Abstract

It has been shown that female rats are more responsive to dietary cholesterol challenge than male and also, hypercholesterolemia induction is easier in female rats. The present study was designed to investigate the effects of rutin (RT) and ascorbic acid (AA) combination on high cholesterol diet (HCD)-induced hepatic damage in female Wistar rats. Rats were randomly divided into four groups and fed by respective diets for 6 consecutive weeks. Hepatic enzymes activity and lipid profile were estimated in plasma samples. Nucleic acids, total proteins, malondialdehyde (MDA), glutathione (GSH), total cholesterol (TC) and triglycerides (TG) levels were measured in liver. Histopathological changes were observed in hepatic tissue. Enzymatic activity and lipid profile increased significantly in plasma of HCD fed rats, which was normalized in HCD+RT+AA group. In hepatic cells, total protein, nucleic acids and GSH levels were significantly decreased, while MDA, TC and TG levels were increased by HCD. These changes were significantly corrected in HCD+RT+AA group. The apparent protection was further confirmed by the histopathological screening. In conclusion, the study provides the presence of oxidative stress in hypercholesterolemic female rats and suggests beneficial effects of RT and AA combinations in combating the oxidative process in nonalcoholic fatty liver disease. Key words: Rutin, ascorbic acid, hypercholesterolemia, oxidative stress.

Highlights

  • Hypercholesterolemia is considered as one of the most familiar metabolic disorders and it is closely associated with obesity, diabetes mellitus, and several other metabolic syndromes (Farrell et al, 2008; Postic and Girard, 2008; Trauner et al, 2010)

  • Hypercholesterolemia was induced by following high cholesterol diet (HCD) supplementation for six consecutive weeks and that has conformed through the biochemical and histopathological changes

  • The present data of liver weights are in agreement with these reports as weights were significantly increased by HCD supplementation compared to controls

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Summary

Introduction

Hypercholesterolemia is considered as one of the most familiar metabolic disorders and it is closely associated with obesity, diabetes mellitus, and several other metabolic syndromes (Farrell et al, 2008; Postic and Girard, 2008; Trauner et al, 2010). Hypercholesterolemia can eventually lead to nonalcoholic fatty liver disease (NAFLD) by depositing the lipids and triglycerides in liver which is usually progress to cirrhosis or even hepato cellular carcinoma (Kim et al, 2012; Lee et al, 2007). Studies demonstrated that even short exposure to high cholesterol diet (HCD) is capable of inducing hypercholesterolemia and is significantly associated with oxidative stress (Tomofuji et al, 2006). Hypercholesterolemia was shown to impair oxidative stress biomarkers such as malondialdehyde (MDA) and superoxide dismutase (SOD) and known to boost ROS production via different mechanisms and increase lipid peroxidation. Studies demonstrated that oxidative stress associated with hypercholesterolemia have harmful effect on different organs heart, liver, and kidney. It is necessary to search for effective approaches to control hypercholesterolemia and the associated fatty liver complication. Antioxidant supplementations may effectively suppress oxidative stress, which seems to be a useful therapy (Yang et al, 2012)

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