灯盏花素对顺铂肾损害的防治及抗氧化的实验

目的观察灯盏花素对小鼠顺铂（cisplatin,DDP）肾损害的防治及抗氧化作用,探究其可能的作用机制。方法以 DDP 8 mg/kg单次腹腔注射制备小鼠肾脏损害模型,再以不同剂量的灯盏花素灌胃,1次/天,连续给药7 d后采样,观察肾脏结构变化,检测血清中肌酐（Scr）、尿素氮（BUN）、丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性,肾皮质 SOD 及 MDA 的变化。 结果灯盏花素可明显改善顺铂肾损害的小鼠肾脏结构,降低血清Scr、BUN及肾皮质 MDA含量（P<0.05,P<0.01）,而 SOD 活性明显升高（P<0.05）。 结论灯盏花素可明显减轻顺铂引起的肾毒性,其机制可能与抑制顺铂肾损害所致血液和肾皮质脂质过氧化反应增强有关。     

氨磷汀对顺铂肾毒性损伤的保护作用及其机制的研究

目的 观察顺铂的肾毒性损伤部位、形式与肾功能检查结果的相关性,以了解细胞凋亡的发生机制和氨磷汀的保护机制是否与肾组织Fas和FasL表达改变有关。方法 随机将大鼠分成3组,即对照组（生理盐水）、顺铂组（6mg／kg）和氨磷汀组（顺铂6mg／kg＋氨磷汀200mg／kg）,取其血清标本和肾组织,分别做血清BUN、Cr检测和肾组织病理学检查,并用原位缺口末端标记法（TUNEL）做肾组织凋亡细胞检测、Fas和FasL免疫组化染色,再用图像分析软件对其做阳性细胞计数和染色总灰度值测定。结果 顺铂组动物血清BUN、Cr值均明显高于对照组和氨磷汀保护组,3d时,差异已有统计学意义（P〈0．05）;5d时,两者差异分别为P〈0．01和P〈0．05;10d时,恢复正常。顺铂组肾小管上皮细胞坏死和凋亡均很严重,其凋亡细胞计数明显高于对照组和氨磷汀组（P值均〈0．01）,肾组织Fas和FasL表达的总灰度值,明显高于对照组和氨磷汀组（P值均〈0．01）。结论 氨磷汀对顺铂的肾毒性损伤有保护作用,其机制可能与抑制肾组织Fas和FasL的表达有关。     

硫普罗宁减轻顺铂肾毒性的临床观察

目的 研究硫普罗宁对顺铂所致肾毒性的减轻作用。方法 将病理证实的40例肿瘤患者随机分成两组,应用含顺铂为主的联合方案化疗。治疗组20例,化疗前1小时内静滴硫普罗宁0.2g/m²,随后给予大剂量顺铂（80～120mg/m²）化疗;对照组20例,仅给予大剂量顺铂（80～120mg/m²）化疗。比较两者化疗前后血BuN,血Cr,尿β₂MG的变化。结果 化疗第七天血BuN值治疗组较对照组差异有统计学意义（P<0.05）,化疗后第3天,尿β₂MG治疗组较对照组差异有统计学意义（P<0.01）。结论 硫普罗宁能减轻顺铂所致肾毒性。     

NS-398协同顺铂作用人肺腺癌差异蛋白质组分析

背景与目的 实验证明一种高度选择性的COX-2抑制剂--NS-398能增强传统化疗药物顺铂对肺腺癌细胞的生长抑制作用,但其机制尚不清楚.本研究的目的是探讨NS-398与顺铂协同抑制肺腺癌细胞增殖的作用机制.方法 采用二维聚丙烯酰胺凝胶电泳分离NS-398和顺铂作用下肺腺癌细胞的蛋白质,质谱分析法(MALDI-TOF-MS)和数据库查询鉴定其中部分差异蛋白质.结果 NS-398与顺铂联合组表达量下调的差异蛋白点22个,表达量上调蛋白点2个.选择其中17个表达量下调蛋白点、2个表达量上调蛋白点进行质谱鉴定,初步鉴定了NS-398与顺铂联合组6个表达下调的差异蛋白质,其中部分为细胞骨架蛋白,部分为与细胞增殖和凋亡相关的蛋白,部分为细胞代谢途径相关酶.结论 热休克蛋白90和磷酸丙糖异构酶可能参与了NS-398和顺铂对肺腺癌细胞增殖的协同抑制作用.     

大剂量顺铂为主方案治疗肺癌中的肾功能监测

目的：探讨顺铂（DDP）化疗中肾毒性的监测方法。方法：动态观察61例肺癌患者接受含大剂量DDP（80－120mg/m^2)联合化疗114个周期的血清尿素氮（BUN）、肌酐（Cr)，以及尿β2－微球蛋白（β2－MG）、尿α1－微球蛋白（α1－MG）、尿白蛋白（Alb)、尿转铁蛋白（TRF）和尿维生素A1结合蛋白（RBP）等指标，筛选出能早期监测顺铂肾毒性的指标。结果：（1）化疗早期（第1－5天）尿β2－MG和α1－MG异常率明显高于其它指标（P＜0．001）；（2）血清BUN和Cr异常率于化疗后期（第10天）增高明显；（3）化疗后期血清BUN和Cr异常者在化疗早期均有尿β2－MG和／或α1－MG异常。结论：在含DDP的肺癌联合化疗中，尿β2－MG和α1－MG具有肾毒性的早期诊断价值。     

香加皮三萜类化合物对实验性大鼠食管癌的阻断作用及机制

目的探讨中药香加皮提取物三萜类化合物（TCCP）对甲基苄基亚硝胺（NMBA）诱导F344大鼠食管癌前病变形成的阻断作用及其机制。方法健康雄性F344大鼠90只,随机分为模型组、TCCP干预组、大豆油对照组和正常对照组。模型组大鼠皮下注射0.5 mg/kg NMBA,TCCP干预组大鼠同时给予0.5 mg/kg NMBA皮下注射及香加皮三萜类化合物20 mg/kg肌肉注每周给药3次,连续5周;大豆油对照组大鼠肌注大豆油1 ml/kg,正常对照组大鼠常规饲养。分别在给药后第9、15和25周,麻醉后解剖大鼠,HE染色后光镜下观察食管上皮组织病理学变化;用Western blot法检测GSK-3β和β-catenin蛋白表达水平;用RT-PCR法检测c-myc mRNA表达水平。结果(1)正常对照组及大豆油对照组在整个实验过程中未发现食管异常变化,模型组大鼠随诱癌时间延长食管病变逐渐加重。TCCP干预可缓解食管上皮的病变。(2)正常大鼠食管上皮中有少量β-catenin蛋白表达,模型组大鼠食管上皮β-catenin蛋白表达显著增强（P<0.05）;正常大鼠食管上皮GSK-3β的蛋白表达丰富,随着诱癌时间延长表达水平逐渐降低;与模型组相比,在诱癌9、15和25周时TCCP干预组大鼠食管上皮组织中β-catenin蛋白表达水平均显著下降（P<0.05）;而GSK3β蛋白表达显著升高（P<0.05）。(3)与正常对照组相比,各时间点模型组大鼠食管上皮c-myc mRNA表达水平均显著升高。与模型组相比,在诱癌9、15周时TCCP干预组大鼠食管上皮组织中c-myc mRNA表达水平均显著下降,而诱癌25周时差异无统计学意义（P>0.05）。结论TCCP可能通过促进Wnt信号分子GSK-3β的表达,抑制β-catenin蛋白的表达,进而下调下游靶基因c-myc的转录,干扰细胞周期转化,逆转细胞的分化,可能是其抑制食管癌变细胞生长机制之一。     

肠道微生态对非小细胞肺癌小鼠抗肿瘤作用影响的机制研究

目的:探讨肠道微生态平衡抗非小细胞肺癌作用的免疫机制。方法:建立C57BL/6J小鼠Lewis肺癌模型72只,根据腹腔注射药物不同分为对照组、顺铂组、顺铂/抗生素组、顺铂/乳酸杆菌组,每组18只。记录各组小鼠肿瘤体积、存活时间;采用Western Blot法检测瘤体VEGFA、Ras、CDKNIB、Bax蛋白表达,EILSA检测血清IL-6、IL-10、TNF-α、IFN-γ水平,PCR检测小鼠肠道菌群数量。结果:与对照组相比,其他组小鼠的肿瘤生长均受到明显抑制。其中,以顺铂/乳酸杆菌组抑瘤作用最明显,顺铂/抗生素组抑制效果最差。与顺铂/乳酸杆菌组相比,顺铂组与顺铂/抗生素组的生存时间明显更短。与对照组相比,顺铂组小鼠致癌基因VEGFA、Ras的表达水平分别降低了47.9%、33.2%,抑癌基因Bax、CDKNIB的表达水平分别上调了121.7%、128.9%。与顺铂组对比,抗生素减弱了顺铂对VEGFA的下调及对CDKNIB、Bax的上调作用。相反地,乳酸杆菌明显增强了顺铂对VEGFA水平的下调及对CDKNIB的上调作用。ELISA检测结果发现,与顺铂/抗生素组比较,顺铂/乳酸杆菌组IL-6、IFN-γ水平显著升高,IL-10水平显著降低（P<0.05）,但TNF-α无明显差异（P>0.05）。与对照组相比,顺铂组小鼠4种菌群数量均呈现下降趋势,但差异无统计学意义（P>0.05）,顺铂/抗生素组4种菌群数量下降最为明显（P<0.05）,顺铂/乳酸杆菌组菌群数量与对照组基本接近。结论:肠道微生态平衡有助于抗肺癌作用,能增强顺铂的抗肿瘤效应。     

阿霉素大鼠肾病模型足细胞线粒体体视学分析

目的探讨大鼠肾脏中足细胞线粒体形态和数目与阿霉素大鼠肾病模型蛋白尿的关系。方法清洁级雄性SD30只大鼠尾静脉分别注射阿霉素0．7mg／100g体重和生理盐水，分别在注射后2W（对照组3只，阿霉素组3只）、4w（对照组3只，阿霉素组6只）和6W（对照组8只，阿霉素组7只）处死大鼠，取肾皮质标本进行透射电镜观察，对线粒体形态和密度进行体视学分析。结果阿霉素组大鼠4W出现蛋白尿，持续至6W。对照组大鼠肾组织足细胞内线粒体多呈椭圆形，阿霉素组大鼠足细胞线粒体形态多样，大小不一。统计分析未发现阿霉素组和对照组大鼠足细胞线粒体面积、周长、形状因子和最大长宽比的差异。注射2W后蛋白尿出现前，阿霉素组大鼠肾组织足细胞内线粒体面数密度明显增多，与对照组比较差异具有统计学意义（0．17±0．00VS．0．14±0．01，t=6．173，P〈0．01），同时线粒体相对于细胞体的表面积密度有增加趋势（0．78±O．03VS．0．71±0．04，t=-2．526，P=0．065）。注射6w后，阿霉素组大鼠足细胞线粒体面数密度无显著变化，线粒体相对于足细胞胞浆的表面积密度显著减少（0．71±0．11VS．0．87±0．12，P=0．02）。结论线粒体多形性改变参与阿霉素大鼠肾病模型蛋白尿的发生，足细胞线粒体数量增多是阿霉素大鼠肾病模型蛋白尿发生过程中的早发事件，线粒体膜表面积密度下降参与足细胞损伤及阿霉素大鼠肾病的进展。     

顺铂联合补中益气汤对A549/DDP荷瘤裸鼠移植瘤survivin蛋白表达的影响

目的 探讨顺铂联合补中益气汤对A549/DDP荷瘤裸鼠移植瘤survivin蛋白表达的影响。方法 30只BALB/c-nu裸小鼠随机分为5组,A：荷瘤对照组、B：顺铂组、C：顺铂联合低剂量补中益气汤组、D：顺铂联合中剂量补中益气汤组、E：顺铂联合高剂量补中益气汤组。25 d后处死全部裸小鼠。测量移植瘤体积、重量并计算药物抑瘤率;Real-time PCR法检测移植瘤组织survivin mRNA的表达;Western blot法检测移植瘤组织survivin蛋白的表达。结果 顺铂联合低、中、高剂量组均较荷瘤对照组、顺铂组移植瘤体积显著缩小,重量显著减轻,差异有统计学意义;顺铂抑瘤率随着补中益气汤的剂量增加而增大;顺铂组、顺铂联合低剂量组较荷瘤对照组移植瘤组织中survivin的基因和蛋白表达上调,而顺铂联合中、高剂量组较荷瘤对照组survivin的基因和蛋白表达下调,差异均有统计学意义;顺铂联合低、中、高剂量补中益气汤组较顺铂组移植瘤组织中survivin的基因和蛋白表达均下调,差异均有统计学意义。结论 顺铂联合补中益气汤可通过下调survivin的表达改善A549/DDP荷瘤裸鼠移植瘤对顺铂的耐药性。     

人肺腺癌细胞耐顺铂株A549/CDDP的比较蛋白质组学研究

背景与目的 化疗是肺癌综合治疗的重要部分,但是肿瘤细胞耐药常导致化疗失败.本研究采用蛋白组学方法研究人肺腺癌细胞A549对顺铂产生耐药性前后的蛋白表达差异,筛选有价值的靶位.方法 以顺铂为诱导药物,人肺腺癌细胞系A549为诱导对象,采用逐步增加剂量与大剂量冲击相结合的方法,诱导建立耐顺铂细胞株A549/CDDP.对A549与A549/CDDP进行蛋白组学研究,即利用双向凝胶电泳(2-DE)分离两组总蛋白后,通过图像分析寻找表达差异的蛋白,对其进行MALDI-TOF质谱分析.结果 比较两者2-DE图谱,得到差异蛋白点82个;对其中6个差异蛋白点进行肽质量指纹图分析,鉴定出葡萄糖调节蛋白75、核糖体蛋白S4、线粒体F1-ATP合酶β亚单位、免疫球蛋白重链可变区;以上差异蛋白均在耐药株中过表达,而在对照组细胞中表达下调或不表达.结论 所鉴定的差异蛋白将为阐明肺癌细胞对顺铂耐药性产生的机制提供线索,也为筛选具体潜在价值的肺癌化疗靶位提供理论依据.     

Methimazole as a protectant against cisplatin-induced nephrotoxicity using the dog as a model

The protective effect of methimazole, a commonly used antithyroid drug, on cisplatin-induced nephrotoxicity was studied. Eight dogs received 80 mg/m² cisplatin i.v. without saline prehydration. Dogs were randomized into two groups of four dogs each: one group received 40 mg/kg methimazole i.p. at 30 min prior to and 4 h after cisplatin delivery, and the other group received saline placebo i.p. Methimazole protected dogs against the in vivo nephrotoxicity elicited by cisplatin as evidenced by clinicopathologic and histopathologic indices. Protection was not complete, as methimazole-treated animals developed mild histopathologic renal changes. Measures of renal oxidative stress did not differ between the two groups at day 5 following cisplating treatment. No difference was noted for serum thyroxine concentrations before or after therapy in either group; however, serum levels of 3,5,3-triiodothyronine were significantly higher on day 5 in both groups of dogs receiving cisplatin, regardless of whether they received methimazole or not. Methimazole as used in this study was found to be well tolerated in dogs over the short term, with no significant clinical or clinicopathologic toxicity being observed. The results of this study support the additional evaluation of methimazole as a protectant against cisplatin-induced nephrotoxicity using the dog as a model.This work was supported in part by Bristol-Myers Squibb Co. (Evansville, Ind.)     

Hydroxyl radical scavenger ameliorates cisplatin-induced nephrotoxicity by preventing oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria

Nephrotoxicity is the major dose-limiting factor of cisplatin chemotherapy. Reactive oxygen species generated in mitochondria are thought to be the main cause of cellular damage in such injury. The present study examined, in vivo, the protective potential of the hydroxyl radical scavenger dimethylthiourea (DMTU) against cisplatin-induced effects on renal mitochondrial bioenergetics, redox state and oxidative stress. Adult male Wistar rats (200 to 220 g) were divided into four groups of eight animals each. The control group was treated only with an intraperitoneal (i.p.) injection of saline solution (1 ml/100 g body weight). The second group was given only DMTU (500 mg/kg body weight, i.p, followed by 125 mg/Kg, i.p., twice a day until they were killed). The third group was given a single injection of cisplatin (10 mg/kg body weight, i.p.). The fourth group was given DMTU (500 mg/kg body weight, i.p.), just before the cisplatin injection (10 mg/kg body weight, i.p.), followed by injections of DMTU (125 mg/kg body weight, i.p.) twice a day until they were killed. Animals were killed 72 h after the treatment. Besides not presenting any direct effect on mitochondria, DMTU substantially inhibited cisplatin-induced mitochondrial injury and cellular death by apoptosis, suppressing the occurrence of acute renal failure. All the following cisplatin-induced effects were prevented by DMTU: (1) increased plasmatic levels of creatinine and blood urea nitrogen (BUN); (2) decreased ATP content, calcium uptake and electrochemical potential; (3) oxidation of lipids, including cardiolipin; and oxidation of proteins, including sulfhydryl, and aconitase enzyme, as well as accumulation of carbonyl proteins; (4) depletion of the antioxidant defense (NADPH and GSH) and (5) increased activity of the apoptosis executioner caspase-3. Our findings show the important role played by mitochondria and hydroxyl radicals in cisplatin-induced nephrotoxicity, as well as the effectiveness of DMTU in preventing the renal mitochondrial damage caused by cisplatin. These results strongly suggest that protection of mitochondria by hydroxyl radical scavengers may be an interesting approach to prevent the kidney tissue damage caused by cisplatin-chemotherapy.     

Regulation of PUMA-alpha by p53 in cisplatin-induced renal cell apoptosis

Nephrotoxicity is a major side effect of cisplatin, a widely used cancer therapy drug. Depending on its concentration, cisplatin induces necrosis or apoptosis of tubular cells in the kidneys, whereas the underlying injury mechanism is unclear. Our recent work has suggested a critical role for p53 in cisplatin-induced tubular cell apoptosis; nevertheless, the apoptotic events triggered by p53 remain elusive. The current study has examined Bcl-2 family proteins, critical regulators of apoptosis that may be subjected to p53 regulation. Following cisplatin treatment, the expression of Bcl-xL, an antiapoptotic molecule, was suppressed, while the expression of Bak, a proapoptotic molecule, increased slightly. Of interest, PUMA-alpha, a newly identified p53-responsive proapoptotic Bcl-2 family protein, was drastically induced by cisplatin. PUMA-alpha induction preceded or paralleled the development of apoptosis. Induced PUMA-alpha was localized in mitochondria and appeared to antagonize Bcl-xL via molecular interaction. PUMA-alpha induction during cisplatin treatment was attenuated by pifithrin-alpha, a pharmacological inhibitor of p53, which was accompanied by the amelioration of Bax activation, cytochrome c release and apoptosis. Moreover, PUMA-alpha induction was suppressed by dominant-negative p53. Importantly, cisplatin-induced apoptosis was ameliorated in PUMA-alpha knockout cells. In vivo, cisplatin induced PUMA-alpha in the kidneys, and the inductive response was abrogated in p53-deficient animals. Together, this study has demonstrated the first compelling evidence for the involvement of PUMA-alpha in p53-mediated renal cell apoptosis during cisplatin nephrotoxicity.     

Studies on adequate intervals of cisplatin administration to ameliorate cisplatin-induced nephrotoxicity

Experimental studies were designed in order to ameliorate cisplatin-induced nephrotoxicity. Cisplatin was injected intravenously into DS mice at a dose of 5.0 mg/kg. Plasma platinum levels declined in a biphasic fashion and were undetectable after 5 days post-infusion. Renal platinum levels decreased in the same manner as the plasma levels and revealed detectable plateau levels 5 days after single injection. Cisplatin was administer once a week for 3 consecutive weeks; serial plasma and renal platinum levels and BUN were measured 7 days after each injection. The results showed that there was no significant change in the levels of plasma platinum and BUN but that the renal platinum levels increased progressively (1.6 +/- 0.3, 3.1 +/- 0.4, 4.8 +/- 2.7 micrograms/g wet wt.). After another 6 successive weeks of cisplatin administration, 55% of mice died. The renal platinum levels and BUN of the survivors were highly increased. The renal tissue revealed histologically acute renal failure. However the renal concentration of platinum was decreased to a low level of 1.1 +/- 0.4 micrograms/g wet wt. 4 weeks after the third injection. These results suggested that cisplatin-induced nephrotoxicity could be ameliorated by adequate intervals of cisplatin administration.     

胸科手术中不同通气方式的患者血清中蛋白质组学的研究

目的应用同位素标记的绝对和相对定量（isobaric tags for relative and absolute quantitation，iTRAQ）技术筛选并鉴定胸科手术中分别采用单肺通气和双肺通气的患者血清中差异表达的蛋白质。方法收集胸科手术中采用单肺通气和双肺通气的患者血清，每组各10例，将每一组血清等量混合后应用多重免疫亲和层析柱（MARS）去除血清中的高丰度蛋白，样本经iTRAQ标记和液相色谱分离后，用质谱仪进行鉴定和相对定量分析。结果经质谱鉴定共获得189种蛋白质，其中差异表达的蛋白质有42种（上调或下调20％）。单肺通气组与双肺通气组比较，有33种蛋白质表达上调，9种表达下调。结论iTRAQ技术能够快速、有效地进行差异蛋白质组学的研究，能筛选出多种与单肺通气肺损伤相关的生物标记蛋白，为进一步研究单肺通气肺损伤发生的机制提供实验依据。     

HL-60细胞向单核系和粒系分化的比较蛋白质组学研究

背景与目的：已有研究发现NSC67657和全反式维甲酸可以诱导HL-60细胞分别向单核系和粒系分化。本研究比较分析不同诱导剂诱导HL-60细胞向单核系和粒系分化前后以及分化中的蛋白表达差异,发现与单核系和粒系分化有关的关键蛋白。方法：分别采用粒系分化诱导剂全反式维甲酸和单核系分化诱导剂NSC67657诱导HL-60细胞分化,MTT法检测细胞增殖情况：流式细胞技术分析细胞表面特异性分化抗原（CD11b／CD14）的表达,根据CD14表达情况计算细胞分化百分率;细胞化学染色对HL-60的两系分化进行验证。改良双向电泳分离技术对HL-60细胞全蛋白进行分离,PDQuest软件分析寻找差异蛋白点,基质辅助激光解吸-飞行时间质谱（MALDI-TOFMS）对蛋白点进行分析,RT-PCR和免疫印迹对差异蛋白ICAT进行验证。结果：全反式维甲酸和NSC67657均抑制HL-60细胞增殖,并分别诱导HL-60细胞向粒系和单核系分化。在2μmol／LATRA和10μmol／LNSC67657作用5d后．CD11b和CD14的表达均在90％以上,细胞化学染色支持细胞两系分化的结论。蛋白质组学分析表明,HL-60细胞分别向粒系和单核系分化后,有25个差异蛋白点的变化趋势在两系分化中是相同的,有10个差异蛋白点在单核系分化后表达有差异。有15个差异蛋白点在粒系分化后表达有差异：ICAT是其中差异蛋白之一,通过基因和蛋白水平验证．发现ICAT在NSC67657诱导HL-60细胞单核系分化过程中表达升高,而在粒系和非处理细胞中表达无显著性差异。结论：双向电泳／MOLDI-TOFMS对HL-60细胞分化前后细胞全蛋白进行分析．发现了一批与两系分化有关的蛋白分子．为关键蛋白的筛选及其功能研究提供了重要的启示。     

Direct amifostine effect on renal tubule cells in rats.

Clinical trials indicate that amifostine offers protection against cisplatin-induced nephrotoxicity. It is unclear whether a direct pharmacological t on renal tubular cells is involved. We investigated the effect of amifostine pretreatment on the tubular apparatus and evaluated its nephroprotective potential. A total of 32 rats were treated by i.p. administration of 0.9% saline solution (group 1), 5 mg/kg cisplatin (group 2), 25 mg/kg amifostine (group 3), and 25 mg/kg amifostine followed by 5 mg/kg cisplatin (group 4) after 30 min. We recorded elevation of N-acetyl-beta-D-glucosaminidase (NAG) in 24 h pooled urine as a specific marker for tubular lesions, renal leakage of magnesium as an unspecific nephrotoxicity marker, and survival over a 10-day observation period. A significant (P < 0.002) increase in urinary NAG after treatment was documented only in cisplatin-treated group 2 [day 2 (mean+/-SE), 93+/-2.1 units/gram creatinine; day 4, 70.6+/-16 units/gram creatinine; normalization at day 8]. Treatment with amifostine before cisplatin administration resulted in a slight urinary NAG leakage (day 2, 2.8+/-1.8 units/gram creatinine; day 4, 13.8+/-13 units/gram creatinine; normalization at day 6). No increase in urinary enzyme levels was seen in the other groups, and there were no significant differences in urinary magnesium between all groups. Four of eight rats in the cisplatin-treated group and one of eight rats in the amifostine plus cisplatin-treated group died.