Banca de QUALIFICAÇÃO: MARCELLE MARIANA SALES DE FRANCA

EFFECTS OF TREATMENT WITH L-CARNITINE IN RATS WITH CARDIOVASCULAR AUTONOMIC DIABETIC NEUROPATHY WHETHER OR NOT SUBMITTED TO PHYSICAL EXERCISE: A HISTOLOGICAL, BIOCHEMICAL AND IMMUNOHISTOCHEMICAL ANALYSIS

Alpha Lipoic Acid; Cardiac neuropathy; Histology; Physical Activity; Insulin.

Diabetic neuropathy is the most common complication of diabetes. One of its most prevalent clinical forms is autonomic neuropathy, which affects the innervation of various systems, including the cardiovascular system. Cardiovascular Autonomic Diabetic Neuropathy (CADN) has a high mortality rate. Among its symptoms are postural hypotension and cardiac arrhythmia, among others. Treatment focuses on symptom alleviation, as there is no standardized protocol for the treatment of the disease. In Brazil, Alpha-Lipoic Acid is recommended, along with physical exercise, which is already used for diabetes management. An alternative treatment involves L-carnitine. However, there are no reports on the effects of these substances on CADN. Therefore, the aim of this project is to compare the efficacy of L-carnitine and alpha-lipoic acid in the treatment of CADN in experimental groups subjected to physical exercise or not. Forty male Wistar rats, aged 90 days, were used. These were divided into 8 experimental groups: sedentary non-diabetic (RS), trained non-diabetic (RTC), trained diabetic (RTD), trained diabetic with insulin (RTDI), trained diabetic with L-carnitine (RTDLC), trained diabetic with Alpha-Lipoic Acid and insulin (RTDAI), trained diabetic with L-carnitine and insulin (RTDLCI), and trained diabetic with Alpha-Lipoic Acid, L-carnitine, and insulin (RTDALCI). After diabetes induction with a streptozotocin solution, the rats were diagnosed with diabetic neuropathy following hyperalgesia tests conducted over the next 6 weeks. Subsequently, they were adapted to and subjected to a swimming protocol of 5 days/week for 4 weeks. Treatment with Alpha-Lipoic Acid (100g/kg) and L-carnitine (100g/kg) was administered via gavage, while insulin (4 U/day) was administered subcutaneously, 7 days/week. The analyses performed included systolic blood pressure (SBP), anthropometric evaluation, organosomatic index, histopathology, morphometry, immunohistochemistry, cardiac injury markers, and oxidative stress. Diabetic rats presented higher initial SBP values compared to the RS and RTC groups. At the final SBP assessment, diabetic rats treated with insulin, L-carnitine, and alpha-lipoic acid, either in combination or alone, had similar values to those of the RS and RTC groups. In the anthropometric evaluation, the diabetic rats experienced body weight loss. However, by the end of treatment, only the RTD group showed significant differences compared to the other groups, with the weight loss consequently leading to a higher organosomatic index. Regarding cardiac injury markers, total CK, CK-MB, the relative CK-MB index, and LDH in the groups treated with insulin, L-carnitine, and alpha-lipoic acid, either combined or not, were not statistically different from the RS and RTC groups. Only the RTD group showed a positive result for cTnI.