementation with 3g/daily n-3-polyunsaturated fatty acids) was tested.


RESULTS
Compared to controls, cirrhotic patients had significantly higher n-6/n-3 polyunsaturated fatty acids ratio. n-6/n-3 polyunsaturated fatty acids ratio correlated significantly with disease severity and oxidative stress markers. In vitro experiments showed that in Child-Pugh C patients' platelets incubation with low n-6/n-3 polyunsaturated fatty acids ratio resulted in dose-dependent decrease of radical oxigen species (-39%), isoprostanes (-25%) and NADPH-oxidase-2 regulation (-51%). n-3 polyunsaturated fatty acids supplemented patients showed significant oxidative stress indexes reduction.


CONCLUSIONS
In cirrhosis, n-6/n-3 polyunsaturated fatty acids imbalance up-regulates platelet NADPH-oxidase-2 with ensuing oxidative stress. Further study to evaluate if n-3 supplementation may reduce disease progression is warranted.
First Medical Clinic (Department of Internal Medicine and Medical Specialties), Sapienza-University of Rome, Italy.
Stefania
S
Basili
First Medical Clinic (Department of Internal Medicine and Medical Specialties), Sapienza-University of Rome, Italy.
Valeria
V
Raparelli
First Medical Clinic (Department of Internal Medicine and Medical Specialties), Sapienza-University of Rome, Italy.
Laura
L
Napoleone
First Medical Clinic (Department of Internal Medicine and Medical Specialties), Sapienza-University of Rome, Italy.
Maria
M
Del Ben
Gastroenterology Unit (Department of Clinical Medicine), Sapienza-University of Rome, Italy.
Manuela
M
Merli
Gastroenterology Unit (Department of Clinical Medicine), Sapienza-University of Rome, Italy.
Oliviero
O
Riggio
First Medical Clinic (Department of Internal Medicine and Medical Specialties), Sapienza-University of Rome, Italy.
Cristina
C
Nocella
First Medical Clinic (Department of Internal Medicine and Medical Specialties), Sapienza-University of Rome, Italy.
Roberto
R
Carnevale
First Medical Clinic (Department of Internal Medicine and Medical Specialties), Sapienza-University of Rome, Italy.
Pasquale
P
Pignatelli
First Medical Clinic (Department of Internal Medicine and Medical Specialties), Sapienza-University of Rome, Italy. Electronic address: francesco.violi@uniroma1.it.
Francesco
F
Violi
D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000201:enzymology*; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D015525:Fatty Acids, Omega-3 / Q000097:blood*; D043371:Fatty Acids, Omega-6 / Q000097:blood*; D005260:Female; D006801:Humans; D028421:Isoprostanes / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood* / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D010455:Peptides / Q000097:blood; D017382:Reactive Oxygen Species / Q000378:metabolism; D012720:Severity of Illness Index
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D028421:Isoprostanes; D008562:Membrane Glycoproteins; D010455:Peptides; D017382:Reactive Oxygen Species; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
Isoprostanes; Liver cirrhosis; NADPH oxidase; Oxidative stress; Polyunsaturated fatty acids