Single or Divided Administration of Cisplatin Can Induce Inflammation and Oxidative Stress in Male Sprague-Dawley Rats

B. R. A. Sidharta, B. Purwanto, B. Wasita, V. Widyaningsih, S. Soetrisno
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引用次数: 2

Abstract

BACKGROUND: Cisplatin is one of the most potent chemotherapy drugs to treat various types of cancer, however the use of cisplatin has some the adverse effect, such as the increase of oxidative stress and inflammation by malondialdehyde (MDA) and nuclear factor kappa B (NF-kB) activation. Since the dosing of cisplatin is critical, we observed the effect of single and multiple doses of cisplatin injection on rats’ inflammation and oxidative stress level.METHODS: Total of 27 male Sprague-Dawley rats were divided into 9 sub-groups, each consisted of 3 rats. The baseline sub-group received no treatments; Group 1 (sub-group 1.1, 1.2, 1.3, and 1.4) were administered one single dose of 5 mg/kg BW/intravenously (i.v) of cisplatin; and Group 2 (sub-group 2.1, 2.2, 2.3, and 2.4) were given 0.2 mg/kg BW/i.v of cisplatin twice a week for two months. Rats were observed for their body weight, NF-kB, and MDA level based on the assigned group. RESULTS: Body weight loss was observed in the 1st week after treatment for Group 1, and 7th week for Group 2. Group 1 and Group 2 showed increasing level of NF-kB and MDA since the 1st observation, which was the 1st week and 5th week, respectively. NF-kB and MDA and levels were also significantly increasing in both groups for every week of observation (p<0.05).CONCLUSION: Cisplatin injection either in single or divided dose can induce inflammation and oxidative stress thus decrease the body weight. However, dividing cisplatin in smaller dose can delay the inflammation effect on subjects.KEYWORDS: cisplatin dose, MDA, NF-kB, body weight, inflammation, oxidative stress 
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顺铂单次或分次给药可诱导雄性Sprague-Dawley大鼠炎症和氧化应激
背景:顺铂是治疗各种类型癌症的最有效的化疗药物之一,然而使用顺铂也有一些不良反应,如丙二醛(MDA)和核因子κ B (NF-kB)活化引起氧化应激和炎症的增加。由于顺铂的剂量至关重要,我们观察了单剂量和多剂量顺铂注射对大鼠炎症和氧化应激水平的影响。方法:27只雄性Sprague-Dawley大鼠随机分为9个亚组,每组3只。基线亚组未接受任何治疗;1组(1.1、1.2、1.3和1.4亚组)给予顺铂单剂量5 mg/kg体重/静脉注射(iv);组2(2.1、2.2、2.3和2.4亚组)给予0.2 mg/kg BW/i。V的顺铂,每周两次,持续两个月。观察各组大鼠体重、NF-kB、MDA水平。结果:组1治疗后第1周体重减轻,组2治疗后第7周体重减轻。实验组1和实验组2的NF-kB和MDA水平较第1次观察(第1周和第5周)有所升高。两组血清NF-kB、MDA及水平均显著升高(p<0.05)。结论:单次或分次注射顺铂均可引起炎症和氧化应激,从而降低体重。然而,较小剂量的顺铂可延缓受试者的炎症反应。关键词:顺铂剂量、MDA、NF-kB、体重、炎症、氧化应激
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