RESUMO
Type 2 diabetes mellitus (T2DM) increases the risk of cardiovascular disease, especially myocardial injury. Due to their hypoglycemic effects, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are efficiently used for T2DM management. GLP-1RAs also have anti-inflammatory and antioxidative effects and can improve cardiac function. The aim of this study was to investigate the cardioprotective effects of liraglutide, a GLP-1RA, on isoprenaline-induced myocardial injury in rats. The study included four groups of animals. They were pretreated with saline for 10 days + saline on days 9 and 10 (control), saline for 10 days + isoprenaline on days 9 and 10 (isoprenaline group), liraglutide for 10 days + saline on days 9 and 10 (liraglutide group), and liraglutide for 10 days, and on days 9 and 10 isoprenaline was administered. This study evaluated ECG, myocardial injury markers, oxidative stress markers, and pathohistological changes. The results showed that liraglutide mitigated the isoprenaline-induced cardiac dysfunction recorded by ECG. Liraglutide reduced serum markers of myocardial injury such as high-sensitive troponin I, aspartate aminotransferase, alanine aminotransferase, reduced thiobarbituric acid reactive substances, increased catalase and superoxide dismutase activity, increased reduced glutathione level, and improved lipid profile. Liraglutide induced antioxidative protection and alleviated isoprenaline-induced myocardial injury.
Assuntos
Diabetes Mellitus Tipo 2 , Traumatismos Cardíacos , Ratos , Animais , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Isoproterenol/toxicidade , Hipoglicemiantes/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Traumatismos Cardíacos/induzido quimicamente , Traumatismos Cardíacos/prevenção & controle , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistasRESUMO
Background: Isoprenaline (ISO), a synthetic catecholamine and a ß-adrenoceptor agonist, is widely used to develop an experimental model of myocardial injury (MI) in rats. The leading hypothesis for ISO-induced MI in rats is that it results from catecholamine overstimulation, oxidative stress, inflammatory responses, and development of cardiomyopathy during ISO administration. Folic acid (FA) reduces oxidative stress, improves endothelial function and prevents apoptosis, thereby contributing to cardiovascular protection. This study aimed to investigate the potentially protective effect of FA pretreatment on ISO-induced MI in rats. Methods: For 7 days, adult male Wistar albino rats were pretreated with 5 mg/kg/day of FA. On the sixth and seventh days, MI in rats was induced by administering 85 mg/kg/day of ISO. Prooxidant markers in plasma samples, antioxidant capacity in erythrocyte lysates, cardiac damage markers, lipid profile, electrocardiography (ECG) and histopathological analysis were evaluated. Results: FA pretreatment significantly alleviated changes induced by ISO; it decreased the homocysteine and high-sensitivity troponin I level. FA moderately decreased the reactive oxygen species (ROS) levels (superoxide anion radical, hydrogen peroxide and thiobarbituric acid reactive substances) and improved the antioxidant activities of catalase, superoxide dismutase and reduced glutathione. ISO reduced the nitrite level and FA significantly alleviated this change. Conclusion: It can be concluded that FA, as a mild antioxidant, could be an appropriate cardioprotective substance in the rat model of ISO-induced MI.