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

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.

Figure 1

Simvastatin therapy enhanced HO-1 mRNA in hippocampus and also in aorta. (a) HO-1 mRNA expression in aorta; (b) levels of HO-1 mRNA in rabbit hippocampus homogenate. Data are presented as mean ± SD (n = 8). ## means P < 0.01 indicates significant change from control groups, at P < 0.01 using ANOVA followed by LSD as a one-ANOVA test.

Figure 2

Representative immunohistochemical staining (100x) analysis of rabbit tissues exposed to specific anti-HO-1. (a) Weak staining on the sections of hippocampus from control rabbit. (b) A fewer brown particles in HCD rabbit sections. (c) More brown particles scattered and strong positive staining was observed in the Simvastatin treatment group. (d) HO-1 positive area (%) shown; data are expressed as mean ± SD (n = 8), and there was no significant difference in staining degree between each group.

Figure 3

H&E staining of hippocampal sections isolated from rabbit hippocampi. Pyramidal neurons in hippocampus showed no change in H&E staining in the control group. In contrast, atherogenic diet induced a fraction of pyramidal neurons that exhibited morphologic features of necrosis, and there had been fewer necrotic pyramidal neurons than matched sections from Simvastatin treatment group rabbits.

Figure 4

Analysis of biochemical measurements in each group of rabbits; Simvastatin enhanced the antioxidant status in hippocampus and aorta and reduced oxidative stress. (a) Effects of Simvastatin on MDA in serum. (b) Levels of MDA in hippocampal tissues; (c) SOD in serum; (d) levels of SOD in hippocampal homogenate. (e) Activity of GSH-Px in rabbit hippocampus. (f) Activity of iNOS showed in hippocampal tissues. Data are presented as mean ± SD (n = 8). ∗∗ and ## indicate significant change from control and HCD groups, respectively, at P < 0.01; # means P < 0.05 compared to the HCD group using ANOVA followed by LSD as a one-ANOVA test.