Apocynin administration prevents the changes induced by a fructose-rich diet on rat liver metabolism and the antioxidant system

CASTRO MC; FRANCINI F; SCHINELLA G; CALDIZ CI; ZUBIRíA MG; GAGLIARDINO JJ; MASSA ML

CLINICAL SCIENCE (LONDON, ENGLAND : 1979)

PORTLAND PRESS LTD

Lugar: Londres; Año: 2012 vol. 123 p. 681 - 692

0143-5221

We studied the role of NAD(P)H oxidase in F (fructose)-induced hepatic OS (oxidative stress) and metabolic changes, and their prevention by apocynin co-administration. Wistar rats were fed for 21 days a) a control diet, b) a control diet plus 10% F in the drinking water, and c) a control and F diet plus apocynin in the drinking water. Glycemia, triglyceridemia, FAA (free fatty acids) and insulinemia were determined. In liver we measured a) NAD(P)H oxidase activity, gene and protein expression, b) protein carbonyl groups, reduced glutathione and TBARS, c) catalase, CuZn-superoxide dismutase and Mn-superoxide dismutase expression, d) liver glycogen and lipid content, e) GK (glucokinase), G-6-Pase (glucose-6-phosphatase) and G-6-P DH (glucose-6-phosphate dehydrogenase) activities, f) FAS (fatty acid synthase), GPAT (glycerol-3-phosphate acyltransferaseT), G-6-Pase and G-6-P DH, IL-ib (interleukin-1 beta), plasminogen activator inhibitor-1 and TNFá (tumor necrosis factor-alpha) gene expression, and g) IkBá (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) protein expression. F animals showed high serum triglyceride, FFA and insulin levels, high liver NAD(P)H oxidase activity/expression, increased OS markers, reduced antioxidant enzyme expression, and increased glycogen, triglyceride storage and GK, G-6-Pase and G-6-P DH activities. They also had high G-6-Pase, G-6-P DH, FAS, GPAT, TNFá and IL-1b gene expression, and decreased IkBá expression. Co-administration of apocynin to F rats prevented the development of most of these abnormalities. In conclusion, NAD(P)H oxidase plays a key role in F-induced hepatic OS production and probably also in the mechanism of liver steatosis, suggesting its potential usefulness for the prevention/treatment of Type 2 diabetes.