Raoof Saeed, Rezaei Shiva, Zargari Mehryar, Mirzaei Mansoureh, Hosseinimehr Seyed Jalal, Karimpour Malekshah Abbasali, Talebpour Amiri Fereshteh
Department of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Iran J Basic Med Sci. 2025;28(5):655-661. doi: 10.22038/ijbms.2025.83903.18155.
Cyclophosphamide (CP) is a chemotherapeutic drug used to treat various tumors. It causes nephrotoxicity by producing reactive oxygen species. Sinapic acid (SA) exhibits anti-oxidant, antiapoptotic, and anti-inflammatory activities at low doses as a phenylpropanoid. This study aimed to investigate the protective effects of SA on SP-induced renal injury.
Forty-eight BALB/c mice were randomly divided into control, SA (for seven consecutive days, with two doses of 5 and 10 mg/kg), CP (single dose, 200 mg/kg), and CP + SA (5 and 10 mg/kg). On the 10th day of the study, mice were examined by renal function markers (Urea and Creatinine), oxidative stress markers (MDA and GSH), histopathological, and immunohistochemical assays (caspase-3 and NF-kB kidney).
MDA levels increased and GSH levels decreased significantly in CP-treated mice. In addition, the histopathological structure of the kidney tissue in CP-treated mice showed significantly severe kidney tissue damage associated with increased urea and creatinine. The administration of SA in CP-treated mice significantly reduced serum urea and creatinine concentrations. In addition, the immunohistochemical staining of caspase- 3 and NF-kB decreased significantly in the CP + SA group compared to CP-treated mice.
Overall, our study suggests that sinapic acid, a substance with antioxidant, antiapoptotic, and anti-inflammatory properties, can be used as a complementary therapy to protect nephrotoxicity against CP.
环磷酰胺(CP)是一种用于治疗多种肿瘤的化疗药物。它通过产生活性氧导致肾毒性。芥子酸(SA)作为一种苯丙烷类化合物,在低剂量时具有抗氧化、抗凋亡和抗炎活性。本研究旨在探讨SA对CP诱导的肾损伤的保护作用。
将48只BALB/c小鼠随机分为对照组、SA组(连续7天,剂量分别为5和10mg/kg)、CP组(单次剂量,200mg/kg)和CP+SA组(5和10mg/kg)。在研究的第10天,通过肾功能指标(尿素和肌酐)、氧化应激指标(丙二醛和谷胱甘肽)、组织病理学和免疫组织化学分析(肾组织中的半胱天冬酶-3和核因子-κB)对小鼠进行检测。
CP处理的小鼠丙二醛水平显著升高,谷胱甘肽水平显著降低。此外,CP处理的小鼠肾组织的组织病理学结构显示与尿素和肌酐升高相关的严重肾组织损伤。在CP处理的小鼠中给予SA可显著降低血清尿素和肌酐浓度。此外,与CP处理的小鼠相比,CP+SA组中半胱天冬酶-3和核因子-κB的免疫组织化学染色显著降低。
总体而言,我们的研究表明,具有抗氧化、抗凋亡和抗炎特性的芥子酸可作为一种辅助疗法来保护肾脏免受CP的肾毒性。