#4611 THE INTEREST OF THE COMBINATION OF AN ANTIOXIDANT AND ANGIOTENSIN II RECEPTOR ANTAGONISTS IN THE REDUCTION OF RENAL FIBROSIS

Abstract

Abstract Background and Aims Chronic kidney disease represents one of the frequent pathologies of non-communicable diseases where the mortality rate is high. Oxidative stress is one of the main causes of the deterioration of renal function. The aim of this work is to develop a new therapeutic molecule with an anti-fibrotic effect associated with an antioxidant to increase renal clearance. Method This is an experimental study using the aminonucleoside model of puromycin (PAN) on Sprague-Dawley rats weighing between 100 and 150 g. Mice are resistant to the effect of PAN Administration of PAN can be subcutaneous (SC) intravenous (IV) and intraperitoneal (IP)). The dosage for IV and IP administration of PAN is generally 150 mg/kg body weight and 120 mg/kg body weight for SC administration. Control rats receive an isotonic saline solution. The progression of glomerular lesions to glomerular fibrosis depends on the cumulative dose of PAN. The single injection of PAN induces reversible fibrosis lesions between the seventh and one month and after reinjection irreversible lesions. The mice benefited from PAN 2 injections on the 1st day and on the 40th day. the new molecular association was made on 15 days and 50 days. Results Two to four days after the injection of PAN, a disorganization of the ultrastructure of the pedicels is observed with a flattening of the podocyte feet, an effacement of the pedicels, a modification of the actin cytoskeleton and the disappearance of the diaphragm of cleft. The ultrastructural changes observed 10 days after PAN injection lead to podocyte detachment contemporary with proteinuria. If the aggression continues, podocyte apoptosis is associated with the histological appearance of segmental and focal hyalinosis. After the injection of the molecular combination, a regression of the lesions was observed 15 days after the first injection and 30 days after the second injection. Discussion The anti-fibrotic-antioxidant drug combination has a significant anti-fibrotic effect, especially during the first injection, the effect is less important during the evolution of histological fibrosis. The antioxidant gave a synergistic effect to the anti-fibrotic effect Conclusion The experimental study is very promising concerning the antioxidant ARII molecular association while waiting for the clinical trial that will hopefully be promising for this new association.