姜黄素对顺铂所致大鼠肾毒性的防护作用

目的研究姜黄素(CMN)对顺铂(CDDP)所致肾损害的防护作用,并探讨其可能机制。方法将42只大鼠按体重随机分6组,分别为对照组、CMN组、CDDP组、CMN(204、0和80 mg/kg) CDDP组。CMN连续给予大鼠灌胃3 d,第2天灌胃后1 h腹腔注射CDDP(5.5 mg/kg)。CDDP处理后,分别在第1、3和5天采血,测定血清尿素氮(BUN)和肌酐(CRE)。第5天采血后处死动物,测定肾脏系数、肾皮质匀浆丙二醛(MDA)、谷胱甘肽(GSH)含量和谷胱甘肽过氧化物酶(GSH-Px)活力以及肾组织铂(Pt)含量等。同时利用体外实验观察对抗增殖作用的影响。结果CMN预处理可减轻CDDP引起的肾脏系数升高及BUN、CRE水平升高;能抑制CDDP引起的MDA形成增高;并能提升CDDP引起的GSH含量和GSH-Px活力下降。CMN低剂量的上述作用明显(P<0.05或P<0.01)。CMN防护组与CDDP组的人卵巢癌细胞系和膀胱癌细胞系的半数抑制浓度差异无显著性。结论CMN经口给予能防护CDDP所致的肾损害,其机制可能与其抗氧化作用和清除自由基活性有密切关系。较高剂量CMN未见防护CDDP所致肾毒性的作用,其原因可能与其助氧化作用有关。CMN对CDDP抗肿瘤细胞增殖作用无明显影响。     

两种药物对顺铂所致肾毒性的影响

目的 :研究顺铂所致肾毒性及茶多酚、硫代硫酸钠两种药物对其毒性的影响。方法 :小鼠随机分为对照组、顺铂组、顺铂 +硫代硫酸钠组、顺铂 +茶多酚组。处死小鼠 ,观察血清中的尿素氮 (BUN)和肌酐 (Cr)的变化 ,肾脏病理的变化。结果 :顺铂组小鼠血清尿素氮、肌酐较对照组高且差异有显著性 ;顺铂 +茶多酚组、顺铂 +硫代硫酸钠组的尿素氮较顺铂组低 (P <0 .0 5 ) ;顺铂 +硫代硫酸钠组较顺铂 +茶多酚组尿素氮、肌酐高。肾脏病理组织学显示 :顺铂致小鼠肾损伤主要表现为肾曲管上皮细胞重度浊肿 ,顺铂 +硫代硫酸钠组均表现为近曲小管上皮细胞中度浊肿 ,顺铂 +茶多酚组肾小球结构较顺铂组完整且清楚 ,近曲小管上皮细胞轻度浊肿。结论 :茶多酚对肾脏有一定的保护作用且效果优于硫代硫酸钠     

姜黄素对顺铂所致大鼠肾毒性的防护作用及其可能机制

目的 顺铂（Cis-diamminedichloroplatinum，CDDP）是当前临床上应用较广泛的一种肿瘤化疗药物。目前，在国内外多种实体瘤治疗中被推荐为首选药物。CDDP却有诸多令人遗憾的毒副作用，特别是肾毒性。CDDP所致肾毒性的确切机制迄今尚不清楚，但大量最新实验研究表明，CDDP诱导氧化应激可能是其机制之一。姜黄素（curcumin，CMN）是中药姜黄（curcumalonga L）中的酚类色素成分，具有抗肿瘤、抗氧化、抗炎等广泛的药理作用，而且毒性很低。有关研究     

山楂酸对顺铂所致大鼠肾毒性的保护作用

目的探讨山楂酸对顺铂急性肾毒性的保护作用及作用机制。方法 40只SD雄性大鼠随机分为对照组(予等剂量生理盐水)、顺铂组(顺铂5 mg·kg^(-1))、山楂酸组(山楂酸40 mg·kg(-1))、山楂酸组(山楂酸40 mg·kg^(-1))、顺铂(5 mg·kg(-1))、顺铂(5 mg·kg^(-1))+低剂量山楂酸(10 mg·kg(-1))+低剂量山楂酸(10 mg·kg^(-1))组、顺铂(5 mg·kg(-1))组、顺铂(5 mg·kg^(-1))+高剂量山楂酸(40 mg·kg(-1))+高剂量山楂酸(40 mg·kg^(-1))组,每组8只。顺铂给药方式为腹腔注射,山楂酸给药方式为经口灌胃,干预组腹腔注射顺铂前1 h经口灌胃给予山楂酸。均每日一次,连续两周。给药两周后,检测尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、血清肌酐(Scr)和尿素氮(BUN)、肾组织丙二醛(MDA)和谷胱甘肽(GSH)含量。结果与对照组相比,顺铂组大鼠血清BUN和Scr、尿NAG酶、肾脏组织MDA含量显著升高,肾组织GSH含量显著下降(均P<0.01)。采用山楂酸干预后,大鼠血清BUN和Scr、尿NAG酶、肾脏组织MDA含量较顺铂组显著下降,GSH含量明显上升(P<0.05或P<0.01)。结论山楂酸对顺铂所致大鼠肾毒性有保护作用,其机制可能与抗氧化有关。     

氨磷汀预防顺铂所致肾毒性

目的观察氨磷汀对顺铂所致肾毒性的预防性保护作用。方法随机将大鼠分成5组,即空白对照组,顺铂5mg·kg-1组,顺铂7.5mg·kg-1组,顺铂5mg·kg-1 氨磷汀200mg·kg-1组和顺铂7.5mg·kg-1 氨磷汀200mg·kg-1组,分别测定肾脏脏器系数、血尿素氮、肌酐水平,并做肾组织病理学检查。结果顺铂5mg·kg-1及7.5mg·kg-1组大鼠BUN、Cr值均明显高于对照组和加用氨磷汀组,差异有显著性(P<0.05或P<0.01);氨磷汀组肾脏脏器系数明显下降,病理分级显示氨磷汀肾损害保护率分别为61.5%和56.8%。结论氨磷汀能有效地预防顺铂所致肾毒性。     

改良水化法对以顺铂为主方案化疗所致肾毒性的影响

目的观察改良肠道水化对顺铂治疗多种恶性肿瘤的肾毒性的影响。方法168例恶性肿瘤患者,其中肺癌98例,乳腺癌36例,食管癌34例。化疗均为含顺铂的联合化疗方案,顺铂量为80~100mg/m2,第1天给药,给药当天静脉输液1000~2000m l,口服补液1500~2500m l,给予积极止吐,并于顺铂后1h给予速尿利尿,化疗前后检测血、尿β2-微球蛋白及肾功能。结果168例患者均顺利完成2个周期的化疗,仅有10例患者出现一过性的微球蛋白及尿素氮升高,与常规静脉输液水化相比未增加肾毒性。结论改良肠道水化方法简便易行,费用低,能较好的预防顺铂的肾毒性,值得临床推广应用。     

水飞蓟宾对顺铂所致大鼠肾毒性的预防作用

观察了大鼠 ig水飞蓟宾 (SB)对顺铂 (CDDP)肾毒性的预防作用及可能机理 ,并初步探讨 SB对CDDP抗肿瘤效应的影响 .大鼠经 ig SB 2 0 0 mg·kg-1后 1 h,ip CDDP5mg· kg-13和 5d后与仅ip CDDP组比较 ,体重和谷胱甘肽过氧化物酶活性明显升高 ,而尿素氮含量 ,尿 N -乙酰 -β- D-氨基葡萄糖苷酶的排泄及丙二醛生成均明显降低 .ig SB30 0 mg· kg-1后 ip CDDP5mg·kg-1对荷 S180 小鼠的瘤重抑制率为 85.7% ,与仅 ip CDDP 5mg· kg-1组的瘤重抑制率 (81 .7% )无明显差别 ,ig SB30 0mg·kg-1组的瘤重抑制率为 30 % .表明 SB明显预防 CDDP所致大鼠肾毒性 ,但不影响 CDDP抗肿瘤作用 . SB预防肾毒性的部分机理可能与清除自由基 ,抑制脂质过氧化形成 ,并提高机体抗氧化能力有关 .SB对 CDDP抑制小鼠 S180 生长的效能没有明显影响     

葡甲胺对顺铂所致大鼠肾毒性的预防作用

目的　研究葡甲胺 (N MG)对顺铂 (CDDP)所致大鼠肾毒性的预防作用及其可能机制。方法　大鼠1次腹腔注射 5mg/kgCDDP动物模型 ,于CDDP处理前 1h经口给予N MG预处理。检测指标包括血尿素氮BUN、尿蛋白、尿铂 (Pt) ,肾组织匀浆中NOS、NO、MDA、SOD及肾组织Pt含量 ,同时观察抗肿瘤活性。结果　给药后第 3、5天N MG预处理组可明显预防CDDP所致大鼠肾功能损害 ,降低肾组织中NOS、NO、及MDA含量 ,增加SOD活性 (P <0 0 5或P <0 0 1)。另外 ,给药后第 3天尿Pt(0 .42 5 μg/mgCr)排泄量非常显著地高于CDDP组(0 2 45 μg/mgCr,P <0 0 1) ,肾组织Pt含量于给药后第 3、5天显著低于CDDP组 (P <0 0 5 )。N MG预处理对荷瘤小鼠的肿瘤抑制率与CDDP组无显著性差异。结论　N MG预处理能明显预防CDDP所致大鼠的肾损害 ,其预防作用机制可能是N MG促进Pt经尿排出 ,并减少了肾组织Pt蓄积 ,从而CDDP产生的自由基减少 ,脂质过氧化程度减轻。N MG对CDDP抗肿瘤活性无明显影响。     

顺铂肾毒性的防治措施

顺铂肾毒性的防治措施１０００３９军事医学科学院附属医院药理室梁月琴综述郭军华张秀国审校顺铭是１９６５年Ｒｏｓｅｎｂｅｒｇ等’“发明的抗肿瘤药物，它对卵巢癌、肺癌、膀优癌、乳腺癌、头颈部肿瘤和星丸肿瘤有极好的治疗作用，但顺铂易引起严重的肾毒性，且肾毒性...     

虎杖苷对肾纤维化模型大鼠肾组织中MMP-9和TIMP-1蛋白表达的影响

目的:考察虎杖苷对肾纤维化模型大鼠肾组织中基质金属蛋白酶9(MMP-9)和基质金属蛋白酶组织抑制物1(TIMP-1)蛋白表达的影响,探讨其延缓大鼠肾纤维化的作用机制。方法:将40只大鼠随机分为假手术组(生理盐水)、模型组(生理盐水)、虎杖苷组(100 mg/kg)和贝那普利组(阳性对照,5 mg/kg)。除假手术组外,其余各组大鼠均采用单侧输尿管梗阻法制备肾纤维化大鼠模型。术后1 h,各组大鼠灌胃相应药物,每天给药1次。连续给药4周后,检测各组大鼠尿液中β_2微球蛋白(β_2-MG)、N-乙酰-β-D-氨基葡萄糖苷酶(NAG)含量和血清中尿素氮(BUN)、肌酐(Cr)含量;苏木素-伊红染色观察大鼠肾组织病理改变,并进行评分;免疫组织化学法检测大鼠肾组织中MMP-9和TIMP-1蛋白表达。结果:与假手术组比较,模型组大鼠尿液中β_2-MG、NAG含量和血清中BUN、Cr含量均显著升高(P<0.05),并且大鼠肾组织的病理评分和组织中MMP-9、TIMP-1蛋白的表达水平也显著升高(P<0.01)。与模型组比较,虎杖苷组和贝那普利组大鼠肾组织中MMP-9蛋白表达水平持续增高(P<0.01),其余各指标水平均显著降低(P<0.05或P<0.01);且虎杖苷组与贝那普利组比较大鼠各指标水平差异均无统计学意义(P>0.05)。结论:虎杖苷延缓大鼠肾纤维化进程的机制可能与上调大鼠肾组织中MMP-9蛋白表达和下调TIMP-1蛋白表达,升高MMP-9/TIMP-1的比值有关。     

Effects of Disopyramide and Verapamil on Renal Disposition and Nephrotoxicity of Cisplatin in Rats

Purpose. The purpose of this study was to determine the effects of disopyramide and verapamil on the renal handling of cisplatin (CDDP) and nephrotoxicity in rats. The stereoselective effect of verapamil was also studied. Methods. CDDP was administered to rats by i.v. bolus injection or by infusion at a constant rate with or without concomitant administration of racemic disopyramide, racemic verapamil, or each verapamil enantiomer. The concentrations of CDDP in plasma and in the kidney and liver were determined by HPLC. In separate experiments, CDDP was administered as described above, and blood urea nitrogen (BUN) was monitored for 7 days. Results. The BUN level after administration of CDDP was significantly reduced by coadministration of either disopyramide or verapamil. Renal accumulation of CDDP was significantly reduced by these drugs, whereas accumulation into the liver was not significantly changed. The relationship between the BUN levels and the area under the curve of CDDP concentration in the kidney versus time (AUC_k) was analyzed using a sigmoid E_max model; this showed that the reduced BUN levels were explained by the AUC_k. Furthermore, verapamil showed stereoselective inhibition of the renal accumulation of CDDP. Conclusions. The renal accumulation of CDDP was inhibited by disopyramide and verapamil, and this inhibition resulted in the amelioration of nephrotoxicity.     

奥美拉唑对顺铂致大鼠胃损伤的保护作用研究

目的:研究奥美拉唑对顺铂致大鼠胃损伤的保护机制。方法:取大鼠随机分为正常对照组、模型组和奥美拉唑低、中、高剂量(10、20、40mg.kg-1)组,每组9只,后4组腹腔注射顺铂0.1mg.g-1进行化疗,奥美拉唑各剂量组于化疗前30min尾静脉注射相应药物。化疗6h后,检测各组大鼠胃液的pH值、胃液和胃组织中顺铂的含量,并进行胃组织病理学观察。结果:正常对照组胃液pH值为2.7±0.35,与其比较,模型组胃液pH值明显降低,胃组织损伤严重(P<0.05);与模型组比较,奥美拉唑各剂量组胃液的pH值明显升高,顺铂含量明显减少(P<0.05或P<0.01),但胃组织中顺铂含量无明显变化,胃组织损伤明显减轻(P<0.05),且与剂量呈正相关,但各剂量组间差异无统计学意义。结论:奥美拉唑对顺铂致胃损伤具有一定的保护作用,可能是通过降低胃液pH值和减少胃液中顺铂含量来实现的;且在一定范围内,奥美拉唑的保护作用与剂量呈正相关。     

七叶皂苷钠对大鼠大脑中动脉梗死后基质金属蛋白酶-9表达的影响

目的探讨七叶皂苷钠对大鼠大脑中动脉梗死后基质金属蛋白酶-9(MMP-9)表达的影响。方法60只雄性W istar大鼠随机分为对照组20只、小剂量七叶皂苷钠治疗组20只和大剂量七叶皂苷钠治疗组20只。治疗组分别于梗死后6h、24h、48h及96h干预,每个时间点5只大鼠,采用免疫组化和原位杂交法分别测定大鼠大脑中动脉梗死后MMP-9蛋白及其mRNA。结果小剂量治疗组和大剂量治疗组MMP-9蛋白及其mRNA表达均低于对照组,差异有统计学意义(P<0.05),大剂量治疗组MMP-9蛋白及其mRNA表达均低于对应时间点小剂量治疗组,差异有统计学意义(P<0.05)。结论七叶皂苷钠可阻断大鼠大脑中动脉梗死后MMP-9及其mRNA表达,并且有量效关系。     

Amelioration of Cisplatin Nephrotoxicity with Glycine: Dose Dependency in Rats

The effects of glycine (0·1-1·0 g μg kg^?1, i.v.) on the acute changes in renal haemodynamics and nephrotoxicity produced by cisplatin (6·0 mg g kg^?1, i.v.) were investigated in the rat. Cisplatin produced decreases of 50% in the clearance of [³H] inulin (C_IN) and renal blood flow (RBF), 110 min following its injection. Glycine at a dose of 0·1 g kg^?1 produced no attenuation of the cisplatin-induced decrease in C_IN or RBF. Furthermore, this dose of glycine provided no significant protection of renal function over a 7-day period following cisplatin injection. By contrast, glycine at a dose of either 0·5 or 1·0 g kg^?1 markedly attenuated cisplatin-induced falls in C_IN and RBF, with the highest dose completely preventing any falls in these indices during the course of the experiment. Treatment with these higher doses of glycine produced prominent protection from the nephrotoxic actions of cisplatin, as evidenced by improvements in a range of indices of renal function which included plasma urea and creatinine concentrations, urine output, sodium excretion, C_IN and the clearance of [¹⁴C]P-aminohippurate. The results of experiments with an intermediate dose of 0·25 g kg^?1 glycine revealed some degree of amelioration of acute renal haemodynamic effects of cisplatin, particularly with regard to C_IN; whilst in the nephrotoxicity study, 0·25 g kg^?1 glycine produced a modest but significant reduction in cisplatin-induced acute renal dysfunction. The results have revealed a clear association between the acute renal haemodynamic effects produced by glycine in cisplatin-injected rats with the longer-term renal protective effects of glycine in cisplatin nephrotoxicity. The findings indicate that glycine's ability to prevent the falls in RBF and glomerular filtration rate produced by cisplatin plays an important role in the protective effect of glycine in cisplatin-induced nephrotoxicity.     

罗格列酮对糖尿病大鼠血清MMP-9及外周血单核细胞MMP-9mRNA表达的影响

目的：观察过氧化物酶体增殖物激活受体γ（PPARγ）配体罗格列酮对糖尿病大鼠血清基质金属蛋白酶9（MMP-9）浓度和外周血单核细胞mRNA表达的影响。方法：30只SD大鼠随机分为三组，对照组、糖尿病组和罗格列酮组，每组10只。糖尿病组和罗格列酮组腹腔注射链脲霉素制作糖尿病大鼠模型后，罗格列酮组以罗格列酮灌胃，5mg·kg^-1·d^-1，共28d，对照组和糖尿病组以等量0.9％氯化钠溶液灌胃，比较治疗前、后的血清MMP-9浓度的变化，分离外周血单核细胞，RT-PCR检测MMP-9mRNA的变化。结果：处理28d后血清MMP-9浓度明显降低（P〈0.01），外周血单核细胞MMP-9mRNA表达量明显降低。结论：罗格列酮可以降低糖尿病大鼠血清MMP-9及外周血单核细胞MMP-9mRNA袁达．提示冀可能通过抑制MMP-9表达稳定动脉粥样锺化斑块．     

Attenuation of Cisplatin Nephrotoxicity by Streptozotocin-Induced Diabetes

Attenuation of Cisplatin Nephrotoxicity by Streptozotocin-InducedDiabetes. SCOTT, L. A., MADAN, E., AND VALENTOVIC, M. A. (1989).Fundam. Appl. Toxicol 12, 530–539. The thera peutic useof cisplatin is associated with acute renal failure. The purposeof this study was to determine (a) if streptozotocin (STZ) wastoxic to renal proximal tubules and (b) the nephrotox icityof cisplatin in STZ-diabetic rats. Male Sprague-Dawley ratswere injected with STZ (55 mg/kg, ip) to induce a diabetic state.BUN and renal cortical slice uptake of p-aminohippurate (PAN)and tetraethylammonium (TEA) were not altered, relative to normoglycemicrats, 3, 16, and 28 days following STZ treatment. These resultsindicate that STZ is not toxic to renal proximal tubules. Cisplatinnephrotoxicity studies were then conducted in STZ-diabetic andnormo glycemic rats. Cisplatin nephrotoxicity was also evaluatedin diabetic rats pretreated for 8 days with insulin. Diabeticand normoglycemic rats were administered 5 mg/kg cisplatin orwater (ip). Increased kidney weight, BUN levels, glucosuna,and proteinuria were measured in normoglycemic rats 4 days aftercisplatin administration. Renal cortical TEA and lactate-stimulatedPAH uptake (p<0.05) were diminished in the normoglycemicrats 4 days after cisplatin injection. No change in kidney weight,BUN levels, or renal cortical slice accumulation of PAH andTEA was observed in diabetic rats treated with cisplatin. However,cisplatin administration to diabetic rats pretreated with insulinresulted in increased mortality, proteinurla, glucosuna andelevated kidney weight. These results indicate that the diabeticstate attenuates cisplatin nephro toxicity. Additionally, theseresults indicate that diabetes attenuation ofcisplatin nephrotoxicityis dependent on the severity of the diabetic state.     

维生素E 对顺铂所致的小鼠肾毒性的影响及其机制研究

目的观察维生素E对抗癌药物顺铂致小鼠肾毒性的影响及其可能机制。方法采用10mg.kg-1顺铂腹腔注射诱导小鼠肾脏损伤,48小时后分别予维生素E250mg.kg-1和500mg.kg-1口服灌胃,顺铂诱导72小时后通过检测小鼠血清尿素氮和肌酐水平评价肾功能的变化,检测肾组织中丙二醛(malonaldehyde,MDA)含量,过氧化物歧化酶(super oxide dismutase,SOD)、过氧化氢酶(catalase,CAT)、还原型谷胱甘肽(reduce glutathione,GSH)和谷胱甘肽过氧化物酶(glutathion peroxidase,GPX)活性的变化,以评价小鼠肾组织氧化应激水平。结果与正常小鼠相比,10mg.kg-1顺铂诱导的小鼠血清尿素氮、肌酐水平和肾组织MDA水平均显著升高(P<0.01),而肾组织SOD、CAT、GSH、GPX的活性均显著降低(P<0.01);与10mg.kg-1顺铂诱导的小鼠相比,250mg.kg-1和500mg.kg-1维生素E灌胃的小鼠血清尿素氮、肌酐水平和肾组织MDA水平均显著降低(P<0.01),250mg.kg-1维生素E灌胃的小鼠肾组织GPX的活性显著升高(P<0.01),500mg.kg-1维生素E灌胃的小鼠肾组织CAT和GPX的活性均显著升高(P<0.01),而三组之间肾组织SOD活性的差异无统计学意义(P>0.05)。结论高剂量的维生素E可以有效改善顺铂诱导的小鼠肾功能,可能与其降低肾组织的氧化应激有关。     

Nebivolol Ameliorates Cisplatin‐Induced Nephrotoxicity in Rats

Treatment with cisplatin is associated with dose‐limiting side effects, mainly nephrotoxicity. On the other hand, nebivolol, a β₁‐adrenoceptor antagonist, exhibits vasodilatory and antioxidative properties. This study aimed to determine whether nebivolol possesses a protective effect against cisplatin nephrotoxicity and explore many mechanisms underlying this potential effect. Nephrotoxicity was induced in Wistar rats by a single intraperitoneal injection of cisplatin (6 mg/kg) on day 2. Nebivolol (10 mg/kg) was administered orally for 7 consecutive days. Nebivolol showed a nephroprotective effect as demonstrated by the significant reduction in the elevated levels of serum creatinine and urea as well as renal levels of malondialdehyde, nitric oxide products (nitrite/nitrate), inducible nitric oxide synthase, tumour necrosis factor‐alpha, caspase‐3, angiotensin II and endothelin‐1 with a concurrent increase in renal levels of reduced glutathione and endothelial nitric oxide synthase compared to untreated rats. Histopathological examination confirmed the nephroprotective effect of nebivolol. Pre‐treatment with N_ω‐nitro‐L‐arginine methyl ester, the non‐specific nitric oxide synthase inhibitor, partially altered the protection afforded by nebivolol. In conclusion, nebivolol protects rats against cisplatin‐induced nephrotoxicity that is most likely through its antioxidant, anti‐inflammatory and antiapoptotic effects as well as by abrogation of the augmented angiotensin II and endothelin‐1 levels.     

The Protective Effects of Acetylsalicylic Acid on Free Radical Production in Cisplatin Induced Nephrotoxicity: An Experimental Rat Model

Abstract

Cisplatin-induced nephrotoxicity is closely associated with an increase in lipid peroxidation. In several previous reports it was claimed that acetylsalicylic acid (ASA) shows its therapeutic potential as a free radical scavenger. The aim of the study was to investigate effects of ASA on cisplatin induced nephrotoxicity in an experimental rat model. Control animals (n:7) were administered 1 mL saline solution intraperitoneal (i.p.). Cisplatin group (n:7) was treated with a single dose of cisplatin i.p. (6 mg/kg), ASA group (n:7) was treated with i.p. (2.5 mg/kg) per day during the study, cisplatin plus ASA group (n:7) was administered single dose cisplatin i.p. (6 mg/kg) plus ASA (2.5 mg/kg) during 5 days. At the end of the study, Catalase (CAT), Glutathione Peroxidase (GSH-Px), Superoxide Dismutase (SOD), Nitric Oxide Synthase (NOS) enzymes activities and Malondialdehyde (MDA), Antioxidant Potential (AOP) levels were measured in both erythrocytes and renal tissues. Urea and creatinine levels and renal tissue necrosis in cisplatin plus ASA group were significantly lower than cisplatin group (p = 0.000, p = 0.014, p = 0.015). SODr activities and MDAr levels of cisplatin plus ASA group were also significantly lower than cisplatin group (p = 0.000, p = 0.029). These results show that cisplatin and ASA combination decreases the levels of urea and creatinine, reduces necrosis and improves antioxidant enzyme activities, MDA and AOP in rat kidney.     

Dose Response of Carboplatin‐Induced Nephrotoxicity in Rats

Abstract: Carboplatin, a second‐generation platinum‐containing anticancer drug, is currently being used against a variety of cancers. High‐dose carboplatin chemotherapy can cause renal tubular injury in cancer patients. However, the biochemical mechanism of carboplatin‐induced renal injury has not been well studied. This study investigated the dose response of carboplatin‐induced changes in endogenous antioxidants, lipid peroxidation and platinum content in rat kidney. Male Wistar rats (250–300 g) were divided into five groups and treated as follows: (1) control (saline, intraperitoneally); (2) carboplatin (64 mg/kg, intraperitoneally); (3) carboplatin (128 mg/kg, intraperitoneally); (4) carboplatin (192 mg/kg, intraperitoneally); and (5) carboplatin (256 mg/kg, intraperitoneally). The animals were sacrificed four days after treatment. The blood and kidneys were isolated and analyzed. Plasma creatinine and blood urea nitrogen levels were increased significantly in response to carboplatin in a dose‐dependent manner. Renal superoxide dismutase and catalase activities were decreased significantly due to carboplatin at dosages of 128 mg/kg and above. The protein expressions of renal copper/zinc‐superoxide dismutase and manganese‐superoxide dismutase significantly depleted after carboplatin. Carboplatin (192 and 256 mg/kg) significantly increased lipid peroxidation (malondialdehyde concentration) in rat kidneys. Carboplatin dose‐dependently increased the renal platinum concentration, with significance at dosages of 128 mg/kg and above. Carboplatin (256 mg/kg) significantly increased renal xanthine oxidase activity, while ratio of reduced to oxidized glutathione depleted significantly. The data suggested that carboplatin caused dose‐dependent oxidative renal injury, as evidenced by renal antioxidant depletion, enhanced lipid peroxidation, platinum content, plasma creatinine and blood urea nitrogen levels in rats.