Efeitos do Ramipril, Captopril e Sinvastatina na Injúria da Preservação a Frio de Rins de Ratos

Introducao: A preservacao a frio geralmente e utilizada para minimizar a injuria renal durante a preservacao. Testamos se a adicao de sinvastatina, captopril, e ramipril a solucao de Euro-Collins (EC) ou o pre-tratamento de rins de ratos doadores com ramipril e/ou sinvastatina poderia reduzir a injuria da preservacao renal. Metodos: Inicialmente, adicionamos ramipril e sinvastatina a solucao de EC, contendo fragmentos de rins de ratos que foram preservados a frio por 24 horas (n=6). O dano tecidual foi avaliado pela liberacao de desidrogenase latica (DHL). In vivo, ramipril, por gavagem, e/ou sinvastatina, intraperitonealmente, foram administrados aos ratos doadores 18h antes da nefrectomia.Fragmentos renais foram estocados a frio em EC durante 24h ou 48h. O dano tecidual foi avaliado, utilizando a liberacao de DHL, substâncias reativas ao acido tiobarbiturico (TBARS), teste do MTT e pelo exame morfologico apos 0, 24, e 48h (n=10). Concomitantemente, captopril foi acrescentado a solucao de EC e fragmentos adicionais dos rins de ratos controles foram estocados a frio durante 24h e 48h, com dano tecidual avaliado por liberacao de DHL e exame histologico. Resultados: A adicao de ramipril e sinvastatina a solucao de EC nao afetou a viabilidade dos fragmentos renais (p>0,05). A aducao de captopril na solucao de EC tambem nao melhorou a viabilidade durante a preservacao a frio, avaliada pela liberacao de desidrogenase latica e pelo escore histologico (p>0,05). O pre-tratamento dos doadores renais com ramipril e/ou sinvastatina nao alterou significativamente o MTT, MDA, DHL ou escores histologicos. Discussao: Inibidores da ECA e estatinas protegem contra a injuria da isquemia-reperfusao (I/R) apos pre-tratamento por alguns dias e reduzem o estresse oxidativo e marcadores inflamatorios e poderiam melhorar a capacidade antioxidante da solucao de EC... Background: Cold storage is generally used to minimize kidney injury during preservation. We tested whether or not addition of simvastatin, captopril, and ramipril in the Euro-Collins solution (EC) or pre-treatment of rat kidney donors with ramipril and/or simvastatin reduced preserved kidney injury.Methods: We first added ramipril and simvastatin to EC with rat kidney fragments that were cold-stored for 24 hours (n=6). Tissue damage was assessed by lactate dehydrogenase (LDH). In vivo, ramipril, by gavage, and/or intraperitoneal simvastatin , were administered to donor rats 18h before nephrectomy. Kidney fragments were cold-stored in EC for 24h or 48h. Tissue damage was assessed by LDH release, TBARS, MTT-assay, and by morphologic assessment at 0, 24, and 48h (n=10). Concomitantly, captopril was added to EC and additional fragments of control rat kidneys were coldstored for 24 and 48h, with damage assessed by LDH release and histology. Results: The addition of ramipril and simvastatin to EC solution did not change the viability of rat kidney fragments (p>0.05). The addition of captopril in the EC solution also did not improve cold-storage viability, as assessed by LDH release levels and histological scores (p>0.05). Pre-treatment of kidney donors with ramipril and/or simvastatin did not significantly change MTT, MDA, LDH levels or histological scores.Discussion: ACEIs and statins protect against organ I/R injury after donor pre-treatment for a few days and reduce oxidant stress and inflammatory markers, and could improve the antioxidant capacity of EC solution. In the tested concentrations, inclusion of captopril, ramipril, and simvastatin in the EC solution did not improve the preservation quality of cold-stored rat kidney fragments...