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Drug Res (Stuttg). 2017 Feb;67(2):103-110. doi: 10.1055/s-0042-118386. Epub 2016 Nov 7.

Dietary Fructose-Induced Hepatic Injury in Male and Female Rats: Influence of Resveratrol.

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Faculty of Medicine, Department of Medical Pharmacology, Afyon Kocatepe University, Afyonkarahisar, Turkey.
Faculty of Veterinary, Department of Pathology, Ankara University, Ankara, Turkey.
Faculty of Medicine, Department of Medical Biochemistry, Afyon Kocatepe University, Afyonkarahisar, Turkey.
K.Ö. Science Faculty, Department of Biology, Karamanoglu Mehmetbey University, Karaman, Turkey.
Faculty of Pharmacy, Department of Pharmacology, Gazi University, Ankara, Turkey.


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.

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