Shin Jin-Young, Han Ji-Hee, Ko Je-Won, Park Sung-Hyeuk, Shin Na-Rae, Jung Tae-Yang, Kim Hyun-A, Kim Sung-Hwan, Shin In-Sik, Kim Jong-Choon
Ministry of Food and Drug Safety, Cheongju, Korea.; College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
Lab Anim Res. 2016 Dec;32(4):200-207. doi: 10.5625/lar.2016.32.4.200. Epub 2016 Dec 23.
This study investigated the protective effects of diallyl disulfide (DADS) against acetaminophen (AAP)-induced acute renal injury in male rats. We also investigated the effects of DADS on kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), which are novel biomarkers of nephrotoxicity in renal tissues, in response to AAP treatment. The following four experimental groups were evaluated: (1) vehicle control, (2) AAP (1,000 mg/kg), (3) AAP&DADS, and (4) DADS (50 mg/kg/day). AAP treatment caused acute kidney injury evidenced by increased serum blood urea nitrogen (BUN) levels and histopathological alterations. Additionally, Western blot and immunohistochemistry analysis showed increased expression of KIM-1 and NGAL proteins in renal tissues of AAP-treated rats. In contrast, DADS pretreatment significantly attenuated the AAP-induced nephrotoxic effects, including serum BUN level and expression of KIM-1 and NGAL proteins. Histopathological studies confirmed the renoprotective effect of DADS. The results suggest that DADS prevents AAP-induced acute nephrotoxicity, and that KIM-1 and NGAL may be useful biomarkers for the detection and monitoring of acute kidney injury associated with AAP exposure.
本研究调查了二烯丙基二硫醚(DADS)对乙酰氨基酚(AAP)诱导的雄性大鼠急性肾损伤的保护作用。我们还研究了DADS对肾损伤分子-1(KIM-1)和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的影响,这两种蛋白是肾组织中肾毒性的新型生物标志物,与AAP治疗有关。对以下四个实验组进行了评估:(1)溶剂对照组,(2)AAP(1000 mg/kg)组,(3)AAP&DADS组,以及(4)DADS(50 mg/kg/天)组。AAP治疗导致急性肾损伤,表现为血清血尿素氮(BUN)水平升高和组织病理学改变。此外,蛋白质印迹法和免疫组织化学分析显示,AAP处理的大鼠肾组织中KIM-1和NGAL蛋白表达增加。相比之下,DADS预处理显著减轻了AAP诱导的肾毒性作用,包括血清BUN水平以及KIM-1和NGAL蛋白的表达。组织病理学研究证实了DADS的肾脏保护作用。结果表明,DADS可预防AAP诱导的急性肾毒性,并且KIM-1和NGAL可能是检测和监测与AAP暴露相关的急性肾损伤的有用生物标志物。