多柔比星（DOX）是一种类蒽环抗生素，被用于治疗各种癌症。肾毒性是DOX的严重副作用之一，因此，DOX诱导的肾毒性模型广泛应用于研究肾病。本研究的目的是探讨水杨酸衍生物N-(2-羟基苯基)乙酰胺（NA-2）在DOX诱导的肾毒性大鼠模型中可能的抗炎和肾保护效应。NA-2的体外抗炎潜力通过全血氧化爆发和一氧化氮（NO）实验体现，对正常人成纤维细胞（BJ）、人胚胎肾细胞（HEK-293）和正常猴子肾上皮细胞（Vero）无毒性。体内研究包括五组：正常对照组、DOX（6 mg/kg DOX-i.v.经尾静脉）组、NA-2处理对照组-i.p.、NA-2/DOX处理组-i.p.和泼尼松龙/DOX处理组。给予DOX治疗7天后，尿蛋白水平>50 mg/kg/day的大鼠被选中。治疗组大鼠每天腹腔注射NA-2（10 mg/kg/day）3周，每周监测尿蛋白排泄和体重。采用定量聚合酶链式反应（qPCR）分析白细胞介素（IL）-1β、IL-6、肿瘤坏死因子（TNF）-α、单核细胞趋化蛋白（MCP）-1和肾损伤分子（KIM）-1的mRNA表达。蛋白质表达通过免疫组化分析。NA-2减轻了DOX引起的血清和尿液水平变化，并改善了肾组织的炎症状况。组织病理学发现显示NA-2具有保护作用，病变较轻。我们得出结论，NA-2可以在功能、生化和病理方面保护免受DOX诱导的肾损伤，与此同时改善肾脏的炎症状况。版权所有 © 2023 Elsevier B.V. 保留所有权利。

Doxorubicin (DOX) is an anthracyclin antibiotic used for the treatment of various cancers. Nephrotoxicity is among the serious side effects of DOX, therefore, DOX-induced nephrotoxic model has been widely used to study nephropathies. The objectives of this study is to investigate the possible anti-inflammatory and nephroprotective effects of salicylic acid derivative, N-(2-hydroxy phenyl) acetamide (NA-2), in a rat model of DOX-induced nephrotoxicity. The in vitro anti-inflammatory potential of NA-2 was manifested by whole blood oxidative burst and nitric oxide (NO) assays with no toxicity on normal human fibroblast (BJ) cells, human embryonic kidney (HEK-293) cells, and normal monkey kidney epithelial (Vero) cells. The in vivo study included five groups: Normal control, DOX (6 mg/kg DOX-i.v.via tail vein), NA-2 treated control-i.p., NA-2/DOX treated-i.p., and prednisolone/DOX treated. After 7 days of DOX administration, rats with urinary protein level of >50 mg/kg/day were selected. Treatment group rats received i.p. doses of NA-2 (10 mg/kg/day) for 3 weeks with weekly monitoring of urinary protein excretion and body weights. mRNA expression of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and kidney injury molecule (KIM)-1 was analyzed by quantitative polymerase chain reaction (qPCR). Protein expressions were analyzed by immunohistochemistry. NA-2 attenuated DOX-induced changes in serum and urine levels, and improved inflammatory profile of the renal tissue. Histopathological findings revealed protective effects of NA-2 showing lesser lesions. We conclude that NA-2 is able to protect against DOX-induced renal damage functionally, biochemically and histopathologically with corresponding improvement in the kidney inflammatory profile.Copyright © 2023 Elsevier B.V. All rights reserved.