Document Type : Original Article
Authors
1
Animal Physiology Unit, Department of Zoology, University of Ilorin, Ilorin, Nigeria -HOPE Cardiometabolic Research Team, University of Ilorin, Ilorin, Nigeria -Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, India
2
Animal Physiology Unit, Department of Zoology, University of Ilorin, Ilorin, Nigeria
3
HOPE Cardiometabolic Research Team, University of Ilorin, Ilorin, Nigeria-Cardiovascular Research Unit, Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
Abstract
An increase in sugar intake, especially fructose or fructose-containing sweeteners, poses a serious public health challenge globally. Unlike glucose, fructose metabolism results in generation of oxidative stress, which promotes hepatic lipid accumulation and consequently increases the risk of non-alcoholic fatty liver disease (NAFLD). Chronic administration of letrozole has been previously reported to decrease lipid peroxidation and increase antioxidants but its effect on fructose-induced lipid accumulation has not been investigated. Thus, the present study sought to investigate the ameliorative effect of letrozole on hepatic oxidative stress and lipid accumulation in high fructose-taking Wister rats. After 3-week of exposure, our results reveal that fructose intake increased hepatic total cholesterol (p< 0.01), triglycerides (p< 0.001) and free fatty acid (p< 0.001). Similarly, fructose increased hepatic malondialdehyde (MDA) (p< 0.001 vs. control) and decreased catalase and superoxide dismutase activities (p< 0.001 and p < 0.05 vs. control, respectively). Furthermore, our data show that high fructose intake elevated levels of uric acid and xanthine oxidase activity in the liver (p< 0.001 vs. control). However, letrozole treatment attenuated the hepatic lipid accumulation, reduced MDA level, and suppressed uric acid biosynthesis in high fructose-taking rats. Conclusively, this study has demonstrated that high fructose intake induces hepatic uric acid synthesis, generating oxidative stress and promoting hepatic lipid accumulation in male Wister rats, while administration of letrozole attenuates the fructose effects. Our findings, therefore, suggest the efficacy of letrozole in attenuating hepatic lipid accumulation, hence, lowering the risk of NAFLD associated with excessive fructose intake.
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