Resumo Introdução: Lesão renal aguda induzida por aminoglicosídeos é uma patologia intimamente ligada a reações oxidativas e inflamatórias. Considerando efeitos antioxidantes e anti-inflamatórios relatados anteriormente do D-005, um extrato lipídico de frutos da palmeira cubana Acrocomia crispa (Arecaceae), este trabalho avaliou efeitos do D-005 na LRA induzida por canamicina. Métodos: Dividiu-se ratos Wistar machos em 7 grupos: controle negativo (veículo, Tween 65/H2O) e seis grupos tratados com canamicina para induzir LRA: controle positivo (veículo), D-005 (25, 100, 200, 400 mg/kg) e extrato de semente de uva (ESU, 200 mg/kg). D-005, veículo, e tratamentos orais com ESU foram administrados uma vez por dia durante sete dias, 1 h antes da canamicina (500 mg/kg, i.p.). Avaliou-se concentrações séricas de ácido úrico e ureia, histopatologia renal e marcadores oxidativos (malondialdeído (MDA), grupos sulfidrila (SH), atividade de catalase (CAT)). Resultados: D-005 reduziu significativamente níveis de ácido úrico e ureia, partindo de D-005 100 mg/kg. Histopatologicamente, D-005, em todas as doses testadas, protegeu estruturas do parênquima renal (glomérulos, túbulos proximais e interstício). Estes achados foram acompanhados por uma redução significativa das concentrações de MDA e grupo SH, e pela restauração da atividade CAT. As maiores porcentagens de inibição foram obtidas com a dose de 400 mg/kg. ESU, a substância de referência, também evitou alterações bioquímicas e histopatológicas induzidas por canamicina, reduziu MDA e grupos SH e restaurou atividade CAT. Conclusão: A administração de doses orais repetidas de D-005 protegeu significativamente contra LRA induzida por canamicina, que pode estar associada aos efeitos antioxidantes e anti-inflamatórios deste extrato.

Abstract Introduction: Aminoglycoside-induced acute kidney injury (AKI) is a pathology closely linked to oxidative and inflammatory reactions. Taking into account the previous reported antioxidant and anti-inflammatory effects of D-005, a lipid extract obtained from Cuban palm Acrocomia crispa (Arecaceae) fruits, this work aimed to evaluate the effects of D-005 on kanamycin-induced AKI. Methods: Male Wistar rats were divided into 7 groups: negative control (vehicle, Tween 65/H2O) and six groups treated with kanamycin to induce AKI: positive control (vehicle), D-005 (25, 100, 200, and 400 mg/kg) and grape seed extract (GSE, 200 mg/kg). D-005, vehicle, and GSE oral treatments were administered once daily for seven days, 1 h before kanamycin (500 mg/kg, i.p.). Serum uric acid and urea concentrations, renal histopathology, and oxidative markers (malondialdehyde (MDA), sulfhydryl (SH) groups, and catalase (CAT) activity) were assessed. Results: D-005 significantly reduced uric acid and urea levels, starting from D-005 100 mg/kg. Histopathologically, D-005, at all the tested doses, protected renal parenchyma structures (glomeruli, proximal tubules, and interstitium). These findings were accompanied by a significant reduction of MDA and SH group concentrations as well as restoration of CAT activity. The highest percentages of inhibition were obtained with the dose of 400 mg/kg. GSE, the reference substance, also prevented kanamycin-induced biochemical and histopathological changes, as well as reduced MDA and SH groups and restored CAT activity. Conclusion: The administration of repeated oral doses of D-005 significantly protected against kanamycin-induced AKI, which could be associated with the antioxidant and anti-inflammatory effects of this extract.

ABSTRACT Acute Kidney Injury is a disease that is characterized by a deterioration of renal function and represents a global health problem due to morbidity and mortality associated with its prevalence. Currently, there is no effective treatment that prevents its development or avoids its sequelae. The objective of the present work is to update the knowledge and terminology of Acute Kidney Injury in terms of: designation, types, pathophysiology, histopathological changes, most used animal models and treatments. The term Acute Kidney Injury is used to define this disease and the three types of Acute Kidney Injury (functional or prerenal, intrinsic or renal and obstructive or postrenal) are characterized. The pathophysiology of Acute Kidney Injury, in which oxidative stress and inflammatory response play a key role, is explained. The histopathological changes that occur in the renal parenchyma during the intrinsic or renal Acute Kidney Injury are described, the most characteristic being acute tubular injury. On the other hand, the contribution of the animal models of ischemia/reperfusion and nephrotoxicity to the identification of nephroprotective candidates from synthetic and natural antioxidant substances is explained. It is concluded that, in this current context, it is necessary to address the new approaches to the development and progression of Acute Kidney Injury and the new safer and more effective therapeutic alternatives.

RESUMEN La Lesión Renal Aguda es una enfermedad que se caracteriza por un deterioro de la función renal y que representa un problema de salud a nivel mundial por la morbi-mortalidad asociada a su prevalencia. Actualmente, no se cuenta con un tratamiento efectivo que prevenga su desarrollo o evite sus secuelas. El objetivo del presente trabajo es actualizar los conocimientos y la terminología de la Lesión Renal Aguda en cuanto a: denominación, tipos, fisiopatología, cambios histopatológicos, modelos animales más empleados y tratamientos. Se utiliza el término Lesión Renal Aguda para definir esta enfermedad y se caracterizan los tres tipos de Lesión Renal Aguda (funcional o prerrenal, intrínseca o renal y obstructiva o postrenal). Se explica la fisiopatología de la Lesión Renal Aguda, en la que el estrés oxidativo y la respuesta inflamatoria desempeñan un papel primordial. Se describen los cambios histopatológicos que tienen lugar en el parénquima renal durante la Lesión Renal Aguda intrínseca o renal, siendo el más característico la lesión tubular aguda. Por otra parte, se explica la contribución de los modelos animales de isquemia/reperfusión y de nefrotoxicidad a la identificación de candidatos nefroprotectores a partir de sustancias antioxidantes sintéticas o naturales. Se concluye que, en este contexto actual, es necesario abordar los nuevos enfoques sobre el desarrollo y progresión de la Lesión Renal Aguda y las nuevas alternativas terapéuticas más seguras y eficaces.