Abstract
Oxidative stress is one of the key factors in the pathophysiology of liver disease. The present study aimed to evaluate the potential impact of two antioxidants, namely coenzyme Q10 (CoQ10) and silymarin, on carbon tetrachloride (CCl4)-induced oxidative stress and hepatic damage in ovariectomized rats. Female Long Evans rats were divided into six groups (n = 6): control, CCl4, CCl4 + CoQ10 (200 mg/kg), CCl4 + silymarin (140 mg/kg), Control + CoQ10, and Control + silymarin. Plasma and tissues from liver and kidney were analyzed for oxidative stress parameters and antioxidant enzyme activities using biochemical assays. Infiltration of inflammatory cells and fibrosis were assessed by histological staining of tissue sections. Both CoQ10 and silymarin significantly lowered serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels that were detected to be higher in CCl4 rats compared to controls. Significant reduction in CCl4-induced elevated levels of oxidative stress markers malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) was observed with both antioxidants. However, in control rats, CoQ10 and silymarin did not produce a significant effect. Histological analysis revealed that CCl4 markedly increased the level of inflammatory cells infiltration and fibrosis in liver and kidney tissues, but this was significantly reduced in CCl4 + CoQ10 and CCl4 + silymarin groups. Taken together, our results suggest that CoQ10 and silymarin can protect the liver against oxidative damage through improved antioxidant enzyme activities and reduced lipid peroxidation. Thus, supplementation of the aforementioned antioxidants may be useful as a therapeutic intervention to protect liver health in chronic liver diseases.
Highlights
During the entire experimentation period, all rats were weighed routinely, and we found no substantial changes in body weight between the different groups except the rats that received only CCl4 (Figure 1a)
We further observed that administration of coenzyme Q10 (CoQ10) or silymarin had no relation with weight loss or weight gain compared to control rats
Week of treatment, there was marked reduction in body weight in CCl4-treat compared to other groups
Summary
Excessive production of free radicals, such as superoxide, hydroxyl, hydrogen peroxide, and nitric oxide radicals in living beings causes homeostatic imbalance and oxidative stress leading to damage to biological molecules such as proteins, nucleic acids, and membrane lipids [1]. Carbon tetrachloride (CCl4 ) is a well-known hepatotoxin used for studying hepatotoxicity leading to pathogenesis of hepatic damage in animal models [5]. Metabolic products of CCl4 lead to the generation of trichloromethyl and proxy chloromethyl free radicals, causing an imbalance between reactive oxygen species (ROS) and antioxidants and resulting in liver damage and necrosis. Ovariectomized rat models are often used in clinical studies to overcome the antioxidant effects of estrogen, an ovarian hormone that can inhibit lipid peroxidation and reduce lipoprotein oxidation and superoxide anion production [1,7]. Estrogen plays a protective role through mechanisms such as inhibition of fibrogenesis, cellular senescence, increase in innate immunity, and protection of mitochondrial structure and function [8]
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