ABSTRACT Acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) generally leads to glomerular damage associated with the tubular injury characteristic of this disease. D-005, a lipid extract obtained from the fruit of Acrocomia crispa, prevents renal I/R-induced tubular injury. The aim of this work was to evaluate the effect of D-005 on histomorphometric changes in glomeruli of rat kidneys subjected to renal I/R. Forty-two male Sprague-Dawley rats were distributed into seven groups: a non-damaged group (negative control) and six groups subjected to renal I/R, previously treated with: vehicle (positive control), D-005 (25, 100, 200 and 400 mg/kg) and Dexamethasone (3 mg/kg). Renal I/R consisted on 30 min of bilateral ischemia and 24 h of reperfusion. Kidneys were processed according to the general histological technique. Glomerular morphology and morphometry were studied using Image J software. Negative control group was characterized by the presence of a glomerular structure within normal parameters, while positive control group showed thickening of the Bowman's capsule parietal layer, vascular dilation with segmentation of the capillary tuft, synechiae and narrowing of Bowman's space; as well as decrease of glomerular area. D-005 (25-400 mg/kg) diminished glomerular injuries caused by renal I/R and induced restoration of glomerular area. In conclusion, single oral treatments with D-005 prevented glomerular histopathological changes induced by renal I/R, which could be associated with previous findings of tubular protection, as well as the antioxidant and anti-inflammatory properties of this substance.

RESUMEN La lesión renal aguda (LRA) inducida por isquemia-reperfusión (I/R) renal generalmente conlleva a un daño a nivel glomerular asociado a la lesión tubular característica de esta enfermedad. El D-005, extracto lipídico obtenido del fruto de Acrocomia crispa, previene la lesión tubular inducida por I/R renal. El objetivo de este trabajo fue evaluar el efecto del D-005 sobre los cambios histomorfométricos en glomérulos de riñones de ratas sometidas a I/R renal. Se emplearon 42 ratas machos Sprague-Dawley distribuidas en siete grupos: un grupo sin daño (control negativo) y seis grupos sometidos a I/R renal, tratados previamente con: vehículo (control positivo), D-005 (25, 100, 200 y 400 mg/kg) y Dexametasona (3 mg/kg). La I/R renal consistió en 30 min de isquemia bilateral y 24 h de reperfusión. Los riñones se procesaron según la técnica histológica general. Se estudió la morfología y morfometría glomerular usando el programa Image J. El grupo control negativo se caracterizó por presentar una estructura glomerular dentro de los parámetros normales, mientras que el control positivo presentó engrosamiento de la capa parietal de la cápsula de Bowman, dilatación vascular con segmentación del penacho capilar, sinequias y estrechamiento del espacio de Bowman; así como disminución del área glomerular. El D-005 (25-400 mg/kg) disminuyó los daños glomerulares causados por la I/R renal e indujo la restauración del área glomerular. En conclusión, los tratamientos orales únicos con D-005 previnieron los cambios histopatológicos glomerulares inducidos por I/R renal, lo que puede estar asociado a los hallazgos previos de protección tubular, así como a las propiedades antioxidantes y antiinflamatorias de esta sustancia.

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.

The medical histories and the anatomopathological diagnoses of 382 renal biopsies performed in this center from 1995 to 1998 were reviewed. 241 with diagnosis of primary glomerulopathies studied by optic microscopy, immunohistochemistry and some of them by electronic microscopy were selected for research. A higher incidence was observed among patients aged 21-30 (29.87 %). White individuals were the most affected (53.11 %). The segmentary focal glomerulosclerosis proved to be the most frequent variety of glomerulopathy (22.82 %), followed by proliferative mesangial glomerulosclerosis (17.82 %) and proliferative endocapillary glomerulonephritis (16.18 %). Sclerosing glomerulonephritis was the least common (1.65 %). Clinical and laboratory aspects were analyzed and it was found that proteinuria and arterial hypertension were present in segmentary focal glomerulosclerosis and nephrotic syndrome with 87.27 and 41.81 %, respectively, and in 38.18 % in this variety. The most relevant aspect in the proliferative mesangial glomerulonephritis was proetinuria with 93.02 %, whereas proteinuria, hematuria and arterial hypertension were the most significant in the proliferative endocapillary glomerulonephritis. Proteinuria was the most frequent manifestation in all the varieties of glomerulopathies. Immunofluorescence studies were conducted to assess the positivity of immunoglobulins and complements contributing to corroborate the diagnosis.

Se revisaron las historias clínicas y los diagnósticos anatomopatológicos de 382 biopsias renales realizadas en este centro desde 1995 a 1998. Se seleccionaron para esta investigación 241 con diagnóstico de glomerulopatías primarias estudiadas por microscopia óptica, inmunohistoquímica, y algunas por microscopia electrónica. Se observó mayor incidencia entre los 21 y 30 años (29,87 %) y la raza blanca fue la más afectada (53,11 %). Se comprobó que la variedad de glomerulopatía más frecuente resultó la glomerulosclerosis segmentaria focal (22,82 %) seguida por la glomerulosclerosis proliferativa mesangial (17,82 %) y la glomerulonefritis proliferativa endocapilar (16,18 %), la menos frecuente fue la glomerulonefritis esclerosante ( 1,65 %). Se analizaron aspectos clínicos y de laboratorio y se constató que la proteinuria y la hipertensión arterial se presentaron en el 87,27 y 41,81 %, respectivamente, en la glomerulosclerosis segmentaria focal y el síndrome nefrótico, en el 38,18 %. En la glomerulonefritis proliferativa mesangial, el aspecto más relevante lo constituyó la proteinuria con 93,02% y en la glomerulonefritis proliferativa endocapilar, la proteinuria, la hematuria y la hipertensión arterial. La proteinuria fue la manifestación más frecuente en todas las variedades de glomerulopatías. Se realizaron estudios de inmunofluorescencia para valorar la positividad de inmunoglobulinas y complementos que ayudan a corroborar el diagnóstico.