Avaliação do efeito antirreabsortivo de um derivado semissintético do triterpeno 3β, 6β, 16β-trihidroxilup-20(29)-eno de combretum leprosum no modelo de osteoporose induzida por glicocorticóide em ratos wistar

Abstract

Osteoporosis is an osteometabolic disease characterized by low bone density and peripheral bone tissue microarchitecture, with consequent bone porosity and increased risk of fractures. Chronic use of glucocorticoids is the most common cause of secondary osteoporosis. Glucocorticoids decrease the maturation, lifespan and function of osteoblasts and osteocytes, consequently leading to bone loss, in addition, they alter the balance/resorption formation, causing an increase in formation and changes in bone resistance and can cause changes in microarchitecture of the bone, microlesions caused in the tissue. Cobretum leprosum Mart. is a species popularly used as a healing and anti-inflammatory agent. From a secondary metabolite CL-1 from the flowers of Cobretum leprosum Mart. a semi-synthetic derivative CL-P2 was produced, which demonstrated antinociceptive and ant i -inflammatory effects, and no toxicity when administered for 14 days in mice. This study sought to evaluate the antiresorptive effect of CL-P2 in the model of osteoporosis caused by glucocorticoids in rats. The experimental protocol was approved by the Ethics Committee on the Use of Animals (ECUA) of the Federal University of Ceará, under number 6655221121. Osteoporosis was induced through injection (I.M.) of dexamethasone (7 mg/kg) once every 7 days, for 65 days. On the 36th day, treatment (per os) with CL-P2 (0.01 or 0.1 mg/kg) was started for 30 consecutive days. After this time interval, the animals were euthanized and the femurs and lumbar vertebrae were collected for analysis through: microcomputed tomography (micro-CT), biomechanical tests (three-point flexural strength), histomorphometric analyzes (H&E and Picrosirius Red) and micro -Raman spectrometry, in addition the heart and liver were collected for toxicity analysis (H&E). CL-P2 significantly improved (p<0.05) the bone microarchitecture of the lu mbar vertebrae, marked by an increase in the volume and number of trabeculae (18.78%) and (17.49%) respectively, and an increase in mineral density bone in (23.24%). CL-P2 increased the number (p<0.05) of osteocytes by (30.02%) and was able to reverse the decrease in osteoblasts and the increase in osteoclasts caused by dexamethasone in the femurs and lumbar vertebrae compared to the non-group. treated. The biomechanical properties of the femurs showed better results in the groups treated with CL-P2, which also showed an increase (p<0.05) in total, type I and type III collagen in lumbar vertebrae. Furthermore, it did not present histopathological signs of cardiac toxicity and demonstrated hepatoprotective activity. These results suggest that CL-P2 is a safe tool and can protect bone from the deleterious effects caused by glucocorticoids on bone tissue