Pedram Behnam, Moghadam Ahmad Taghavi, Kamyabi-Moghaddam Zahra, Mavedati Omid, Beigi Babak Abbas, Sharabiyani Adel Khodaei, Dezfuli Ali Bashiri, Khalili Soheil, Bahrami Ali Mohammad, Nasoori Alireza
Department of Pathobiology, Susangerd Branch, Islamic Azad University, Susangerd, Iran.
Tumour Biol. 2015 Jun;36(6):4495-500. doi: 10.1007/s13277-015-3091-1. Epub 2015 Jan 17.
Cisplatin (CP) is a remarkably effective Pt-based anticancer drug, but it also exhibits severe toxic side effects, including nephrotoxicity and ototoxicity, and CP nephrotoxicity is a major constraint for the treatment of solid tumors. This study was designed to evaluate the electrolyte and biochemical changes in dogs with acute kidney injury (acute renal failure) following administration of CP as a chemotherapeutic agent to exhibit broad efficacy in solid tumors. A total of 10 adult male dogs were selected (treated dogs = 7 and control dogs = 3). Cisplatin-treated animals were received 0.75 mg/kg via intravenous for 5 consecutive days. Urine and blood samples on days 0 (pre-dosing), 1, 2, 3, 4, 7, 10, 14, and 28 (post-dosing) were collected. For tracking the signs of toxicity with cisplatin, clinical examination was performed for 2 times a day. Serum samples were assayed urea, creatinine, sodium, chloride, potassium, calcium, phosphorus, and urine samples were used to measure creatinine. Serum creatinine levels indicating renal function (glomerular filtration rate) was 0.66 and 0.94 mg/dL in day 0, respectively, in treatment and control animals. After day 2, a significant change in creatinine was observed in treatment animals. On the end day of the study control and treatments, creatinine was measured with mean of 1.35 and 1.00 mg/dL, respectively. Electrolyte disturbances were observed after several days of cisplatin administration including changes in levels of sodium, potassium, phosphorus, calcium, and chloride. Clinical observations also identified CP toxicity. This study for the first time showed that compensation electrolyte abnormalities in dogs following administration of cisplatin is essential to prevent deaths by daily monitoring and measurement of electrolytes in patients. This may be advantageous if repetitive cycles of chemotherapy or subsequent administration of high dose chemotherapy were planned.
顺铂（CP）是一种非常有效的铂类抗癌药物，但它也会表现出严重的毒副作用，包括肾毒性和耳毒性，而CP肾毒性是实体瘤治疗的主要限制因素。本研究旨在评估将CP作为化疗药物用于实体瘤广泛治疗后，急性肾损伤（急性肾衰竭）犬的电解质和生化变化。共选择了10只成年雄性犬（治疗组犬=7只，对照组犬=3只）。顺铂治疗的动物连续5天静脉注射0.75mg/kg。在给药前第0天、给药后第1、2、3、4、7、10、14和28天采集尿液和血液样本。为追踪顺铂的毒性迹象，每天进行2次临床检查。测定血清样本中的尿素、肌酐、钠、氯、钾、钙、磷，尿液样本用于测量肌酐。治疗组和对照组动物在第0天血清肌酐水平分别为0.66和0.94mg/dL，分别代表肾功能（肾小球滤过率）。给药后第2天，治疗组动物的肌酐出现显著变化。在研究结束日，对照组和治疗组的肌酐测量平均值分别为1.35和1.00mg/dL。顺铂给药几天后观察到电解质紊乱，包括钠、钾、磷、钙和氯水平的变化。临床观察也发现了CP毒性。本研究首次表明，顺铂给药后对犬进行电解质异常补偿对于通过每日监测和测量患者电解质来预防死亡至关重要。如果计划进行重复化疗周期或随后给予高剂量化疗，这可能是有利的。
