Curcumin against cisplatin nephrotoxicity and its mechanism_440

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Curcumin against cisplatin nephrotoxicity and its mechanism_440

Curcumin against cisplatin nephrotoxicity and its mechanism

     Author: Ying Huang Rong-yi Wang Shunrong

     Abstract Objective To investigate curcumin (CMN) Anti-

    cisplatin-induced renal injury and its mechanism. Methods 48

    male Wistar rats were randomly divided into ? (n = 12), ? (n

    = 6), ? (n = 6), ? (n = 12), ? (n = 12) groups, each row

    1st intraperitoneal injection of: saline (?, ?, ? group),

    CMN 30 mg / kg (? group), CMN 30 mg / kg of zinc

    protoporphyrin ? (ZnPP ?) 10 mg / kg (? group), 8 h, from

    the ?, ?, ? group of six rats each were killed optional testing HO 1 protein expression and vitality. I mouse again the 2nd intraperitoneal injection of: saline (? group), CMN

    20 mg / kg of cisplatin 6 mg / kg (? group). Cisplatin 6 mg /

    kg (?, ?, ? group), 5 d after the execution, testing serum creatinine (Cr), blood urea nitrogen (BUN), kidney coefficient, kidney tissue superoxide dismutase (SOD) activity and glutathione GSH (GSH) and malondialdehyde (MDA) content. The results of cisplatin can significantly increase the level of oxidative stress in renal tissue and a serious injury in the kidney structure and function of curcumin only a weak direct anti-cis-platinum renal toxicity, but the pretreatment with curcumin increases HO 1 protein expression and

    activity can significantly enhance its anti-cis-platinum renal

    toxicity; On the contrary, with ZnPP ? inhibiting HO 1

    activity of curcumin could be the elimination of anti-cis-

    platinum renal toxicity. Conclusion Curcumin mainly through

    increases HO 1 protein expression in an effective

    antagonist of cisplatin-induced oxidative stress-induced renal


     Key words Cisplatin; curcumin; of heme oxygenase- 1;

    oxidative stress; renal toxicity

     Study on the Protective Effect and Mechanism of Curcumin on Cisplatin induced Nephrotoxicity

     Abstract: Objective To investigate the protective effects of curcumin (CMN) on cisplatin induced nephrotoxicity in

    rats and the possible mechanisms. Methods48 male wistar rats

    were randomly divided into 5 groups: groupI (n = 12), groupII (n = 6), groupIII (n = 6), groupIV (n = 12), groupV (n = 12). Rats received intraperitoneally injection for the first time respectively with saline (groupI, groupII, groupIII), CMN 30 mg / kg (groupIV), CMN 30 mg / kg Zinc protoporphyrin IX (ZnPPIX) 10 mg / kg (groupV) .8 hours later, half rats in group I, groupIV, groupV were killed to analyse renal HO 1

    protein express and activity.Other rats received the intraparitoneally injection for the second time respectively

    with saline (groupI), Cisplatin 6mg/kg CMN 30 mg / kg (groupIII) and cisplatin 6 mg / kg (groupII, groupIV, groupV) .5 days later, all the animals were killed to measure the blood creatinin (Cr), urea nitrogen (BUN) and analyse the

    renal superoxide dismutase (SOD) activity, glulathion (GSH) and malondialdehyde (MDA) content and histopathological lesion.ResultsCisplatin could increase the renal oxidative stress level and damage seriously the renal histology construction and function.CMN only has slight direct

    protective effect against the cisplatin-induced

    nephrotoxicity.But the renal protective effect would increased significantly by pretreatment with CMN to up regulate renal

    HO 1 protein level and considerably attenuated by inhibiting HO 1 protein activity with ZnPP ?.

    ConclusionCMN can protect against cisplatin induced

    oxidative stress renal injury by inducing HO 1.

     Key words: Cisplatin; Curcumin; Heme oxygenase 1;

    Oxidative stress; Nephrotoxicity

     Cisplatin is currently the clinical, one of the most commonly used anticancer drugs, such as lung cancer, bladder cancer, testicular cancer and ovarian cancer, such as more

    than ten kinds of cancer chemotherapy was recommended as the preferred drug, but the apparent renal toxicity of cisplatin to a large extent would restrict its clinical application. In

recent years, studies have reported that curcumin (curcumin,

    CMN) can effectively prevent cisplatin-induced acute renal

    injury, but its mechanism has not been fully clarified [1]. In view of cisplatin is mainly through the promotion of free radicals causing oxidative stress suffered kidney damage [2], while heme oxygenase 1 (HO 1) is the cellular response

    to oxidative stress injury in a variety of the most important endogenous protection factor, so we speculated that CMN may be expressed through induction of HO 1 as an anti-cis-platinum

    renal toxicity, but has yet to see a related research reports at home and abroad. This article intends to make a study of this.

     1 Materials and methods

     1.1 Drugs and reagents cisplatin Bio-Pharmaceutical Co.,

    Ltd. Yunnan old product, batch number: 060,701. Zinc

    protoporphyrin ? (ZnPP ?) and CMN were purchased in Sigma

    Corporation. Creatinine (Cr), blood urea nitrogen (BUN), superoxide dismutase (SOD) and protein quantitative detection kit purchased from Nanjing Jiancheng Bio-Engineering

    Institute. HO 1 Immunohistochemical detection of antibodies and reagents purchased from Wuhan Boster Company.

     1.2 Animal grouping and treatment options 48 healthy male Wistar rats weighing 185 ~ 230 g, were randomly divided into five groups: ? group (control group, n = 12), ? group

    (cisplatin alone group, n = 6) , ? group (CMN group, n = 6),

    ? group (CMN preconditioning group, n = 12), ? group (HO

    1 suppression group, n = 12). Respectively, the 1st volume of normal saline via intraperitoneal injection, etc. (?, ?, ?

    group), CMN 30 mg / kg (? group), CMN 30 mg / kg ZnPP ? 10

    mg / kg (? group), 8 h later, from the ?, ?, ? 3 groups of

    6 rats were killed either pick to take kidney detected HO 1

    protein expression and vitality. The remaining rats each with the 2nd through the abdominal cavity with normal saline (?

    group), CMN 30 mg / kg of cisplatin 6 mg / kg (? group),

    cisplatin 6 mg / kg (?, ?, ? group). Usual eating animals

    such as free photo of water, 5 d, after weighing, were killed, and renal blood testing of indicators.

     1.3 Index Detection

     1.3.1 HO 1 were detected by SABC was detected in renal

    tissue HO 1 protein expression. Renal tissue in 10% neutral formalin fixed, paraffin-embedded, cut, sliced conventional

    dewaxing, to water, 3% H2O2 inactivation of endogenous peroxidase, after antigen retrieval, the normal serum is closed, ? dropping anti-(anti-HO 1 antibody titer of

    1:200) and anti-? (titer 1:100), DAB color dark at room

    temperature, dehydration, transparent, Fengpian, observed under the microscope, see the cytoplasm there brown granules were as HO 1 positive cells, using CD 8 pathological

    color image analysis system at 200 times the light microscope, on each slice were randomly determined 10 not repeat the vision of renal tubular epithelial cells HO 1 protein,

    optical density value, averaged on behalf of HO 1 protein


     HO 1 activity assay reference to Yao Wood [3] methods, that is, to take kidney organize about 0.5 g, made of 10% tissue homogenate, high-speed centrifugation microsomal, test Ma Liang Lan quantitative protein concentration, and then under the HO 1 degradation of blood-red The principle

    elements of bilirubin generated by measuring the formation of bilirubin in the reaction system on behalf of HO 1 the

    amount of energy, units of nmol / (mg protein h).

     1.3.2 serum Cr, BUN and kidney biochemical parameters

    were measured according to kit instructions were used picric acid method, Determination of diacetyl blood Cr, BUN. Said the kidneys weight, per 100 g kidney weight, the weight of the corresponding coefficient of his kidneys. Take about 1 g renal

    cortex tissue homogenate is made, according to kit instructions steps measured SOD activity (xanthine oxidase), GSH (dithio-p-nitrophenyl France), and MDA content

    (thiobarbituric France ).

     1.4 Histopathological examination taken place small piece

    of kidney tissue in 10% neutral formalin fixed, regular alcohol, dimethyl benzene dehydration, embedded in paraffin, sliced, HE staining, light microscope observation of morphological change.

     1.5 Statistical analysis of data obtained in this experiment are the measurement data in order to (? s) that

    was used to compare between the two groups F q test, using statistical software to complete SPSS11.0. Reposted elsewhere in the paper for free download http://

     2 Results

     2.1 kidney HO 1 protein expression and dynamic changes in immunohistochemical analysis showed that, HO 1 protein

    was mainly expressed in the cytoplasm of renal tubular epithelial cells, where the basis of group ?, on behalf of

    the state, showing rat kidney HO 1 protein expression

    volume and activity were lower. ?, ? group had no testing,

    but pretreatment with the group ?, so the HO 1 protein

    expression and activity should be the same as in group ?. ?

    group showed a significant increase in pre-CMN renal HO 1

    protein expression and activity. ? group showed ZnPP ?

    partially inhibited the CMN-induced HO 1 protein expression and significantly inhibited the HO 1 activity. Figure 1 and Table 1.

     Table 1 HO 1 protein expression and activity of the comparison (omitted)

     Compared with group ?, * P

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