Apocynin administration prevents the changes induced by a fructose-rich diet on rat liver metabolism and the antioxidant system.
In the present study, we investigated the role of NADPH oxidase in F (fructose)-rich-diet-induced hepatic OS (oxidative stress) and metabolic changes, and their prevention by apocynin co-administration. Wistar rats were fed for 21 days on (i) a control diet, (ii) a control diet plus 10% F in the drinking water, (iii) a control diet with apocynin in the drinking water (CA) and (iv) F plus apocynin in the drinking water (FA). Glycaemia, triglyceridaemia, NEFAs (non-esterified fatty acids) and insulinaemia were determined. In the liver, we measured (i) NADPH oxidase activity, and gene and protein expression; (ii) protein carbonyl groups, GSH and TBARSs (thiobarbituric acid-reactive substances); (iii) catalase, CuZn-SOD (superoxide dismutase) and Mn-SOD expression; (iv) liver glycogen and lipid content; (v) GK (glucokinase), G6Pase (glucose-6-phosphatase) and G6PDH (glucose-6-phosphate dehydrogenase) activities; (vi) FAS (fatty acid synthase), GPAT (glycerol-3-phosphate acyltransferase), G6Pase and G6PDH, IL-1β (interleukin-1β), PAI-1 (plasminogen-activator inhibitor-1) and TNFα (tumour necrosis factor α) gene expression; and (vii) IκBα (inhibitor of nuclear factor κB α) protein expression. F-fed animals had high serum TAG (triacylglycerol), NEFA and insulin levels, high liver NADPH oxidase activity/expression, increased OS markers, reduced antioxidant enzyme expression, and increased glycogen, TAG storage and GK, G6Pase and G6PDH activities. They also had high G6Pase, G6PDH, FAS, GPAT, TNFα and IL-1β gene expression and decreased IκBα expression. Co-administration of apocynin to F-fed rats prevented the development of most of these abnormalities. In conclusion, NADPH 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 T2DM (Type 2 diabetes mellitus).
CENEXA - Centro de Endocrinología Experimental y Aplicada, UNLP-CONICET LA PLATA, Centro Colaborador OPS/OMS para Diabetes, Argentina.
María Cecilia
MC
Castro
Flavio
F
Francini
Guillermo
G
Schinella
Claudia Inés
CI
Caldiz
María Guillermina
MG
Zubiría
Juan José
JJ
Gagliardino
María Laura
ML
Massa
D000098:Acetophenones / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005632:Fructose / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D000098:Acetophenones; D001786:Blood Glucose; D017931:DNA Primers; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D005632:Fructose; C056165:acetovanillone; D002374:Catalase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D005978:Glutathione