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

Abstract

<jats:p>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).</jats:p>

Fructose-enriched diet induces inflammation and reduces antioxidative defense in visceral adipose tissue of young female rats

“…Similarly, fructose-related activation of cardiac NF-κB was previously reported [47], but in contrast to our results obtained in females, it was not observed in the VAT of young male rats [48]. Several researchers reported elevated IL-1β and TNFα in the liver [49] and plasma [50][51][52] after fructose feeding. In the study of Hsieh [53], dietary fructose was shown to elicit TNFα concentrations in the adipose tissue of male rats.…”

“…A number of studies have demonstrated decreased expression or activity of antioxidative enzymes after fructose consumption and a concomitant presence of oxidative stress [49,51,65]. The oxidative environment evoked by fructose overconsumption might be an explanation for decreased glucocorticoid receptor's hormone-binding capacity and affinity observed in our previous study [44].…”

“…The presence of oxidative stress is commonly accompanied by increased levels of pro-inflammatory cytokines including IL-1β and TNFα along with disturbed insulin signaling [49][50][51][52]. There is a complex relationship between inflammation and oxidative stress in obesity and related disorders that seems to be revolving in the vicious cycle; hence, the time course has not been established yet.…”

Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction

“…Protein carbonyl and GSH liver contents were determined as described elsewhere [22]. Briefly, both components were spectrophotometrically measured (at 366 nm for protein carbonyl groups and 414 nm for GSH) and results were expressed in nmol of carbonyl residues per mg of protein based on the molar extinction coefficient of 21,000 M −1  cm −1 .…”

“…Total liver RNA was isolated using the TRIzol Reagent (Gibco-BRL, Rockville, MD, USA) as previously described [22]. The integrity and quality of the isolated RNA were checked by agarose-formaldehyde gel electrophoresis and by measuring the 260/280 nm absorbance ratio.…”