Miguel Arcanjo Areas

Os efeitos da metformina sobre a dispersão do intervalo QT e QTc de ratos diabéticos

BACKGROUND Several drugs can cause prolonged QT interval, as well as prolonged QT dispersion (QTd) in electrocardiographic (EKG) recordings. QTd may be a potentially sensitive marker of increased risk of cardiac arrhythmias and sudden cardiac death. Metformin is an effective antihyperglycemic agent used in the treatment of diabetes. However, studies have correlated dose-dependent effects of metformin on glycemia and cardiovascular risk markers. OBJECTIVE To evaluate the dose-response effects of metformin on QT and QTd of diabetic rats. METHODS Male Wistar rats were distributed in five groups: non-treated control (C), non-treated diabetics (D), diabetics treated with metmorfin at the doses of 3.5, 30 and 74 microg/kg/bw (DM 3.5, DM 30 and DM 74). Diabetes was induced by an alloxan injection (40 mg/kg, IV). EKG was recorded (days 1, 15 and 30) using four electrodes inserted into the subcutaneous layer of the paws. Both RR and QT intervals were measured, and then corrected QT and QT dispersion values were calculated. RESULTS The DM 3.5 and DM 30 groups showed a significant reduction of glycemia (p< 0.05) when compared with the high dose (DM 74). Rats of the DM 74 group presented prolonged QTc, QTd and QTcd intervals, whereas rats of the DM 3.5 and DM 30 groups presented less prolonged intervals. CONCLUSION Metformin at high doses provided greater dispersion of the QT interval probably because of the increased ventricular repolarization inhomogeneity, whereas at low doses decreased QT intervals were observed in diabetic rats.BACKGROUND: Several drugs can cause prolonged QT interval, as well as prolonged QT dispersion (QTd) in electrocardiographic (EKG) recordings. QTd may be a potentially sensitive marker of increased risk of cardiac arrhythmias and sudden cardiac death. Metformin is an effective antihyperglycemic agent used in the treatment of diabetes. However, studies have correlated dose-dependent effects of metformin on glycemia and cardiovascular risk markers. OBJECTIVE: To evaluate the dose-response effects of metformin on QT and QTd of diabetic rats. METHODS: Male Wistar rats were distributed in five groups: non-treated control (C), non-treated diabetics (D), diabetics treated with metmorfin at the doses of 3.5, 30 and 74 µg/kg/bw (DM 3.5, DM 30 and DM 74). Diabetes was induced by an alloxan injection (40 mg/kg, IV). EKG was recorded (days 1, 15 and 30) using four electrodes inserted into the subcutaneous layer of the paws. Both RR and QT intervals were measured, and then corrected QT and QT dispersion values were calculated. RESULTS: The DM 3.5 and DM 30 groups showed a significant reduction of glycemia (p< 0.05) when compared with the high dose (DM 74). Rats of the DM 74 group presented prolonged QTc, QTd and QTcd intervals, whereas rats of the DM 3.5 and DM 30 groups presented less prolonged intervals. CONCLUSION: Metformin at high doses provided greater dispersion of the QT interval probably because of the increased ventricular repolarization inhomogeneity, whereas at low doses decreased QT intervals were observed in diabetic rats.

Melatonin reduces oxidative stress and cardiovascular changes induced by stanozolol in rats exposed to swimming exercise.

OBJECTIVE Anabolic-androgenic steroids (AAS) are nominated for clinical use to promote protein synthesis in many therapeutic conditions. However, the indiscriminate use of AAS is related to hazardous cardiac disturbances and oxidative stress. We designed a study to investigate whether prolonged treatment with high doses of stanozolol modifies the activities of some antioxidant enzymes in the heart in sedentary and trained rats and whether this treatment causes alterations of cardiovascular parameters. In addition, the effectiveness of melatonin as an antioxidant and as a modulator of the cardiovascular side effects of stanozolol (STA) treatment was analyzed. MATERIALS AND METHODS Thirty male Wistar rats were divided into the following six groups: sedentary (S), stanozolol sedentary (SS), stanozolol-melatonin sedentary (SMS), trained (T), stanozolol trained (ST) and stanozolol-melatonin trained (SMT). The stanozolol-treatment rats received 5 mg.kg(-1) by subcutaneous injection before each exercise session (5 d.wk(-1), i.e., 25 mg.kg(-1).wk(-1)), while control groups received only saline solution injection. The melatonin-treatment groups received intraperitoneal injections of melatonin (10 mg.kg(-1)), 5 d.wk(-1) for 6 wk. Electrocardiography, blood pressure and antioxidant enzyme activity measurements were performed at the end of the experimental period for cardiac function and molecular assessment. RESULTS This is the first time that the in vivo effects of melatonin treatment on stanozolol-induced cardiovascular side effects have been studied. Stanozolol induced bradycardia and significantly increased cardiac superoxide dismutase and catalase activities. Trained stanozolol-treated rats experienced an increase in blood pressure and relative heart weight, and they developed left cardiac axis deviation. Although melatonin did not prevent cardiac hypertrophy in exercised stanozolol-treated animals, it maintained blood pressure and cardiac catalase activity, and it prevented stanozolol-induced cardiac electrical axis deviation. CONCLUSION In conclusion, under our experimental conditions, chronic stanozolol administration induced mild cardiovascular side effects that were partly attenuated by melatonin treatment. However, these results showed that the combination of melatonin and exercise could minimize the stanozolol side effects in the cardiovascular system.

Suramin attenuates dystrophin-deficient cardiomyopathy in the mdx mouse model of duchenne muscular dystrophy.

Introduction: The purpose of this study was to determine the effects of suramin, an antifibrotic agent, on cardiac function and remodeling in mdx mice. Methods: mdx mice (8 months old) received intraperitoneal injections of suramin twice a week for 3 months. Control mdx mice (8 months old) were injected with saline. Results: Suramin improved the electrocardiography profile with the main corrections seen in S‐ to R‐wave ratio, PR interval, and Q amplitude, and a significant decrease in the cardiomyopathy index. Suramin decreased myocardial fibrosis, inflammation, and myonecrosis. Conclusions: These findings suggest that suramin may be a new adjunctive therapy to help improve cardiomyopathy in DMD. Muscle Nerve 48: 911–919, 2013

Deltamethrin and Permethrin in the liver and heart of Wistar rats submitted to oral subchronic exposure

For 28 days male Wistar rats were submitted to oral exposure with 1/10 of the LD50 value of permethrin (PMT) or deltamethrin (DMT). The aim of this study was to determine the residues of PMT and DMT in the liver and heart of the rats at the end of the exposure period, as well as to evaluate the effect of ingesting pectin and cellulose via the diet. The analytes were extracted with acetonitrile and the extracts were cleaned up by solid phase extraction with florisil before GC-ECD (gas chromatography coupled with an electron-capture detector) analysis. For PMT, the limits of quantitation (LOQ) were 1.0 and 0.2 µg g-1 and for DMT 0.9 and 0.2 µg g-1 for liver and heart, respectively. No PMT or DMT residues were verified above the LOQ of the method in either the liver or heart of the exposed animals

Long-term Leucine Supplementation Improves Metabolic But Not Molecular Responses in the Skeletal Muscle of Trained Rats Submitted to Exhaustive Exercise

Aim: Although there is some evidence of an ergogenic effect of leucine supplementation on acute response to exercise, there is a paucity of information on whether long-term leucine supplementation influences the adaptive response to chronic endurance training and performance. The main aim of our study was to assess the role of long-term leucine supplementation on molecular and metabolic response in skeletal muscle of trained rats after an exhaustion test. Methods: Twenty-four male Wistar rats were randomly allocated into 4 groups. Two of them (control and trained groups) received a balanced control diet (18% protein) and the other 2 (control leucine and trained leucine groups) received a leucine-rich diet (15% protein with 3% leucine) for 6 weeks. The trained groups were submitted to 1 hour of swimming exercise, 5 d/wk for 6 weeks. Three days after the exercise training period, trained groups were submitted to swimming exercise until exhaustion and muscle metabolic and molecular parameters were assessed. Results: Endurance training increased citrate synthase activity significantly, whereas exercise until exhaustion increased cytokine levels and led to a lack of activation of phosphorylation of the signaling intermediates assessed. Long-term leucine supplementation enhanced muscle glycogen level in trained rats and citrate synthase activity in sedentary ones. However, it failed to enhance endurance performance of trained rats submitted to an exhaustion test and did not prevent exercise-induced reduction in Akt and mTOR activation. Conclusion: Long-term leucine supplementation can enhance citrate synthase activity by itself in sedentary individuals and glycogen content when combined with exercise; however, it does not improve endurance performance or prevent Akt and mTOR exercise-induced inhibition.

Long‐term leucine supplementation aggravates prolonged strenuous exercise‐induced cardiovascular changes in trained rats

What is the central question of this study? Can long‐term leucine supplementation prevent prolonged strenuous endurance exercise induced cardiac injury? What is the main finding and its importance? Prolonged endurance exercise does not seem to exceed cardiac energetic capacity, hence it does not represent an energy threat to this organ, at least in trained subjects. However, it may induce, in susceptible individuals, a state of cardiac electrical instability, which has been associated with ventricular arrhythmias and sudden cardiac death. This situation might be worsened when combined with leucine supplementation, which leads to increased blood pressure and cardiac injury. Leucine supplementation failed to prevent cardiac fatigue symptoms and may aggravate prolonged strenuous exercise‐induced cardiovascular disturbances in trained rats.