The role of reactive oxidant stress on cellular damage in rabbit proximal straight tubules.

活性氧化应激对兔近端直管细胞损伤的作用。

基本信息

批准号：
08671295
负责人：
TABEI Kaoru
金额：
$ 0.64万
依托单位：
JICHI MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671295/
关键词：
Cisplatin Amino acids Microperfusion collecting duct Nephrotoxicity Glycine Glutathione acivicine Na channel K channel

项目摘要

We investigated the effect of cis-Diamminedchlotoplatinum (CDDP ; Cisplatin) on electrolyte transport in rabbit cortical collecting ci, cts, using in vitro isolated tubular microperfusion method When CDDP was applied from the luminal side, 1) CDDP hyperpolarizedtransepithelial voltage(V_T) in a dose dependencymanner from 10^<-5> M to 10^<-3> M, by inhibiting potassium channel. This effect was reversible and V_T recoveredcompletely by washing out of drugs. 2) when alanine was eliminated from the perfusate andbath medium, luminal CDDPdepolanzed VT by inhibiting both of socium and potassium channels. These data lead us to conclub that luminal CDDP inhibits both of sodum andpotassium channel by differentmechanisms, in which the inhibition of sodium channel was abolished by the presence of alanine.When CDDP was applied from the basolateral sida, 1) CDDP depolanzed VT in a cbse &pendent manner from 10^<-5> to 10^<-3> M.2) This depolarization was irreversible. 3) At aconcentrationof 10^<-4> and 10^<-3> M of CDDP, tubular swelling occurred in 60 mm and luminal membrane datachment was occurred in 90 mm. 3) When either of alanine, glycine or reduced glutathione (GSH) was added to the perfusate and bath medum, the changes of V_T was attenuated and at a concentration of 10A M CDDP, the presence of them completely abolished the depolarization. 4) However, so called antioxidant agents, such as L-NAME, catalase and dafferoxamine failed to abolished the effect of CDDP on V_T and morphological changes.In the presence of L-buthionine-S,R-sulfoximine (BSO), a GSH synthesis inhibitor, the protective effect of both glycine and GSH cid not influenced however, in the presence of acivicine, gammer-transpepticbse inhibitor, the protective effectofOSH was inhibited, and the protective effect of glycine was preserved. These findings indicated that the intracellular concentration of glycine is the determinant of the protective effect, not the concentraion of GSH.

我们使用体外分离的管状微型灌注方法调查了顺式 - 二氨基对氯丁质（CDDP;顺铂）对电解质CTS cts cts的电解质传输的影响，当m至10^<-3> m，通过抑制钾通道。这种效果是可逆的，V_T通过用药物清洗而恢复了。 2）当从灌注液和bath培养基中消除丙氨酸时，通过抑制socium and potassium通道来消除Luminal CDDPDEPOLANZED VT。这些数据导致我们得出结论，腔CDDP通过不同的机制抑制了苏um和potassium通道，在这种情况下，通过存在丙氨酸的存在消除了钠通道的抑制作用。当CDDP从基底外侧SIDA施加，1）CDDP depolanz depolanzed depolanz depolanz depolanzed tat to t t t t t to^<-5 <-5 <-5）<-5 <-5> <-5）不可逆转。 3）在10^<-4>和10^<-3> m的CDDP时，肾小管肿胀发生在60 mm中，并在90 mm中发生了腔膜datachment。 3）当将任何丙氨酸，甘氨酸或还原谷胱甘肽（GSH）添加到灌注液和浴医学上时，V_T的变化被减弱，浓度为10a m CDDP，它们的存在完全废除了去极化。 4）然而，所谓的抗氧化剂，例如L-名，催化酶和达弗羟胺，未能废除CDDP对V_T和形态学变化的影响。在L-Buthionine-S，R-硫代硫胺（R-Sulfoximine）的存在中，GSH合成抑制剂的gsh合成抑制剂和GSH的保护性效果不影响GSH CSH的保护效果固定抑制剂，抑制保护性效应，并保留了甘氨酸的保护作用。这些发现表明，甘氨酸的细胞内浓度是保护作用的决定因素，而不是GSH的浓度。