Benefits of D-005, a lipid extract from Acrocomia crispa fruits, in the prevention of acute kidney injury 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.

摘要：氨基糖苷类药物诱导的急性肾损伤（AKI）是一种与氧化应激及炎症反应密切相关的病理状态。既往研究已报道D-005——一种从古巴棕榈科刺果椰（Acrocomia crispa）果实中提取的脂质提取物——具有抗氧化与抗炎活性。本研究旨在评估D-005对卡那霉素诱导的急性肾损伤的干预效果。
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急性肾损伤模型组：阳性对照组（给予赋形剂）、D-005组（分别给予25、100、200、400 mg/kg剂量）与葡萄籽提取物（GSE，200 mg/kg）组。每日单次口服给予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（i.p.））给药前1小时给药。检测指标包括血清尿酸与尿素浓度、肾脏组织病理学改变，以及氧化应激标志物：丙二醛（MDA）、巯基（SH）基团含量与过氧化氢酶（CAT）活性。
结果：D-005在100 mg/kg及以上剂量时可显著降低血清尿酸与尿素水平。组织病理学分析显示，各受试剂量的D-005均可对肾实质结构（肾小球、近端肾小管及肾间质）起到保护作用。上述保护作用伴随丙二醛与巯基基团浓度的显著降低，以及过氧化氢酶活性的恢复。其中400 mg/kg剂量的抑制效果最为显著。作为阳性对照的葡萄籽提取物同样可阻断卡那霉素诱导的生化与组织病理学改变，同时降低丙二醛与巯基基团含量并恢复过氧化氢酶活性。
结论：重复口服给予D-005可显著对抗卡那霉素诱导的急性肾损伤，其作用机制可能与该提取物的抗氧化与抗炎活性相关。