Benefits of D-005, a lipid extract from Acrocomia crispa fruits, in the prevention of acute kidney njury induced by nephrotoxicity in rats

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.

引言：氨基糖苷类诱导的急性肾损伤（acute kidney injury, AKI）是一类与氧化应激及炎症反应紧密相关的病理状态。既往研究表明，D-005——一种从古巴棕榈刺叶棕榈（Acrocomia crispa，棕榈科）果实中提取的脂溶性提取物——具备抗氧化与抗炎活性。本研究旨在评估D-005对卡那霉素诱导的AKI的保护作用。

方法：将雄性Wistar大鼠分为7组：阴性对照组（给予赋形剂吐温65/水溶液），以及6个经卡那霉素造模的AKI模型组：阳性对照组（给予赋形剂）、D-005四个剂量组（25、100、200及400 mg/kg），以及葡萄籽提取物（grape seed extract, GSE，200 mg/kg）对照组。每日单次灌胃给予D-005、赋形剂或GSE，连续给药7天，于卡那霉素（500 mg/kg，腹腔注射）给药前1小时进行给药。本研究检测了各组大鼠的血清尿酸、尿素浓度，肾脏组织病理形态，以及氧化应激标志物：丙二醛（malondialdehyde, MDA）、巯基（sulfhydryl, SH）基团含量与过氧化氢酶（catalase, CAT）活性。

结果：与阳性对照组相比，D-005给药组（剂量≥100 mg/kg）可显著降低血清尿酸与尿素水平。病理组织学分析显示，各受试剂量的D-005均能有效保护肾实质结构（肾小球、近端肾小管及肾间质）免受损伤。同时，D-005可显著降低MDA与巯基基团的异常变化，并恢复CAT活性，其中400 mg/kg剂量组的干预效果最为显著。作为阳性对照的GSE同样可有效阻断卡那霉素诱导的生化与病理组织学改变，降低MDA与巯基基团含量并恢复CAT活性。

结论：反复口服给予D-005可显著减轻卡那霉素诱导的AKI，其保护作用可能与该提取物的抗氧化与抗炎活性密切相关。