Antioxidation Effect of Simvastatin in Aorta and Hippocampus: A Rabbit Model Fed High-Cholesterol Diet.

Guangyin Zhang,Li Peng,Yinzhi Xu,Ming Li,Cui Yang,Junping Zhang,Yanan Zhou

doi:10.1155/2016/6929306

Abstract

We show that hypercholesterolemia contributes to oxidative stress injury progression in brain and simvastatin counteracts the cholesterol-induced peroxidation injury in rabbit hippocampus, and we demonstrate for the first time that the simvastatin is a critical role in brain protection and identify HO-1 and other related antioxidant enzymes as molecular target for active redox compounds. Second, our experiments have pointed out an association between statin treatment and a decrease in the risk of having peroxidation damage of brain. The balance effects of simvastatin to ROS and antioxidants enzymes network are most probably due to improved SOD functional activity, increase in GSH-Px, increase in HO-1 expression, and decrease of MDA generation.

Highlights

Hypercholesterolemia is a major risk factor for age-related diseases such as atherosclerosis, obesity [1], and cardiovascular disease [2], and it has been known that the risk factors of various brain diseases play part in cardiovascular diseases such as dementia, including its most common form, Alzheimer’s disease (AD) [3]
It is well known that Heme oxygenase-1 (HO-1) plays a crucial role in the oxidative stress process during human atherosclerotic lesions; the HO-1 mRNA and protein expression can be found in various human organs including brain, liver, lung, heart, and kidney [21,22,23]
In a variety of those tissues, brown particles scattered and more immunoreactivity was observed in the Simvastatin treatment group (Figure 2(c)), while staining levels were moderate in HCD rabbit tissues (Figure 2(b)) and there were low levels of immunohistochemical staining in normal rabbit (Figure 2(a))

Summary

Introduction

Hypercholesterolemia is a major risk factor for age-related diseases such as atherosclerosis, obesity [1], and cardiovascular disease [2], and it has been known that the risk factors of various brain diseases play part in cardiovascular diseases such as dementia, including its most common form, Alzheimer’s disease (AD) [3]. The hippocampus is a major component of the brains of humans, which is exceptionally susceptible to oxidative stress that may be caused by hypercholesterolemia [4]. During the past few years, more evidences have accumulated that high-cholesterol level may increase the risk of developing dementia in the action of lipid metabolism-related enzymes [5] and oxidative stressrelated proteins [6]. Hypercholesterolemia is believed to cause oxidative stress by increasing the production of reactive oxygen species (ROS), and which play an important role in neuronal cell death, which is associated with many different neurodegenerative conditions, is a key event in a variety of inflammatory processes [8, 9]. It has been suggested that the accumulation of HO-1 proteins in the brain may be a protective response to oxidative stress [14]

Methods

Results

Conclusion