The Effect of Lutein Pretreatment on Cisplatin-lnduced Hepatic Ultrastructure Damage in Rats

目的:观察叶黄素(LU)对顺铂(CP)损伤大鼠肝组织超微结构的影响.方法:将24只雌性SD大鼠随机分为生理盐水组(NS组)、顺铂化疗组(CP组)和LU干预组(LU+CP组),每组8只.NS组及CP组大鼠灌胃玉米油2mL/kg,LU+CP组大鼠灌胃20 g/L的LU油溶液2mL/kg.灌胃7 d后,CP组和LU+CP组腹腔注射1g/L的CP 5 mg/kg,NS组腹腔注射等容量生理盐水.注射CP后第5天剖取肝脏,在光镜、透射电镜下观察大鼠肝组织形态结构改变.结果:LU+CP组的CP所致的肝细胞质空泡化及肝门管区纤维化等改变较CP组减轻,同时LU+CP组CP引起的线粒体嵴结构断裂或消失、粗面内质网呈片层状及染色质边集于核膜下等超微结构改变也较CP组减轻.结论:预防性喂饲LU可对CP所致的大鼠肝脏病理及超微结构损伤产生一定的保护作用.     

苍术素对牙周炎大鼠牙周组织炎性损伤和牙槽骨丢失的影响及机制

目的 探讨苍术素对牙周炎大鼠牙周组织炎性损伤和牙槽骨丢失的影响及机制。方法 将144只SD大鼠分为对照组（灌胃且腹腔注射生理盐水）,模型组（灌胃且腹腔注射生理盐水）,苍术素低、中、高剂量组（分别腹腔注射6.665、13.33、26.66 mg/kg苍术素且灌胃生理盐水）,甲硝唑组（阳性对照组,灌胃0.05 g/kg甲硝唑且腹腔注射生理盐水）,AMD3100[基质细胞衍生因子1(SDF-1)/CXC型趋化因子受体4(CXCR4)通路抑制剂]组（灌胃1 mg/kg AMD3100且腹腔注射生理盐水）,苍术素高剂量+AMD3100组（腹腔注射26.66 mg/kg苍术素且灌胃1 mg/kg AMD3100）,每组18只。除对照组外,其余各组大鼠均采用牙龈内接种牙龈卟啉单胞菌法构建牙周炎模型。建模成功后开始给药,每天给药（或生理盐水）1次,持续4周。检测大鼠牙龈指数;检测大鼠血清中白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平;采用亚甲蓝染色、HE染色、抗酒石酸磷酸酶染色法分别检测牙槽骨吸收、牙周组织病理变化、破骨细胞数;检测大鼠骨保护素（OPG）、核因子κB受体活化因子配基（RA...     

川芎嗪对大鼠肝脏缺血再灌注损伤的保护作用

目的：研究川芎嗪对大鼠肝脏缺血再灌注损伤的保护作用及其机制。方法：SD大鼠随机分为5组：空白对照组、假手术组、缺血再灌注组、生理盐水组和川芎嗪组。其中空白对照组大鼠直接处死;假手术组开腹后60 min关闭腹腔;缺血再灌注组阻断70%肝血流60 min,再灌注4 h;生理盐水组予腹腔内注射生理盐水8 ml/kg,30 min后阻断70%肝血流60 min,再灌注4 h;川芎嗪组予腹腔内注射川芎嗪80 mg/kg,30 min后阻断70%肝血流60 min,再灌注4 h。速率法测血清丙氨酸氨基转移酶（alanine aminotransferase,ALT）和天冬氨酸氨基转移酶（aspartate aminotransferase,AST）活性,酶联免疫吸附法（ELISA）测血白介素-1（IL-1）、白介素-10（IL-10）和肿瘤坏死因子-α（TNF-α）水平。苏木素-伊红染色观察肝脏病理改变。结果：川芎嗪组血清ALT、AST、IL-1和TNF-α水平均比缺血再灌注组和生理盐水组明显降低（P〈0.05）,而IL-10则明显高于缺血再灌注组和生理盐水组（P〈0.05）。病理结果显示,川芎嗪组大鼠肝细胞损伤较缺血再灌注组和生理盐水组为轻。结论：川芎嗪对大鼠肝脏缺血再灌注损伤具有保护作用,其机制可能与抑制炎性细胞因子生成及促进抗炎细胞因子表达有关。     

银杏叶提取物与阿托伐他汀联合应用对大鼠CYP450蛋白水平的影响

目的观察银杏叶提取物与阿托伐他汀联合应用对大鼠CYP450蛋白水平的影响。方法将24只SD大鼠随机分为生理盐水(NS)组、阿托伐他汀(AV-T)组、银杏叶提取物(GBE)组、GBE联合AV-T组,每组6只。NS组用生理盐水1 m L/(kg·d)灌胃,AV-T组1 mg/(kg·d)AV-T灌胃,GBE组50 mg/(kg·d)GBE灌胃,GBE联合AV-T组GBE 50 mg/(kg·d)联合AV-T 1 mg/(kg·d)灌胃。6周后,取大鼠肝脏,制备肝微粒体,CO-还原差示光谱法检测肝微粒体CYP450酶含量;Western blot检测肝脏组织中CYP3A4和CYP2C9蛋白的表达。结果与NS组及AV-T组相比,GBE组、GBE+AV-T组CYP450酶含量明显升高(P<0.01)。与NS组及AV-T组相比,GBE组、GBE+AV-T组CYP3A4的表达显著降低(P<0.01,P<0.05);GBE组、GBE+AV-T组CYP2C9的表达显著上升(P均<0.01)。结论 GBE与AV-T联合应用后,使大鼠肝微粒体CYP450含量增高,且影响CYP3A4和CYP2C9的蛋白表达,由此可能会影响AV-T的疗效。     

黄芪甲苷对异丙肾上腺素诱导大鼠 心肌肥厚的保护作用研究

摘要：目的 探讨黄芪甲苷对异丙肾上腺素（ISO）诱导的大鼠心肌肥厚的保护作用机制。方法 健康SPF级SD 大鼠24只,随机分为4组,对照组（与ISO组等体积的生理盐水腹腔注射,之后与黄芪甲苷组等体积生理盐水灌胃）、 ISO组［ISO 3 mg/ （kg·d）腹腔注射,与黄芪甲苷等体积生理盐水灌胃］、黄芪甲苷组［与ISO等体积生理盐水腹腔注射, 黄芪甲苷溶液5 mg/ （kg·d）灌胃］、黄芪甲苷+ISO组［ISO 3 mg/ （kg·d）腹腔注射,黄芪甲苷溶液5 mg/ （kg·d）灌胃］,每 组6只,共处理14 d。处理结束后取大鼠左心室,计算左心室质量指数（左心室质量/体质量）。HE染色观察左心室心 肌肥厚情况,比较心肌横截面积的差异。以二氯荧光素（DCF）为探针检测心肌线粒体活性氧（ROS）生成速率; Western blot 法检测大鼠心肌NADPH氧化酶4（NOX4）和心房利钠肽（ANP）蛋白表达水平;RT-qPCR检测大鼠心肌 ANP在转录水平的表达情况。结果 与对照组相比,ISO组左心室质量指数明显升高,心肌横截面积扩大,心肌线粒 体ROS生成速率加快,NOX4蛋白、ANP mRNA及蛋白表达水平均明显升高（P < 0.05）。而ISO+黄芪甲苷组与ISO组 相比,上述指标均明显改善,主要表现为心肌横截面积缩小,ROS生成速率减慢,NOX4蛋白、ANP mRNA及蛋白表达 明显下降,差异均有统计学意义（P＜0.05）。结论 黄芪甲苷对ISO诱导的大鼠心肌肥厚具有确切的保护作用,且该 保护作用可能与黄芪甲苷降低氧化应激反应相关。     

促红素预防顺铂所致的大鼠急性肾功能衰竭的肾脏保护作用

目的观察促红细胞生成素（EPO）预防顺铂所致的急性肾衰竭（ARF）大鼠肾损伤的效果。方法正常对照组：腹腔注射生理盐水7ml/kg体重;ARF组：腹腔单次注射顺铂7mg/kg体重;促红素预防组：单次腹腔注射顺铂7mg/kg体重前0.5h皮下注射EPO5000Iu/kg体重。其中ARF组、促红素预防组各分为1d,3d,5d,7d,10d等5个观察亚组。观察各组大鼠尿量、肾功能和肾组织病理变化。结果与ARF组相比,EPO预防组血尿素氮、血肌酐浓度均明显降低,ATN评分下降（P〈0.05）。ARF组大鼠3d肾组织中出现明显的小管细胞凋亡,EPO预防组凋亡减轻;ARF组肾小管出现明显再生的时间晚于EPO预防组。结论预防性注射大剂量EPO可减轻顺铂诱导的大鼠急性肾功能衰竭肾组织病理改变,且促进肾小管再生。     

姜黄素保护刀豆蛋白A诱导的小鼠肝损伤作用的研究

目的：研究姜黄素（curcumin,Cur）对刀豆蛋白A（concanavalin A,Con A）诱导的小鼠肝损伤的保护作用及可能机制。方法：40只ICR小鼠被随机均分为正常对照组、模型组、Cur100 mg/kg组和200 mg/kg组。受试物组每天灌胃姜黄素液,模型组和正常对照组每天灌胃同体积生理盐水,连续10 d。末次给药后4 h,除正常对照组外均采用尾静脉注射Con A 20 mg/kg,8 h后检测被测试动物肝匀浆液的丙二醛（MDA）和超氧化物歧化酶（SOD）指标及血清ALT、AST指标,观察肝组织病理学改变。结果：与模型组相比,受试物组ALT、AST活力均显著降低,肝脏MDA水平降低,SOD活力提高,肝组织病理改变减轻。结论：姜黄素具有减轻肝损伤的作用,该作用可能通过减轻肝脏的氧化应激损伤来实现。     

扶正解毒颗粒对硫酸镍染毒大鼠镍代谢的影响

目的 探讨扶正解毒颗粒(FJK)对硫酸镍染毒大鼠镍代谢的影响.方法 选择健康成年SD大鼠32只,随机分为4组:生理盐水(NS)组,NiSO42.5mg/kg组,NiSO42.5mg/kg FJK 10g/kg处理组,NiSO42.5mg/kg 5g/kg处理组.NiSO4组:每天NiSO42.5mg/kg腹腔注射染毒,连续30d,于第10天生理盐水10ml/kg灌胃,连续21d.FJK处理组:染毒方法及剂量同NiSO4组,于第10天以FJK 10、5g/kg灌胃处理,1次/d,连续21d.对照组用生理盐水等容积腹腔注射和灌胃.于第9天和第30天分别收集各组血、尿、粪样,用原子吸收分光光度计检测其镍含量.结果 与硫酸镍组比较,FJK可使染镍大鼠血清中镍含量降低(P<0.01),尿液、粪便中镍含量升高(P<0.05);FJK处理前后比较,FJK处理后大鼠尿液和粪便中镍排出量均明显增加(P<0.05).结论 FJK可降低大鼠体内镍含量,并促使体内镍的排泄.     

原花青素对D-半乳糖复合三氯化铝诱导大鼠主动脉损伤的保护作用及机制

目的：探讨原花青素对D-半乳糖复合三氯化铝诱导大鼠主动脉损伤的保护作用及可能机制。方法： 采用D-半乳糖（D-gal）腹腔注射（ip）180mg/kg/d 联合三氯化铝（AlCl3）灌胃（ig）15mg/kg/d建立主动脉损伤大鼠模型,12周后将40只大鼠随机分为空白对照组（NS ip,NS ig）,主动脉损伤组（D-gal ip ＋ AlCl3 ig）,原花青素低、高剂量组（PC 20、40 mg/kg; D-gal ip＋AlCl3 ig）,维生素E组（VitE 10 mg/kg;D-gal ip ＋ AlCl3 ig）,每组8只。每日灌胃给药一次,连续8周。于末次给药后,尾袖法测量大鼠尾动脉血压;离体灌流法观察主动脉环对乙酰胆碱的舒张反应;HE染色观察主动脉病理变化;化学比色法测定血清总抗氧化能力、过氧化氢以及一氧化氮含量;免疫组化法观察主动脉内皮型一氧化氮合酶（eNOS）表达。结果：与模型组相比,随着原花青素剂量的增加,大鼠血压逐渐降低,主动脉内皮依赖性舒张功能逐渐增强,主动脉病理损伤得到不同程度的改善;血清中T-AOC 和NO含量逐渐增高,H2O2含量逐渐降低;主动脉eNOS蛋白表达逐渐增加。结论：原花青素可明显降低主动脉血压,增强主动脉环内皮依赖性舒张反应,减轻主动脉病理损伤,增高血清NO水平,上调主动脉eNOS蛋白的表达,对D-半乳糖复合三氯化铝诱导的大鼠主动脉损伤有一定保护作用。     

褪黑素减轻丙烯酰胺对大鼠小脑的氧化损伤作用

目的探讨褪黑素(Melatonin,MT)是否能减轻丙烯酰胺(ACR)导致的大鼠小脑的氧化损伤。方法 52只SD雄性大鼠按体重随机分为4个组,每组13只,分别为对照组、ACR组、MT组、MT+ACR联合组,均单笼饲养。对照组灌胃溶剂生理盐水,ACR组灌胃40 mg/kg ACR溶液,MT组腹腔注射5 mg/kg MT,MT+ACR联合组灌胃40 mg/kgACR溶液同时腹腔注射5 mg/kg MT,连续12 d。染毒结束后,断头处死大鼠,在冰盘上分离小脑,对小脑进行苏木素-伊红(HE)染色、氧化损伤检测和DNA损伤检测。结果 ACR组出现浦肯野细胞核固缩等异常改变,丙二醛(MDA)含量明显升高(P<0.05),T-SOD活性和GSH含量明显下降(P<0.05,P<0.01),彗星试验中尾长,尾部DNA百分含量及Olive尾距均显著增加,差异均有统计学意义(P<0.05或P<0.01)。MT+ACR组小脑结构正常,与ACR组相比,MT+ACR组MDA含量、彗星试验尾长、尾部DNA百分含量、Olive尾距均明显下降,T-SOD活性和GSH含量明显升高,差异均有统计学意义(P<0.05或P<0.01)。结论 ACR可以引起大鼠小脑结构改变、氧化损伤和DNA损伤,MT可以减轻ACR对小脑的结构损伤和氧化损伤。     

Effect of curcumin nanoparticles on the cisplatin-induced neurotoxicity in rat

The present study is conducted to evaluate the neuroprotective effect of curcumin nanoparticles (CUR NP) against the neurotoxicity induced by cisplatin (CP) in rat. Rats were divided into control group that received saline solution, CP-treated rats that received a single i.p. injection of CP (12?mg/kg body wt), and CP-treated rats that received a single i.p injection of CP (12?mg/kg body wt) followed by a daily oral administration of CUR NP (50?mg/kg body wt) for 14 days. At the end of the experiment, the motor activity of rats was evaluated by open field test. The neurochemical and histopathological changes were investigated in the cerebral cortex. A significant decrease in motor activity was observed in CP-treated rats. This was associated with a significant increase in the cortical levels of lipid peroxidation, nitric oxide, tumor necrosis factor-α, caspase-3, and acetylcholinesterase activity. However, CP induced a significant decrease in reduced glutathione levels and Na⁺, K⁺-ATPase activity. In rats treated with CP and CUR NP, no significant changes were recorded in the parameters of the open field test as compared to control. In addition, treatment with CUR NP prevented all the neurochemical changes induced by CP except the increased value of nitric oxide. CUR NP also reduced the histopathological changes induced by CP. It is clear from the present data that CUR NP could ameliorate the neurotoxic effect induced by cisplatin.     

隐丹参酮对脂多糖诱导肝硬化大鼠肝性脑病的改善作用研究

目的研究隐丹参酮对脂多糖诱导肝硬化大鼠肝性脑病的改善作用,并探讨其作用机制。方法 SD大鼠随机分为对照组、模型组以及隐丹参酮5、15、45 mg/kg组,每组15只。模型组和隐丹参酮组背部sc 40%CCl4橄榄油溶液0.3m L/100 g(首次加倍),制备大鼠肝硬化模型;对照组背部sc等体积橄榄油溶液,2次/周。在实验第10周结束时开始给药。隐丹参酮组分别ig隐丹参酮5、15、45 mg/kg,对照组和模型组ig等体积生理盐水,1次/d,共2周。在第12周结束时所有大鼠禁食过夜,模型组和隐丹参酮组大鼠iv脂多糖2 mg/kg诱导肝性脑病,对照组iv等剂量无菌生理盐水。观察各组大鼠的肝脏组织病理学形态;采用血生化法检测大鼠的肝功能指标丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平和血氨水平,采用酶联免疫吸附(ELISA)法测定血浆中内毒素水平;考察大鼠肝性脑病分期和神经行为;观察神经细胞5-溴-2′-脱氧尿嘧啶(Brd U)染色情况,计算Brd U阳性率;Western blotting试验测定脑源性神经营养因子(BDNF)的表达。结果隐丹参酮组大鼠肝脏组织病理学形态发生明显改善,血清中ALT、AST水平较模型组明显降低(P0.05、0.01),并呈现一定的剂量相关性。隐丹参酮组大鼠的血氨、内毒素水平均比模型组显著降低(P0.05、0.01),并具有一定的剂量相关性。隐丹参酮组大鼠的肝性脑病分期评分明显优于模型组(P0.01),并且反射评分也得到明显改善,在隐丹参酮15、45 mg/kg组中尤为明显。隐丹参酮组神经细胞再生能力逐渐增强,在隐丹参酮45 mg/kg组中可以检测到明显的Brd U阳性细胞。隐丹参酮15、45 mg/kg组大鼠的Brd U阳性率均比模型组显著升高(P0.05、0.01),并具有一定的剂量相关性。随着隐丹参酮剂量的增加,BNDF的表达与模型组比较出现明显升高。结论隐丹参酮对脂多糖诱导肝硬化大鼠肝性脑病具有明显的改善作用,其作用机制与隐丹参酮对肝性脑病大鼠肝功能的改善,血清中血氨、内毒素水平的降低,肝性脑病分期的改善,神经行为能力的提高,BDNF表达的增强以及对神经细胞再生的促进作用有关。     

马来酸曲美布汀对慢性胰腺炎大鼠胃肠运动功能的影响

目的:研究慢性胰腺炎(CP)大鼠胃肠运动功能的变化及马来酸曲美布汀对CP的治疗效果。方法:健康Wistar大鼠30只,随机分为对照组、慢性胰腺炎组(模型组)和马来酸曲美布汀组(治疗组),每组10只。治疗组给予马来酸曲美布汀溶液灌胃,剂量为0.2mL/kg,1次/d;模型组及对照组灌注等量的生理盐水,3组均灌注2周。采用酶联免疫吸附(ELISA)法测定血清胆囊收缩素(CCK)水平,采用硝酸还原酶法测定血清NO水平;检测各组小肠运动系数、胃窦及小肠环行平滑肌肌条收缩能力、环行平滑肌细胞收缩反应;测定胃肠肌层诱导型一氧化氮合酶(iNOS)mRNA的表达量。结果:模型组小肠运动系数、胃窦和小肠环行平滑肌肌条的收缩力、平滑肌细胞收缩反应均低于对照组和治疗组,差异有统计学意义(均P<0.01);模型组CCK、NO及iNOSmRNA水平均高于对照组和治疗组,差异有统计学意义(P<0.01)。结论:马来酸曲美布汀可有效改善CP所致的胃肠动力障碍。     

MCP-1参与缬沙坦对阿霉素心脏毒性的预保护作用

目的　探讨阿霉素诱导SD大鼠心肌损伤模型中单核细胞趋化蛋白-1（MCP-1）蛋白表达及其潜在的干预机制。方法　选择8周龄雄性SPF级SD大鼠30只,按照随机数字表法分为3组：对照组（Con组,生理盐水灌胃＋腹腔注射）、阿霉素组（Dox组,1.25 mL/kg阿霉素腹腔注射+2 mL/kg生理盐水灌胃）及缬沙坦+阿霉素组（Val+Dox组,1.25 mL/kg阿霉素腹腔注射+2 mL/kg缬沙坦灌胃）各10只,连续干预6周。10周时超声心动图检测心功能变化,留取大鼠心肌组织,电镜观察心肌超微结构变化,采用蛋白芯片技术检测各组血清MCP-1、调节激活正常T细胞表达和分泌因子（RANTES）及次级淋巴组织趋化因子（6Ckine）蛋白含量,采用Western blot检测各组心肌组织MCP-1蛋白表达。结果　超声结果显示,与Con组相比,Dox组和Val+Dox组左心室射血分数（LVEF）、左心室短轴缩短率（LVFS）明显降低,左心室收缩末期内径（LVESD）、左心室舒张末期内径（LVEDD）明显升高（P＜0.05）。与Dox组相比,Val+Dox组LVEF、LVFS明显升高,LVESD、LVEDD明显降低（P＜0.05）。电镜下可见Con组心肌细胞结构清晰;Dox组心肌结构模糊,心肌溶解,可见自噬小体;Val+Dox组心肌结构模糊不清,线粒体体积增大、大小不等,但结构完整。与Con组相比,Dox组血清MCP-1、RANTES、6Ckine蛋白分别上调1.87倍、1.40倍和1.26倍（P＜0.05）。Western blot结果显示,Dox组与Con组相比,心肌组织MCP-1蛋白表达显著升高（P＜0.05）;Val+Dox组与Dox组相比,心肌组织MCP-1蛋白表达显著降低（P＜0.05）。结论　MCP-1蛋白可能参与阿霉素诱导的心肌损伤,缬沙坦可能通过下调MCP-1蛋白表达减轻心肌损伤。     

N-乙酰半胱氨酸对体外循环致大鼠脑损伤的保护作用

目的:探讨N-乙酰半胱氨酸(NAC)对体外循环(CPB)致大鼠脑损伤的保护作用.方法:将24只成年雄性SD大鼠随机分为假手术组(S组)、CPB组(C组)、CPB+NAC组(N组),每组8只.N组在CPB预充液中加入NAC 100mg/kg,然后以20 mg/(kg·h)速度输注直到停转流,C组输注等量生理盐水.停CPB后2h,测定血浆神经元特异性烯醇化酶(NSE)、S-100β蛋白、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平,检测脑组织丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-px)含量,透射电镜下观察海马区神经元细胞超微结构的变化.结果:与S组比较,C组血浆NSE,C组和N组血浆S-100β蛋白、TNF-α和IL-6水平及脑组织MDA、GSH-px含量均发生一定程度的改变;且N组血浆NSE、S-100β蛋白、TNF-α和IL-6水平,脑组织MDA和GSH-px含量均显著优于C组.与S组比较,C组和N组海马区神经元细胞超微结构均有一定程度的病理学改变,且N组的损伤程度较C组明显减轻.结论:NAC可减轻CPB致大鼠脑损伤,其机制可能与抗氧化、抗炎作用有关.     

银杏叶片长期给药后对大鼠灌服氯沙坦的药代动力学影响

目的:研究银杏叶提取物(GBE)制剂银杏叶片长期给药后对大鼠灌服氯沙坦(Los)的药代动力学影响.方法:SD大鼠随机分为Los单用组,GBE+ Los联合用药组.试验第1天起,联合用药组大鼠灌胃给予GBE 100 mg/kg,共14 d.单用组大鼠灌胃给予等量纯净水.第15天,单用药组大鼠灌胃给予Los 10 mg/kg,GBE+Los联合给药组大鼠同时灌胃给予GBE 100 mg/kg和Los 10 mg/kg.于Los给药后0.5、1、2、3、4、6、8、10、12、24 h从大鼠眼眦静脉丛取血.HPLC法测定血浆中Los及其活性代谢产物EXP3174的浓度,计算其主要药代动力学参数,并进行统计学分析.结果:合用GBE后,Los的各药代动力学参数差异无统计学意义.EXP3174的tmax显著缩短(P＜0.05),Cmax、AUC0-8和AUC0-∞显著增加(P＜0.01),CL显著降低(P＜0.05),t1/2、MRT变化无统计学差异.结论:GBE能够影响EXP3174的体内代谢,但对Los的药代动力学过程影响没有统计学意义.     

Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer. High doses of cisplatin have also been known to produce hepatotoxicity, and several studies suggest that supplemental antioxidants can reduce cisplatin-induced hepatotoxicity. The present study was designed to determine the effects on the liver and heart oxidant/antioxidant system and the possible protective effects of ellagic acid on liver and heart toxicity induced by cisplatin. The control group received 0.9% saline; animals in the ellagic acid group received only ellagic acid (10 mg/kg); animals in the cisplatin group received only cisplatin (7 mg/kg); animals in cisplatin + ellagic acid group received ellagic acid for 10 days after cisplatin. The rats were killed at the end of the treatment period. Malondialdehyde (MDA) and glutathione (GSH) levels, glutathione-peroxidase (GSH-Px) and catalase (CAT) activities were determined in liver and heart tissue. While administration of cisplatin increased the MDA levels in liver and heart tissues, it decreased the GSH, GSH-Px and CAT in these samples when compared to the control group. The administration of ellagic acid to cisplatin-treated rats decreased the MDA levels, and increased GSH, GSH-Px and CAT in these samples. Cisplatin caused marked damages in the histopathological status of liver and heart tissues. These damages were ameliorated by ellagic acid administration. In conclusion, ellagic acid may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters.     

The effects of desferrioxamine on cisplatin-induced lipid peroxidation and the activities of antioxidant enzymes in rat kidneys

Cisplatin-induced nephrotoxicity is associated with an increase in lipid peroxidation and oxygen free radicals in rat kidneys. In this study, the effects of desferrioxamine were compared to vitamin C and E on cisplatin-induced lipid peroxidation and antioxidant enzyme activities in rat kidneys. Rats were divided into five groups, with 15 Wistar rats in each group. In the control group, rats received 1 mL/100 g isotonic saline solution intraperitoneally (i.p.). In Group II, 10 mg/kg cisplatin i.p. was injected to rats. Thirty minutes before the same dosage of cisplatin administration, 100 mg/kg i.p. vitamin C or E was given to rats in groups III and IV, respectively. Rats in Group V received 250 mg/kg desferrioxamine i.p., before the same dose of cisplatin administration. All rats were killed by cervical dislocation after 72 hours. The kidneys were immediately removed and washed in cold saline. Spectrophotometric method was used for all analyses. While catalase, glutathione reductase (GR), and superoxide dismutase (SOD) levels were found to be significantly decreased (P < 0.001), malondialdehyde (MDA) (P < 0.05) and hydrogen peroxide (H2O2) (P < 0.001) levels were significantly increased in the cisplatin group when compared to the controls. MDA levels were decreased by desferrioxamine (P < 0.005) as well as vitamin C and E (P < 0.05 and P < 0.001, respectively). These three compounds induced a significant increase in SOD levels (P < 0.05), but only in the vitamin C group, were SOD levels not significantly different than the levels of the controls (P > 0.05). In the desferrioxamine (P < 0.05), vitamin C and E groups (P < 0.001 for both), the cisplatin elevated H2O2 levels were decreased. None of these drugs had any effect on GR and catalase levels (P > 0.05). Desferrioxamine is useful to prevent cisplatin-induced lipid peroxidation, however, vitamin C and E are more effective on antioxidant enzymes than desferrioxamine.     

The protective effects of acetylsalicylic acid on free radical production in cisplatin induced nephrotoxicity: an experimental rat model

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.     

Effects of lycopene against cisplatin-induced nephrotoxicity and oxidative stress in rats

The aim of this study was to investigate the effects of lycopene on cisplatin-induced nephrotoxicity and oxidative stress in rats. Adult male Sprague-Dawley rats were randomly divided into four groups. The control group (group 1) received physiological saline; animals in group 2 received only cisplatin; a 10 days of lycopene pre-treatment was applied to the animals in group 3 before administration of cisplatin; a 5 days of lycopene treatment was performed following administration of cisplatin for the animals in group 4. Cisplatin (7 mg/kg) was intraperitoneally injected as a single dose and lycopene (4 mg/kg) was administered by gavage in corn oil. Biochemical and histopathological methods were utilised for evaluation of the nephrotoxicity. The concentrations of creatinine, urea, Na+ and K+ in plasma and levels of malondialdehyde and reduced glutathione as well as glutathione peroxidase and catalase activities were determined in kidney tissue. Administration of cisplatin to rats induced a marked renal failure, characterized with a significant increase in plasma creatinine and urea concentrations. Na+ and K+ levels of rats received cisplatin alone were not significantly different compared to control group, but they had higher kidney malondialdehyde, and lower reduce glutathione concentrations, glutathione peroxidase and catalase activities. Lycopene administration produced amelioration in biochemical indices of nephrotoxicity in both plasma and kidney tissues when compared to group 2; pre-treatment with lycopene being more effective. Results from this study indicate that the novel natural antioxidant lycopene might have protective effect against cisplatin-induced nephrotoxicity and oxidative stress in rat.