Dietary Fructose-Induced Hepatic Injury in Male and Female Rats: Influence of Resveratrol.
Purpose:Relatively little is known about gender-dependent susceptibility to hepatic injury induced by nutritional factors. In the current study, we investigated dietary fructose-induced hepatic degeneration and roles of endothelial nitric oxide synthase (eNOS), insulin receptor (IRβ) and substrate-1 (IRS-1) expressions in association with inflammatory markers in male and female rats. Moreover, we examined potential effect of resveratrol on fructose-induced changes.Methods:Male and female rats were divided into 4 groups as control, resveratrol, fructose and resveratrol plus fructose. All rats were fed with a standard diet with or without resveratrol (500 mg/kg). Fructose was given as 10% in drinking waterfor 24 weeks.Results:Long-term dietary fructose caused parenchymal degeneration and hyperemia in association with impaired eNOS mRNA/protein expressions in liver of male and female rats. This dietary intervention also led to increases in hepatic triglyceride content, TNFα and IL-1β levels in both genders. Gender-related differences to consequence of fructose consumption were not obvious. Resveratrol supplementation markedly attenuated hepatic degeneration, hyperemia and triglyceride content in association with reduced TNFα and IL-1β levels, but enhanced IRβ mRNA and IRS-1 protein, in male and female rats upon fructose feeding.Conclusion:Long-term dietary fructose causes hepatic degeneration possibly via a decrease in eNOS, but increase in TNFα and IL-1β, in both genders. Resveratrol supplementation improved fructose-induced hepatic injury.
Faculty of Medicine, Department of Medical Pharmacology, Afyon Kocatepe University, Afyonkarahisar, Turkey.
Mehmet Bilgehan
MB
Pektas
Faculty of Veterinary, Department of Pathology, Ankara University, Ankara, Turkey.
Gözde
G
Yücel
Faculty of Medicine, Department of Medical Biochemistry, Afyon Kocatepe University, Afyonkarahisar, Turkey.
Halit Buğra
HB
Koca
K.Ö. Science Faculty, Department of Biology, Karamanoglu Mehmetbey University, Karaman, Turkey.
Gökhan
G
Sadi
Faculty of Pharmacy, Department of Pharmacology, Gazi University, Ankara, Turkey.
Onur Gökhan
OG
Yıldırım
Faculty of Pharmacy, Department of Pharmacology, Gazi University, Ankara, Turkey.
Gözde
G
Öztürk
Faculty of Pharmacy, Department of Pharmacology, Gazi University, Ankara, Turkey.
Fatma
F
Akar
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D000070601:Diet, Carbohydrate Loading / Q000009:adverse effects*; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D066248:High Fructose Corn Syrup / Q000008:administration & dosage / Q000009:adverse effects; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced* / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D066248:High Fructose Corn Syrup; C000594089:IL1B protein, rat; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D053583:Interleukin-1beta; C526296:Irs1 protein, rat; D013267:Stilbenes; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D005632:Fructose; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D011972:Receptor, Insulin; D000077185:Resveratrol