Investigation of effects of caffeic acid phenethyl ester to plasma homocysteine,asymmetric dhymethyl arginine, nitric oxide and lipid profile in rats constituted experimental hyperthyroidism

Thyroid disorders are common endocrine disorders in humans and animals and are accompanied by important changes in haemodynamic, cardiac and renal function. Disturbances in the regulation of systemic arterial blood pressure are seen in hyperthyroid states in man and other animals Hyperthyroidism manifests a hyperdynamic circulation with increased cardiac output, increased heart rate and decreased peripheral resistance. Thyroid diseases may lead to endothelial dysfunction; however, the mechanism underlying the endothelial dysfunction in thyroid disease is not clear yet.Nitric oxide (NO) is produced through the transformation of L-arginine to L-citruline by a family of enzymes known as NO synthases (NOS). It is well known that NO is an important factor regulating vascular tone. Asymmetric Dimethyl Arginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase and causes local vasospasm and endothelial dysfunction by inhibiting local NO production. Hyperthyroidism is related with increased ADMA levels and decreased NO levels.Homocysteine is an intermediate compound of the metabolism of metionine, which is an essential sulphur-containing amino acid. Elevated plasma homocystein concentrations are associated with increased risk of vascular diseases.Propolis is one of the nature-based products, which is produced by honeybees in hives. The major compounds of propolis are caffeic acid esters which are also responsible for biologic activity of propolis and has been identified to show beneficial activities.This study was designed in rats with experimentally induced hyperthyroidism to investigate the protective effects of caffeic acid phenylethyl ester (CAPE) on may be formed endothelial dysfunction that based on thyroid hormons.We used fifty male Wistar albino (250-300 g) rats in this study. The experimental animals were divided into five groups as control, placebo, hyperthyroidism, CAPE and ?hyperthyroidism + CAPE?. Nothing was administered to the control group during four weeks. The animals in placebo group were administered intraperitonially 0,5 ml sterile physiological saline during 4 weeks. The animals in hyperthyroidism group were administered intraperitonially L-thyroxine 0,3 mg/kg in 0,5 ml. sterile physiological saline. The animals in CAPE group were administered intraperitonially CAPE at a dose of 10?g/kg in 0,5 ml sterile physiological saline per day during 4 weeks. The animals in ?hyperthyroidism + CAPE? group were administered 0,3 mg/kg L-thyroxine in 0,5 ml physiological saline and 10 mcg/kg CAPE. Plasma FT3, FT4, total cholesterol, HDL and Triglyceride levels were measured by autoanalyzer. Plasma LDL levels were calculated by the Freidewald equation. Plasma homocysteine levels were measured by HPLC. Plasma NO levels were measured by ELISA. statistically analysis was performed by SPSS 13.0 program, using one-way ANOVA test.Plasma fT3, fT4 concentrations were significantly increased in rats with hyperthyroidism compared to controls, placebo, CAPE and ?CAPE+HT? groups (p<0,001). Co-administration of CAPE with L thyroxine significantly decreased (p<0.001) the elevated fT3 and fT4 levels. Plasma homocysteine concentrations were significantly decreased in rats with hyperthyroidism compared to controls, placebo, CAPE and ?CAPE+HT? groups (p<0,001). Plasma homocystein levels obtained from ?CAPE+hyperthyroidism? group were significantly (p<0,001) higher compared to hyperthyroidism group.Plasma ADMA concentrations obtained from hyperthyroidism group were significantly higher compared to other groups. Plasma ADMA concentrations obtained from ?CAPE+hyperthyroidism? group were significantly higher compared to control, placebo and CAPE groups and significantly low compared to hyperthyroidism group. Plasma NO concentrations obtained from hyperthyroidism group were significantly low compared to control, placebo, CAPE and ?CAPE+hyperthyroidism? groups. Plasma NO concentrations obtained from ?CAPE+hyperthyroidism? group were significantly higher. Plasma total cholesterol, HDL, LDL and triglycerid levels obtained from hyperthyroidism group were significantly lower than other groups. Plasma total cholesterol, HDL, LDL and triglycerid levels obtained from ?CAPE+hyperthyroidism? group were significantly higher.In conclusion; CAPE may show a protective effect on endothelial damage by increasing plasma NO levels and decreasing ADMA levels, in hyperthyroidism induced rats.Key words: Hyperthyroidism, rat, asymmetric dimethyl arginine, nitric oxide, homocysteine.