Karwasra Ritu, Kalra Prerna, Gupta Yogendra Kumar, Saini Deepika, Kumar Ajay, Singh Surender
Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India.
Department of Pharmaceutical Chemistry, Kurukshetra University, Kurukshetra 136119, India.
Food Funct. 2016 Jul 13;7(7):3091-101. doi: 10.1039/c6fo00188b.
Cisplatin is a chemotherapeutic agent, but the therapeutic utility is limited due to its dose dependent nephrotoxicity. The aim of the present study was to evaluate the nephroprotective effect of pomegranate in cisplatin-induced acute kidney injury. Wistar rats were allocated into six groups as follows: the normal control, cisplatin-induced, pomegranate rind extract treatment (50, 100 and 200 mg kg(-1)) and pomegranate rind extract per se group. All the experimental test drugs/vehicle were administered orally for a period of ten days. Intraperitoneal injection of cisplatin (8 mg kg(-1)) was administered on day 7 to all the groups except the normal control and pomegranate per se group. On day 10, cisplatin resulted in significant nephrotoxicity in Wistar rats with a drastic elevation of serum creatinine and BUN, a decline in the concentrations of GSH, MDA and superoxide dismutase (SOD), and an elevation in the TNF-α level in renal tissues. Pathological changes in renal tissues were examined by histopathology and dysfunction in mitochondria and proximal tubule cells was detected by transmission electron microscopy. The rate of apoptosis and the expression of caspase-3, Il-1β and IL-6 in rat renal tissues were detected by immunohistochemistry. The administration of pomegranate at a dose of 200 mg per kg body weight significantly (p < 0.001) ameliorates increased serum creatinine and BUN. In parallel to this, pomegranate also exhibits anti-apoptotic activity through the reduction of active caspase-3 expression in kidneys. Additionally, in-silico studies also confirmed a renoprotective effect of pomegranate. The above findings suggest that pomegranate can be used as a dietary supplement in the treatment of cisplatin-induced kidney injury by reducing apoptosis, oxidative stress and inflammation.
顺铂是一种化疗药物,但由于其剂量依赖性肾毒性,其治疗效用受到限制。本研究的目的是评估石榴对顺铂诱导的急性肾损伤的肾保护作用。将Wistar大鼠分为六组,如下:正常对照组、顺铂诱导组、石榴皮提取物治疗组(50、100和200mg/kg(-1))以及石榴皮提取物本身组。所有实验受试药物/赋形剂均口服给药十天。除正常对照组和石榴本身组外,在第7天对所有组腹腔注射顺铂(8mg/kg(-1))。在第10天,顺铂导致Wistar大鼠出现显著的肾毒性,血清肌酐和尿素氮急剧升高,谷胱甘肽、丙二醛和超氧化物歧化酶(SOD)浓度下降,肾组织中肿瘤坏死因子-α水平升高。通过组织病理学检查肾组织的病理变化,并通过透射电子显微镜检测线粒体和近端小管细胞的功能障碍。通过免疫组织化学检测大鼠肾组织中凋亡率以及半胱天冬酶-3、白细胞介素-1β和白细胞介素-6的表达。以每千克体重200mg的剂量给予石榴可显著(p<0.001)改善血清肌酐和尿素氮的升高。与此同时,石榴还通过降低肾脏中活性半胱天冬酶-3的表达表现出抗凋亡活性。此外,计算机模拟研究也证实了石榴的肾脏保护作用。上述研究结果表明,石榴可作为膳食补充剂,通过减少细胞凋亡、氧化应激和炎症来治疗顺铂诱导的肾损伤。