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.引言与摘要：氨基糖苷类诱导的急性肾损伤（Aminoglycoside-induced acute kidney injury, AKI）是一种与氧化应激及炎症反应密切相关的病理状态。鉴于此前已有研究报道了从古巴棕榈*Acrocomia crispa*（棕榈科，Arecaceae）果实中提取的脂质提取物D-005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，即吐温65/水溶液）以及6个采用卡那霉素造模AKI的组别：阳性对照组（给予赋形剂）、D-005组（25、100、200及400 mg/kg）与葡萄籽提取物（grape seed extract, GSE）组（200 mg/kg）。每日一次口服给予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）给药前1小时完成给药。检测指标包括血清尿酸与尿素浓度、肾脏组织病理学变化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：D-005在剂量达到100 mg/kg时即可显著降低血清尿酸与尿素水平。组织病理学分析显示，所有受试剂量的D-005均可保护肾实质结构（肾小球、近端肾小管与肾间质）。上述保护作用同时伴随MDA与SH基团浓度的显著降低，以及CAT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GSE同样可预防卡那霉素诱导的生化与组织病理学改变，降低MDA与SH基团含量并恢复CAT活性。 结论：反复口服给予D-005可显著对抗卡那霉素诱导的AKI，其作用机制可能与该提取物的抗氧化与抗炎活性相关。