Name: SILAS NASCIMENTO RONCHI
Publication date: 09/03/2022
Advisor:
Name |
Role |
|---|---|
| NAZARE SOUZA BISSOLI | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| ANA RAQUEL SANTOS DE MEDEIROS GARCIA | External Examiner * |
| GIRLANDIA ALEXANDRE BRASIL AMORIM | External Examiner * |
| GLAUCIA RODRIGUES DE ABREU | Internal Examiner * |
| NAZARE SOUZA BISSOLI | Advisor * |
| SILVANA DOS SANTOS MEYRELLES | Internal Examiner * |
Summary: Oxandrolone (OXA), a synthetic analogue of testosterone, is used in clinical practice because most of its effects are anabolic and low androgenic, so its abuse for aesthetic purposes has spread. In view of this problem and the scarce literature on the effects of this drug on renal parameters, this study aims to analyze the influence of OXA treatment on cardiac contractile function, autonomic tone and renal function in young rats. For this, 4-week-old animals were separated into 3 experimental groups (n=6 each). Control Group (CON): received 0.1 mL of Carboxymethylcellulose (CMC, 0.5%), L-OXA Group (Oxandrolone 2.5 mg/kg/day) and H-OXA Group (Oxandrolone 37.5 mg/kg /day). The administration was made orally (gavage), daily for 4 weeks. After the treatment period, the animals were anesthetized and, for the evaluation of contractile function, the right carotid artery was catheterized, and this catheter was inserted up to the left ventricle for the measurement of contractility parameters. For the evaluation of the autonomic tone, there was the catheterization of femoral arteries and veins of other groups of treated animals and the same was estimated through selective pharmacological blockers. For these assays, only the CON and H-OXA groups were used. For the evaluation of renal function, the animals in the CON, L-OXA and H-OXA groups, WHERE after treatment, the trachea, femoral artery and vein and bladder were catheterized to facilitate breathing, blood collection, inulin and paraaminohippurate infusion and collection of urine, respectively. Through serial blood and urine collections, glomerular filtration rates (GFR), renal plasma flow (RPF), renal blood flow (RBF) and renal vascular resistance (RVR) were calculated. Cardiac tissue was reserved for study of expression of calcium mobility proteins and histological studies and kidney tissue was referred for histological analysis and AOPP and TBAR`s. There was no difference in the autonomic tone analyses, however, the LVPS was increased in the H-OXA group. The treatment was not able to promote changes in +dP/dt max and -dP/dt min. The same was found when analyzing the Tau. Western blot analysis revealed that the expression of the SERCA2a protein increased in the H-OXA group, with no difference in the other contractility proteins analyzed. There was an increase in the p-PLB/PLB and SERCA2a/PLB ratios indicating activity of the proteins involved. There was also a significant increase in ACE protein expression. For renal function, treatment with OXA reduced inulin clearance represents the negative influence of treatment on GFR. Without changing the other parameters analyzed. Histology revealed cardiac hypertrophy and extensive collagen deposition in both cardiac and renal tissue. It is estimated that the alterations found have a direct role in the tissue renin-angiotensin system that induces the generation of oxidative stress, causing sub-clinical alterations from the cardiac point of view and extensive damage to renal function at all doses studied.
