LETROZOLE SUPPRESSES HEPATIC OXIDATIVE STRESS AND AMELIORATES LIPID ACCUMULATION IN FRUCTOSE-EXPOSED WISTER RATS
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Date
2022-05-08
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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.