Attenuation of Oxidative Stress in Plasma and Tissues of Rats with Experimentally Induced Hyperthyroidism by Caffeic Acid Phenylethyl Ester

Abstract

Increased oxidative stress with high free radical generation has been described previously in animal models of hyperthyroidism. The present study was designed to investigate the protective effects of caffeic acid phenylethyl ester (CAPE) on oxidative damage in rats with experimentally induced hyperthyroidism. The study was conducted on 32 male Sprague-Dawley rats. The experimental animals were divided into four groups (control, CAPE alone, hyperthyroidism, and hyperthyroidism + CAPE). Hyperthyroidism was induced by intraperitoneal administration of 0.3 mg/kg/day  -thyroxine for 4 weeks. CAPE (10 µ g/kg) was administered intraperitoneally for 4 weeks. At the end of the experimental period, blood samples and various organs (liver, heart and brain) of rats were taken for the determination of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), oxidized glutathione, vitamin C and superoxide dismutase (SOD) levels and concentrations of triiodothyronine (T3), thyroxine (T4) and thyroxine-stimulating hormone (TSH). Our results indicate that TBARS, oxidized glutathione, SOD levels and concentrations of T3 and T4 were higher in plasma and tissues of the hyperthyroid group compared to controls. Vitamin C, GSH and TSH levels were decreased significantly in the hyperthyroid group when compared to the control group. CAPE treatment decreased the elevated TBARS, SOD, T3 and T4 levels and increased the lowered GSH, vitamin C and TSH levels to control levels in rats with hyperthyroidism. In conclusion, our results indicate that CAPE is beneficial as a protective agent against oxidative stress induced by hyperthyroidism in rats. The protection is probably due to multiple mechanisms involving free radical scavenger properties, attenuating lipid peroxidation and increasing the antioxidant status.The term hyperthyroidism is used for the overproduction of thyroid hormones from the thyroid gland and an excess of these hormones in the blood. Thyroid hormones accelerate the basal metabolic rate and oxidative metabolism by induction of specific mitochondrial enzymes [1], and hyperthyroidism accelerates reactive oxygen species (ROS) production and induces changes in the antioxidant protective systems of various tissues [2]. It is well documented that thyroid hormone administration to experimental animals induces oxidative stress in some tissues [3,4]. The cellular system is equipped with both enzymatic (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) and non-enzymatic (glutathione and vitamins C, E and A) defences to counteract the ROS [5].In fact, enhancement in lipid peroxidation indicators occurs in liver, heart, muscle and testis [6,7] from hyperthyroid rats. In addition to lipid peroxidation, hyperthyroidism also promotes hepatic and heart protein oxidation [8,9]. These effects seem to be primarily determined through increased mitochondrial production of ROS [10] likely because of a greater mitochondrial content of the autoxidizable electron carriers [11]. Lipid pero...

Oxidative Stress and Antioxidant Status in Hypo- and Hyperthyroidism

“…In our study, the increased levels of protein-bound carbonyls in serum of L-thyroxinetreated rats is in agreement with the earlier reports [150,151] suggesting the role of free radicals in the pathogenesis, which demand the need for studies assessing the therapeutic role of antioxidants in hyperthyroidism.…”

Efeito da coenzima Q10 nos danos oxidativos induzidos pela L-tiroxina no músculo sóleo de ratos

“…As caixas plásticas, com dimensões (CxLxA) 41x34x16 cm, foram armazenadas sob temperatura controlada de aproximadamente 22ºC. Os animais receberam alimento e água ad libitum e foram divididos em quatro grupos de seis animais de acordo com cada tratamento, por 30 dias: Grupo 1 (G1, controle), recebeu apenas o veículo da L-tiroxina e óleo de milho (via intraperitoneal); Grupo 2 (G2), recebeu o veículo da L-tiroxina e coenzima Q10 (10 mg/kg de peso vivo, de acordo com El-Sheikh et al 21 ) dissolvida em óleo de milho (via oral por gavagem); Grupo 3 (G3), recebeu a L-tiroxina (0,3 mg/kg de peso vivo 22 ) dissolvida em NaOH 0,01 M, e posteriormente diluída 10 vezes em soro fisiológico estéril; Grupo 4 (G4), recebeu a coenzima Q10 (via oral) e L-tiroxina (via intraperitoneal).…”

“…O tratamento com a L-tiroxina induziu o estresse oxidativo no homogenato do mús-culo sóleo de ratos como indicado pela diminuição nas concentrações de GSH e um aumento nas concentrações de GSSG no homogenato analisado. Essas alterações encontradas no ciclo redox da glutationa no presente estudo condizem com os encontrados por Seymen et al 10 no músculo esquelético e Mohamadin et al 22 no músculo cardíaco de ratos, os quais demonstraram diminuição significativa da GSH e aumento da GSSG em animais tratados com L-tiroxina. Em nosso estudo, o tratamento dos animais com a CoQ10, reestabeleceu as concentrações de GSH e GSSG, indicando efeito antioxidante da substância.…”

Tri-iodothyronine treatment differently affects liver metabolic response and oxidative stress in sedentary and trained rats

“…Hyperthyroid state-linked liver oxidative damage can be attenuated by strengthening antioxidant status, as demonstrated by the observation that the administration of vitamin E (Venditti et al 1999a) and caffeic acid phenylethyl ester (Mohamadin et al 2007) protects against lipid peroxidation in hyperthyroid liver.…”