Thymol decreases apoptosis and carotid inflammation induced by hypercholesterolemia through a discount in oxidative stress

Objective: Atherosclerosis sclerosis is a chronic inflammatory disease that can lead to cardiovascular and cerebrovascular disorders that are generally along with hypercholesterolemia and oxidative stress. Various surveys have shown that thymol is a polyphenolic compound with anti-inflammatory and antioxidant properties. This study aimed to investigate the anti-inflammatory and antiapoptotic effects of thymol on carotid tissue of hypercholesterolemic rats. Materials and Methods: Forty male Wistar rats were randomly divided into 4 groups with 10 members each (n = 10): a control group with a normal diet (ND), a group with a high-cholesterol (2%) diet (HD), a group with a high-cholesterol diet combined with thymol (24 mg/kg HD + T), and a group with a thymol diet (T). After preparing serum from peripheral blood of rats, lipid measurements were obtained, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), by using a colorimetric method; the levels of oxidized LDL (OxLDL) were obtained through enzyme-linked immunosorbent assay (ELISA). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) antioxidant enzymes, as well as the concentrations of malondialdehyde (MDA) and serum total antioxidant capacity (TAC), were determined with the use of colorimetric methods. The protein expressions of Bcl2 and cleaved caspase 3 and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) in rat carotid tissue were determined by an immunoblotting method. Results: The rats fed with a high-cholesterol diet for 8 weeks increased TC and OxLDL in HD group compared with the ND group (P < 0.01; OxLDL HD vs ND (214.42 ± 17.46 vs 69.13 ± 9.92; P < 0.01); (229.39 ± 13.26 vs 67.89 ± 5-14 (215.58 ± 12.46 vs 229.35 ± 13.26; P < 0.05, OxLDL HD vs HD + T 105.53 ± 10.44; P < 0.01). Both of them were decreased with the intervention of thymol in the HD + T group compared with the HD group. The amount of phosphorylation of p38 (p-p38) and the protein expression of cleaved caspase 3 showed a significant increase in the HD group compared with the ND group (P < 0.01). In contrast, the expression of Bcl-2 in the high-cholesterol diet group decreased compared with the control group (P < 0.01). A comparison of the p-p38 and the protein expression of cleaved caspase 3 between the T + HD and the HD groups showed that in both cases, thymol caused a decrease (p<0.01), whereas Bcl-2 effected an increase (P < 0.05). Regarding the oxidant and antioxidant indices, thymol significantly decreased the MDA level and increased the total antioxidant content (P < 0.01). Conclusion: The results of this study indicate that thymol significantly decreases the expression of inflammatory and apoptotic proteins in carotid tissue. However, this decrease is probably not mediated by an effect on lipid metabolism because thymol decreases the total level of cholesterol but has no significant effect on the LDL-C level as the atherogenic index. In addition, thymol possibly exerts an antioxidant effect without the direct involvement of antioxidant enzymes