褪黑素联合顺铂对A549细胞凋亡相关基因的影响

观察褪黑素以及褪黑素联合顺铂是否可以抑制A549细胞增殖并促进细胞凋亡,探讨ERK1/2MAPK信号通路在这一过程中的作用,为肺腺癌的研究提供实验依据。用不同浓度的褪黑素、不同浓度的顺铂、褪黑素联合顺铂刺激体外培养的肺腺癌细胞系A549细胞,MTT法检测各组细胞的活性,运用Real-time RT-PCR检测凋亡相关基因Bcl-2、Bax、p53的表达水平,Western-blot检测ERK1/2MAPK的活性变化。结果:1)单纯使用褪黑素和顺铂均可抑制A549细胞增殖,褪黑素联合顺铂时,抑制作用更加显著,一定浓度的褪黑素可降低顺铂的使用浓度;2)未经处理的A549细胞Bcl-2/Bax很高,p53基因表达较低,经褪黑素以及褪黑素联合顺铂刺激后A549细胞中Bcl-2/Bax明显下降,p53基因表达明显升高,并有浓度依赖;3)经褪黑素和顺铂刺激后A549细胞中磷酸化ERK1/2MAPK水平明显降低。褪黑素联合顺铂可抑制A549细胞增殖并且诱导凋亡相关基因表达,褪黑素和顺铂对A549细胞的抑制作用可能与ERK1/2MAPK信号通路有关。     

康莱特联合顺铂对宫颈癌SiHa细胞增殖和凋亡的影响

目的:通过康莱特联合顺铂对宫颈癌SiHa细胞增殖和凋亡的影响,探讨其作用机制。方法:体外培养宫颈癌Siha细胞,分别将康莱特(浓度为1,2,4,6,8 mg/mL),顺铂(浓度梯度为1.5,3,6,9,12μg/mL),单独作用于宫颈癌SiHa细胞,加药24h、48h用噻唑蓝(MTT法)检测细胞增殖情况。用流式细胞术检测康莱特组和顺铂组细胞24h凋亡率,选取合适的药物浓度(康莱特6 mg/mL,顺铂3μg/mL),进行联合用药,加药24h、48h用MTT法检测细胞增殖情况,用流式细胞术检测24h细胞凋亡率。结果:①MTT法显示加药后两组的24h、48h,宫颈癌SiHa细胞的抑制率均高于对照组(P0.05),并且在一定程度上呈浓度和时间依赖性。②联合用药时,细胞的抑制率和凋亡率要显著高于单独用药(P0.01)。结论:康莱特、顺铂单独或联合作用均能抑制SiHa细胞的增殖,促进其凋亡,且康莱特联合顺铂的作用要显著高于单独用药,康莱特与化疗药物联合使用可提高肿瘤细胞对化疗药物的敏感性。     

重组骆驼蓬脂转移蛋白与顺铂联合抑制黑色素瘤B16细胞增殖效应的研究

旨在探讨重组骆驼蓬脂转移蛋白(Recombinant Peganum harmala lipid transfer protein,r Ph LTP)与顺铂(DDP)联用对鼠黑色素瘤B16细胞增殖抑制和凋亡诱导作用。MTT法检测r Ph LTP、顺铂单独及联用后对鼠黑色素瘤B16细胞增殖的影响;流式细胞术检测细胞凋亡,活性氧(Reactive oxygen species,ROS)和线粒体膜电位(Δψm)的变化情况。结果显示,r Ph LTP和DDP联用后细胞生长抑制率和凋亡率显著高于DDP单独处理组(P0.01);而且胞内ROS升高的水平均高于单独处理组(P0.01),胞内Δψm水平均低于单独处理组,但无显著性差异。r Ph LTP可增强顺铂对B16细胞的生长抑制并促进细胞凋亡,与顺铂具有协同作用。     

华蟾素联合顺铂对人骨肉瘤U2OS细胞增殖和凋亡的影响

目的:研究华蟾素联合顺铂对人骨肉瘤U2OS细胞增殖和凋亡的影响,并探寻联合治疗增敏的可能分子机制。方法:采用不同浓度的华蟾素、顺铂单药和华蟾素联合顺铂处理人骨肉瘤U2OS细胞1-3天,通过CCK-8法检测其对U2OS细胞生长的抑制作用;平板克隆实验检测其对U2OS细胞集落形成能力的影响;流式细胞仪检测其对U2OS细胞凋亡的影响;RT-PCR及Western blotting检测Bax、Bcl-2、caspase-3、caspase-9等凋亡相关分子mRNA及蛋白水平的表达。结果:单用华蟾素或顺铂均可以浓度和时间依赖的方式抑制骨肉瘤U2OS细胞的增殖并诱导其凋亡,两药联合应用具有协同效应,并可以上调促凋亡基因Bax下调抑制凋亡基因Bcl-2的表达;联合用药组凋亡相关蛋白caspase-3、caspase-9的表达较单药组明显增加。结论:华蟾素联合顺铂与单一用药相比能够显著抑制人骨肉瘤细胞U2OS细胞的增殖,促进其凋亡,两药联合应用对骨肉瘤细胞的杀伤效应具有一定的协同效应,其机制可能与激活凋亡通路有关。     

医学生科研创新能力培养“3+X”模式的探索与实践

针对长期以来培养医学生的科研创新能力主要依靠零散的课外科研活动、受众面窄、没有系统性课程教学及其相关制度保障、致使对医学生科研创新能力培养明显乏力低效这一共性瓶颈教学问题,自2002年起,汕头大学医学院生物化学与分子生物学教学团队,在“科教相辅相佐”、“以学生为中心”、“以问题为导向”等先进教育理念指导下,倚重汕头大学医学院“医者之心”系列课程与书院育人文化之特色,发挥汕头大学的生物学、基础医学和临床医学一级学科均拥有本/硕/博/博后完整人才培养体系之优势,联合其他相关专业教学团队,在建立充分体现医学生科研创新能力培养内涵,覆盖医学本科5年全过程的核心课程体系的基础之上,历经20载的不懈努力,补充修善,成功构建了“3+X”模式,着力培养医学生的科研创新能力。所谓“3”意指对医学生的“全人培养”、“全程培养”和“全方位培养”。所谓“X”意指针对“3+X”模式运行效能的若干个验证性维度,主要包括组织医学生参加各种形式的全国大学生创新实验研究大赛、国际大学生学术研讨会,由医学本科生作为第一作者撰写发表学术论文等。培养医学生科研创新能力的成效十分显著,为有效解决上述共性瓶颈教学问题提供了一个有重要借鉴价值的范例。     

重组骆驼蓬脂转移蛋白与顺铂联合抑制黑色素瘤B16细胞增殖效应的研究北大核心CSCD

旨在探讨重组骆驼蓬脂转移蛋白(Recombinant Peganum harmala lipid transfer protein,r Ph LTP)与顺铂(DDP)联用对鼠黑色素瘤B16细胞增殖抑制和凋亡诱导作用。MTT法检测r Ph LTP、顺铂单独及联用后对鼠黑色素瘤B16细胞增殖的影响;流式细胞术检测细胞凋亡,活性氧(Reactive oxygen species,ROS)和线粒体膜电位(Δψm)的变化情况。结果显示,r Ph LTP和DDP联用后细胞生长抑制率和凋亡率显著高于DDP单独处理组(P<0.01);而且胞内ROS升高的水平均高于单独处理组(P<0.01),胞内Δψm水平均低于单独处理组,但无显著性差异。r Ph LTP可增强顺铂对B16细胞的生长抑制并促进细胞凋亡,与顺铂具有协同作用。     

新合成黄腐酚类似物联合顺铂对宫颈癌细胞化疗增敏作用的研究

摘要 目的：探讨新合成黄腐酚类似物联合顺铂对宫颈癌Hela细胞化疗敏感性的影响及其机制。方法：以不同浓度（5、7.5、15、20 μmol/L）黄腐酚类似物处理宫颈癌Hela细胞和正常MRC-5细胞48 h后,MTT实验检测细胞增殖活力并计算出黄腐酚类似物对2种细胞的半数抑制浓度(IC₅₀);采用MTT实验进一步观察IC₅₀最低的黄腐酚类似物联合顺铂对Hela和MRC-5细胞增殖活力的影响,采用流式细胞仪检测Hela细胞周期和凋亡情况,Western blot法检测Hela细胞中凋亡相关蛋白表达变化。结果：黄腐酚类似物a8、a13、b11和b12对宫颈癌Hela细胞增殖均有一定的抑制作用,且a13的IC₅₀值最小;另外,这4种浓度的黄腐酚类似物对正常MRC-5细胞有轻微的抑制作用,且a13的IC50值最大。与对照组比较,顺铂组、a13组、顺铂+a13组中正常MRC-5细胞存活率差异均无统计学意义（P<0.05）,但顺铂组、a13组和顺铂+a13组中宫颈癌Hela细胞存活率、G2/M期细胞百分比和B淋巴细胞瘤-2基因（Bcl-2）蛋白表达水平均明显降低,而G0/G1期细胞百分比、细胞凋亡率和细胞中细胞色素C（Cyt-c）、Bcl-2关联X蛋白（Bax）、活化的半胱氨酸天冬氨酸蛋白酶3（Cleaved Caspase-3）、活化的半胱氨酸天冬氨酸蛋白酶9（Cleaved Caspase-9）蛋白表达水平均明显升高,且顺铂+a13组中上述指标变化幅度明显大于顺铂组、a13组（P<0.05）。结论：黄腐酚类似物与顺铂联合可协同抑制宫颈癌Hela细胞增殖,表现良好的化疗增敏效果,其作用机制可能与阻滞细胞周期进程和调控凋亡相关蛋白表达促进细胞凋亡有关。     

Genistein增加顺铂诱导的SKOV-3细胞的凋亡与活性氧的关系

目的:探讨Genistein增加顺铂诱导的耐药卵巢癌细胞SKOV-3凋亡的可能作用机制.方法:倒置相差显微镜下观察药物处理后细胞形态学的变化;MTT比色法检测不同药物处理后对SKOV-3细胞增殖的影响;流式细胞仪检测药物处理后细胞的凋亡情况;流式细胞仪和荧光显微镜检测细胞内活性氧(ROS)的水平.结果:10ug/ml的Genistein和2.5ug/ml的顺铂联用24h后,引起了细胞内ROS的增加,细胞的凋亡率也显著增高,与单用顺铂组相比差异有显著性(P＜0.05);用NAC预处理细胞2h后,有效抑制了ROS的产生,并增加了细胞的活性,降低了细胞的凋亡率,与未加NAC组相比差异有显著性(P＜0.05).结论:Genistein增加顺铂诱导的耐药卵巢癌细胞SKOV一3的凋亡与细胞内ROS水平的升高有关,这可能是Genistein增加顺铂诱导的耐药卵巢癌细胞SKOV-3凋亡的作用机制之一.     

巨噬细胞:一种理想的细胞骨架观察教学材料

细胞骨架是细胞的重要结构之一,也是《细胞生物学实验》教学的重要内容。然而,在目前的教学实践中,缺乏较为理想的细胞骨架观察材料。基于对巨噬细胞易黏附、便于操作特性的了解,该研究以小鼠腹腔巨噬细胞为材料,进行了细胞骨架显示的实验探索。结果表明,无论用曲通X-100处理细胞后再用考马斯亮蓝染色还是先对细胞进行固定、透膜后再用免疫荧光法染色,均可观察到清晰的细胞骨架结构。说明巨噬细胞是一种理想的细胞骨架观察教学材料。     

姜黄素联合顺铂对人骨肉瘤细胞增殖和凋亡的影响

目的:观察姜黄素联合顺铂对人骨肉瘤细胞MG-63增殖和凋亡的影响。方法:采用不同浓度的姜黄素、顺铂和姜黄素联合顺铂处理人骨肉瘤细胞MG-63不同时间,通过MTT法检测其对MG-63细胞生长的抑制作用;平板克隆实验检测其对MG-63细胞克隆形成能力的影响;流式细胞仪检测其对MG-63细胞凋亡的影响。结果:单用姜黄素或顺铂均可以时间和浓度依赖性方式抑制骨肉瘤细胞MG-63的增殖。与空白对照组相比,单用10μmol/L姜黄素和2、4μmol/L顺铂可抑制MG-63细胞的增殖,降低其克隆形成率并提高细胞凋亡率(P<0.05);而与姜黄素和顺铂单用处理相比,10μmol/L姜黄素分别与2、4μmol/L顺铂联合应用,可更显著抑制MG-63细胞的增殖,降低其克隆形成率并提高细胞凋亡率(P<0.01)。结论:姜黄素联合顺铂与单药相比能够显著抑制人骨肉瘤细胞MG-63细胞的增值,促进其凋亡,两药对骨肉瘤细胞的杀伤效应具有一定的协同性。     

Cav1.2在顺铂诱导C57BL/6J小鼠耳蜗螺旋神经元凋亡中的作用*

目的: 探究顺铂(CDDP)诱导C57BL/6J小鼠耳蜗螺旋神经元(SGNs)凋亡过程中Cav1.2的作用及其可能的机制。方法: 动物实验:选取8周龄雄性C57BL/6J小鼠分为以下两组(10只/组):生理盐水组(Control组)和顺铂给药组(Cisplatin组)。Control组每天腹腔注射生理盐水,Cisplatin组每周期前4 d以3 mg/kg的剂量进行顺铂腹腔注射,后10 d每日注射生理盐水,重复三个周期。给药结束后,听性脑干反应(ABR) 检测小鼠听力阈值变化; 小鼠内眦采血,并断颈取耳蜗,超氧化物歧化酶(SOD)以及丙二醛(MDA)试剂盒检测血清及耳蜗组织的SOD活性和MDA含量;免疫印迹法(Western blot)检测耳蜗组织相关凋亡蛋白表达;苏木精-伊红HE染色观察小鼠耳蜗螺旋神经节形态学变化; TUNEL 染色观察小鼠耳蜗SGNs凋亡情况;免疫荧光观察耳蜗SGNs上Cav1.2的分布和表达。细胞实验:原代培养SGNs,根据CCK8选择顺铂5 μmol/L干预12 h并随机分为:对照组(Control)、溶剂组(DMSO)、Cav1.2阻断剂组(N)、顺铂组(Cisplatin)、顺铂与Cav1.2阻断剂共同孵育组(Cisplatin+N)。Western blot检测Cav1.2蛋白表达;Hoechst33342染色观察各组SGNs凋亡情况,流式细胞术检测各组SGNs凋亡率,Western blot检测相关凋亡蛋白的表达,CA²⁺探针检测细胞内钙离子浓度变化,线粒体膜电位检测试剂盒(JC-1)检测膜电位变化,线粒体超氧化物指示剂(MitoSOX^TM-red)检测线粒体释放ROS情况。结果: 动物实验:与Control组相比,Cisplatin组小鼠听力阈值升高(P<0.01), 血清及耳蜗组织MDA含量、耳蜗组织凋亡蛋白 Cleaved-caspase-3、Bax 蛋白水平和TUNEL阳性率、Cav1.2蛋白表达水平等均明显升高(P<0.05, P<0.01);血清及耳蜗组织SOD活性、耳蜗组织抗凋亡蛋白 Bcl-2 蛋白水平和SGCs密度均明显降低(P<0.05,P<0.01)。细胞实验:与Control组相比,Cisplatin组的Cav1.2表达、细胞凋亡率、Cleaved-caspase-3、Bax蛋白水平、细胞内钙离子浓度以及ROS释放均明显增加(P<0.05,P<0.01);而细胞的Bcl-2蛋白水平和线粒体膜电位则明显降低(P<0.01);Cav1.2阻断剂可部分逆转上述改变(P<0.05)。 结论: 顺铂可能通过上调Cav1.2促进钙内流,进而使线粒体ROS增多,引起SGNs氧化应激损伤从而诱导线粒体途径的细胞凋亡。     

Protective Effects of Acetyl-<Emphasis Type="SmallCaps">l</Emphasis>-Carnitine on Cisplatin Cytotoxicity and Oxidative Stress in Neuroblastoma

The most widely used platinum-derived drug is cisplatin in neuroblastoma (NB) chemotherapy, which is severely neurotoxic. Acetyl-l-Carnitine (ALC) is a natural occurring compound with a neuroprotective activity in several experimental paradigms. The aim of this study was to determine the effects of ALC on cisplatin induced cytotoxicity and oxidative stress in NB cells. SH-SY5Y (N-Myc negative) and KELLY (N-Myc positive) human NB cell lines were used. Cisplatin induced apoptosis was assessed by using a Cell Death Detection ELISA^PLUS kit. Lipid peroxidation levels were determined by HPLC analysis. Glutathione levels were determined spectrophotometrically. ALC was used prophylactic or after cisplatin application. The level of cisplatin doses were determined in both type of NB cells at which 50% cell death occurred along with synchronized apoptosis induced. Prophylactic 10 and 50 μmol of ALC concentrations were decreased cisplatin induced lipid peroxidation compared to controls that normally exhibited apoptosis especially in SH-SY5Y cells. Cisplatin caused oxidative stress through decreasing glutathione levels in both cell types. ALC were effectively inhibited the increase in cisplatin induced oxidized glutathione and lipid peroxidation formation in NB cells. We suggested that prophylactic ALC would be a useful agent for cisplatin induced toxicity in NB cells.     

Loss of drug-induced activation of the CD95 apoptotic pathway in a cisplatin-resistant testicular germ cell tumor cell line

Testicular germ cell tumors (TGCTs) are unusually sensitive to cisplatin. In the present study the role of the CD95 death pathway in cisplatin sensitivity of TGCT cells was studied in Tera and its in vitro acquired cisplatin-resistant subclone Tera-CP. Cisplatin induced an increase in CD95 membrane expression, which preceded the onset of apoptosis. Cisplatin-induced apoptosis was efficiently blocked by caspase-8 inhibitor zIETD-fmk in Tera cells, but only partially in Tera-CP cells. In addition, cisplatin induced FADD and caspase-8 recruitment to the CD95 receptor in Tera cells, which was not noticed in Tera-CP cells. Moreover, overexpression of vFLIP reduced apoptosis induction by cisplatin in Tera cells. CD95L-blocking experiments revealed the involvement of CD95/CD95L interactions in cisplatin-induced apoptosis of Tera cells as well as cisplatin-sensitive 833KE TGCT cells. Tera and 833KE cells, treated with low doses of cisplatin, were sensitive for an apoptosis-inducing anti-CD95 antibody. In contrast, CD95L blocking had no effect on cisplatin-induced apoptosis in Tera-CP or Scha, an intrinsic resistant TGCT cell line, nor did anti-CD95 antibody induce additional apoptosis in cisplatin-treated Tera-CP or Scha cells. Taken together, these results show that (1) cisplatin sensitivity of TGCT cells is dependent on the activation of the CD95 death pathway and (2) loss of cisplatin-induced activation of this CD95 signaling pathway may result in resistance to cisplatin.     

Requirement for ERK activation in cisplatin-induced apoptosis

Cisplatin activates multiple signal transduction pathways involved in coordinating cellular responses to stress. Here we demonstrate a requirement for extracellular signal-regulated protein kinase (ERK), a member of the mitogen-activated protein kinase family in mediating cisplatin-induced apoptosis of human cervical carcinoma HeLa cells. Cisplatin treatment resulted in dose- and time- dependent activation of ERK. That elevated ERK activity contributed to cell death by cisplatin was supported by several observations: 1) PD98059 and U0126, chemical inhibitors of the MEK/ERK signaling pathway, prevented apoptosis; 2) pretreatment of cells with TPA, an activator of the ERK pathway, enhanced their sensitivity to cisplatin; 3) suramin, a growth factor receptor antagonist that greatly suppressed ERK activation, likewise inhibited cisplatin-induced apoptosis; and, finally, 4) HeLa cell variants selected for cisplatin resistance showed reduced activation of ERK following cisplatin treatment. Cisplatin-induced apoptosis was associated with cytochrome c release and subsequent caspase-3 activation, both of which could be prevented by treatment with the MEK inhibitors. However, the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone protected HeLa cells against apoptosis without affecting ERK activation. Taken together, our findings suggest that ERK activation plays an active role in mediating cisplatin-induced apoptosis of HeLa cells and functions upstream of caspase activation to initiate the apoptotic signal.     

Mechanisms of programmed cell death in the midgut and salivary glands from Bradysia hygida (Diptera: Sciaridae) during pupal–adult metamorphosis

Programmed cell death is involved with the degeneration/remodeling of larval tissues and organs during holometabolous development. The midgut is a model to study the types of programmed cell death associated with metamorphosis because its structure while degenerating is a substrate for the formation of the adult organ. Another model is the salivary glands from dipteran because their elimination involves different cell death modes. This study aimed to investigate the models of programmed cell death operating during midgut replacement and salivary gland histolysis in Bradysia hygida. We carried out experiments of real‐time observations, morphological analysis, glycogen detection, filamentous‐actin localization, and nuclear acridine orange staining. Our findings allow us to establish that an intact actin cytoskeleton is required for midgut replacement in B. hygida and nuclear condensation and acridine orange staining precede the death of the larval cells. Salivary glands in histolysis present cytoplasmic blebbing, nuclear retraction, and acridine orange staining. This process can be partially reproduced in vitro. We propose that the larval midgut death involves autophagic and apoptotic features and apoptosis is a mechanism involved with salivary gland histolysis.     

Trafficking and localization of platinum complexes in cisplatin-resistant cell lines monitored by fluorescence-labeled platinum

Cisplatin is a chemotherapeutic agent commonly used in the treatment of a wide variety of malignant tumors. Resistance to cisplatin represents a major obstacle to effective cancer therapy because clinically significant levels of resistance quickly emerge after treatment. Based on previous studies indicating abnormal plasma membrane protein trafficking in cisplatin-resistant (CP-r) cells, Fluorescence (Alexa Fluor)-labeled cisplatin was used to determine whether this defect altered the trafficking and localization of cisplatin by comparing drug sensitive KB-3-1 and KB-CP-r cells. Alexa Fluor-cisplatin was readily internalized and localized throughout the KB-3-1 cells, but overall fluorescence decreased in KB-CP-r cells, as detected by flow cytometry (FACS) and confocal microscopy. Only punctate cytoplasmic staining was observed in KB-CP-r cells with less fluorescence observed in the nucleus. Colocalization experiments with a Golgi-selective stain indicate the involvement of Golgi-like vesicles in initial intracellular processing of Alexa Fluor conjugated cisplatin complexes. As detected using an antibody to Alexa Fluor-cisplatin, cisplatin complex-binding proteins (CCBPs) were reduced in membrane fractions of single-step cisplatin-resistant KB-CP.5 cells, and increased in the cytoplasm of KB-CP.5 cells compared to KB-3-1 cells. CCBPs localized to lower density fractions in KB-CP.5 cells than in KB-3-1 cells as determined by iodixanol gradient centrifugation. In summary, inappropriate trafficking of CCBPs might explain resistance to cisplatin in cultured cancer cells, presumably because membrane binding proteins for cisplatin are not properly located on the cell surface in these cells, but are instead trapped in low density vesicles within the cytoplasm.     

Cisplatin downregulates BCL2L12, a novel apoptosis-related gene, in glioblastoma cells

Glioblastoma progression is mainly characterized by intense apoptosis resistance and marked necrosis. Over-expression of BCL2L12, a novel member of Bcl-2 family has been shown in primary glioblastoma. BCL2L12 blocks effective caspase-3/7 maturation and inhibits p53 tumor suppressor, deriving resistance toward apoptosis and inducing extensive cell necrosis. Cisplatin is a major chemotherapeutic agent which has a broad range of anti-neoplastic activities including apoptosis induction. To investigate the effect of cisplatin on the expression of BCL2L12 in glioblastoma cells, two glioblastoma cell lines were treated with different concentrations of cisplatin for 48 h. The cell viability and IC50 was determined using MTT assay. Then, the two glioblastoma cell lines were treated with 48 h IC50 concentration of cisplatin for 24, 48, and 72 h. Apoptosis induction was analyzed by fluorescence microscopy and flow cytometry. Gene expression study was performed on BCL2L12 and TBP as target and internal control genes, respectively. The quantitative real-time polymerase chain reaction results showed that BCL2L12 gene expression was significantly (p?=?0.001) downregulated in the presence of cisplatin. In conclusion, cisplatin treatment induced a time-dependent apoptosis in glioblastoma cells, at least partially via downregulation of BCL2L12 gene expression.     

Mitochondrial changes during the apoptotic process of HeLa cells exposed to cisplatin.

HeLa cells undergo apoptosis after exposure to cisplatin. Since mitochondria have recently been proposed as a probable effector of this type of cell death, we performed an analysis using the fluorescent cation rhodamine 123, which is transported actively by this organelle. Cisplatin induces a decrease in the mitochondrial staining, as assessed by cytofluorometric analysis. Microscopic analysis demonstrated that this effect was accompanied by damage of the mitochondria. These features were not exclusive of cisplatin, as other antineoplasic agents (taxol, etoposide) elicited similar effects. These results point toward the notion of a general effect of antineoplasic drugs over the mitochondria during induction of apoptotic cell death.     

The dietary isoflavone daidzein mitigates oxidative stress,apoptosis, and inflammation in CDDP‐induced kidney injury in rats: Impact of the MAPK signaling pathway

Cisplatin‐induced nephrotoxicity persists as a clinical problem despite several supportive measures to alleviate renal damage. Daidzein (DZ), a dietary isoflavone having antioxidant and anti‐inflammatory activity, is investigated in this study for protective effects against cisplatin‐induced renal injury in rats. DZ (25, 50, or 100 mg/kg; intraperitoneally; 10 days) was administered along with Cisplatin, single dose, on the 7th day of the experiment. On the 11th day, the rats were euthanized, and different samples were collected for analysis. Biochemical, histopathological, and molecular parameters were assessed to evaluate the effect of daidzein. Cisplatin injection resulted in renal dysfunction, lipid peroxidation that led to consumption of antioxidants, exaggerated apoptosis, and inflammation. These changes were associated with increase in the signaling proteins. DZ attenuated the toxic effects of cisplatin on the kidney at 100 mg/kg dose. The study concludes with the finding that daidzein imparts protection against the nephrotoxic effect of Cisplatin and can be considered as a novel, potential therapy.