氨基胍对大鼠创伤性脑损伤的保护作用

目的探讨诱导型一氧化氮合酶（iNOS）抑制剂氨基胍（AG）对大鼠创伤性脑损伤（TBI）的神经保护作用。方法采用改进的Feeney法大鼠脑损伤模型,对生理盐水（NS）组和AG组SD大鼠于伤后6h分别腹腔注射NS或AG,每隔24h注射1次,连续注射3次。分别于致伤后24h、72h、168h取样,采用iNOS免疫组化技术,研究大鼠TBI后iNOS的表达及其细胞定位,采用凋亡细胞原位缺口末端标记法（TUNEL）,观察大鼠TBI后不同时点的神经细胞凋亡情况。结果大鼠TBI后24h,大脑损伤区周围皮质和伤侧海马iNOS阳性表达,TUNEL阳性细胞均明显增多,伤后72h表达最明显,伤后168h仍有表达;注射AG后,大脑损伤区周围皮质和伤侧海马的iNOS阳性细胞和TUNEL阳性细胞均明显减少（P〈0．01）。结论TBI后损伤区周围皮质和伤侧海马可出现iNOS阳性细胞高表达和神经细胞凋亡,且呈相关性变化,推测iNOS的过度表达可能参与了TBI后继发性神经细胞凋亡,使用AG能明显减少iNOS阳性细胞的表达和神经细胞的凋亡。     

苦碟子总黄酮对脑缺血性损伤保护作用的实验研究

目的:研究苦碟子总黄酮(TFS)对小鼠急性脑缺血和大鼠局灶性脑缺血的保护作用。方法:结扎小鼠双侧颈总动脉建立脑缺血模型,观察TFS对小鼠死亡率及死亡时间的影响。建立局灶性脑缺血(MCAO)模型,观察TFS对大鼠行为学、脑梗死范围的影响。测定脑含水量及脑组织中一氧化氮合酶(NOS)和诱导型一氧化氮合酶(iNOS)含量。结果:与模型组比较,TFS16、8 mg/kg组可降低缺血小鼠的死亡率,延长死亡时间(P<0.05,P<0.01);16、8、4 mg/kg组可改善行为障碍,降低行为学评分(P<0.05,P<0.01);105、mg/kg组可减少MCAO大鼠脑梗死范围,降低脑组织含水量及NOS和iNOS含量(P<0.05)。结论:TFS对缺血性脑损伤有保护作用,其机制可能与抑制iNOS有关。     

白藜芦醇影响一氧化氮途径对大鼠急性酒精性肝损伤的保护作用

目的 研究白藜芦醇(resveratrol,Res)对酒精性肝损伤后肝组织氧化反应和炎性反应的影响及与一氧化氮(NO)、诱导型一氧化氮合成酶(iNOS)通路的关系。方法 大鼠灌胃给予55度红星二锅头复制肝损伤模型。大鼠随机分为正常对照组、肝损伤模型对照组、Res低剂量组(25 mg·kg^-1)、Res中剂量组(50 mg·kg^-1)、Res高剂量组(100 mg·kg^-1 ),每日2次,连续7 d。采用试剂盒测定肝脏组织乳酸脱氢酶(LDH)、活性氧(ROS)、还原型谷胱甘肽(GSH)、NO、iNOS和血清IL-10、IFN-γ水平。Western blot测定iNOS表达,RT-PCR测定iNOS mRNA表达。结果 与正常对照组相比,酒精性肝损伤模型组肝组织LDH、ROS、NO浓度显著升高(P<0.01)、GSH显著下降(P<0.01),血清IFN-γ水平显著升高、IL-10显著降低(P<0.01),肝组织iNOS和iNOS mRNA表达增加(P<0.01)。与模型组相比,Res显著降低肝脏组织ROS、LDH、NO浓度(P<0.01),降低血清IFN-γ水平和升高血清IL-10与肝脏组织GSH含量(P<0.01),减少iNOS和iNOS mRNA表达(P<0.01)。结论 Res可能通过NO通路,消除氧化性应激状态,改变炎性因子水平,对酒精性肝损伤发挥防治作用。     

白藜芦醇影响一氧化氮途径对大鼠急性酒精性肝损伤的保护作用

目的研究白藜芦醇（resveratrol,Res）对酒精性肝损伤后肝组织氧化反应和炎性反应的影响及与一氧化氮（NO）、诱导型一氧化氮合成酶（iNOS）通路的关系。方法大鼠灌胃给予55度红星二锅头复制肝损伤模型。大鼠随机分为正常对照组、肝损伤模型对照组、Res低剂量组（25 mg.kg-1）、Res中剂量组（50 mg.kg-1）、Res高剂量组（100 mg.kg-1）,每日2次,连续7 d。采用试剂盒测定肝脏组织乳酸脱氢酶（LDH）、活性氧（ROS）、还原型谷胱甘肽（GSH）、NO、iNOS和血清IL-10、IFN-γ水平。Western blot测定iNOS表达,RT-PCR测定iNOS mRNA表达。结果与正常对照组相比,酒精性肝损伤模型组肝组织LDH、ROS、NO浓度显著升高（P〈0.01）、GSH显著下降（P〈0.01）,血清IFN-γ水平显著升高、IL-10显著降低（P〈0.01）,肝组织iNOS和iNOS mRNA表达增加（P〈0.01）。与模型组相比,Res显著降低肝脏组织ROS、LDH、NO浓度（P〈0.01）,降低血清IFN-γ水平和升高血清IL-10与肝脏组织GSH含量（P〈0.01）,减少iNOS和iNOS mRNA表达（P〈0.01）。结论 Res可能通过NO通路,消除氧化性应激状态,改变炎性因子水平,对酒精性肝损伤发挥防治作用。     

松花粉对急性汞中毒大鼠肝肾的保护作用及机制研究

目的研究松花粉对急性汞中毒大鼠肝肾的保护作用及机制。方法将大鼠随机均分为正常对照组,染汞模型组,松花粉低、中、高剂量组(2、4、8 g/kg)。通过皮下注射HgCl_2建立急性汞中毒模型,末次染汞后,各组分别灌胃给予相应药物,2次/d,共5 d。通过电感耦合等离子体质谱仪,测定肝汞、肾汞、血汞和尿汞的含量。通过试剂盒,测定尿素氮(BUN)、尿蛋白、尿乳酸脱氢酶(LDH)、尿碱性磷酸酶(ALP),血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、血清总胆红素(TBIL),以及肝、肾中的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、谷胱甘肽(GSH)和丙二醛(MDA)的含量或活性。结果与正常对照组比较,染汞模型组大鼠的肝汞、肾汞、血汞、尿汞、BUN、尿蛋白、尿LDH、尿ALP、血清ALT、血清AST、血清TBIL、肾脏MDA和肝脏MDA含量或活性均升高(P<0.01),肾脏和肝脏SOD、GSH-Px、GSH含量或活性降低(P<0.01)。与染汞模型组比较,松花粉低、中、高剂量组大鼠的尿汞含量增加(P<0.05或P<0.01),上述其余指标均能显著地向正常对照组的数值变化(P<0.05或P<0.01)。结论松花粉具有清除体内汞蓄积、修复急性汞中毒诱导的急性肝肾损伤的作用,其机制与抑制脂质过氧化损伤相关。     

谷氨酰胺预处理对大鼠肠缺血再灌注损伤的保护作用及其对eNOS-NO通路的影响

目的探讨谷氨酰胺(Gln)预处理对大鼠肠缺血再灌注损伤(IR)后的保护作用及其对内皮型一氧化氮合酶(e NOS)/一氧化氮(NO)信号通路的影响。方法将30只健康雄性Wistar大鼠随机分为假手术(Sham)组、IR组、Gln组,每组10只,Gln组给予谷氨酰胺1 g/(kg·d),连续灌胃7 d。Sham组和IR组以同等剂量生理盐水灌胃7 d。Sham组仅分离肠系膜上动脉(SMA)而根部不夹闭。IR组和Gln组均用无损伤血管夹夹闭SMA根部,30 min后放松血管夹形成再灌注损伤模型。各组大鼠均于制模后24 h采集腹主动脉血和回肠标本。应用HE染色法观察肠黏膜组织形态学改变,ELISA试剂盒双抗体夹心法测定D-乳酸、内毒素含量,硝酸还原酶法检测血清NO的含量,比色法检测血清e NOS、诱导型一氧化氮合酶(i NOS)的含量,荧光定量PCR(RT-PCR)检测大鼠肠组织e NOS、i NOS m RNA表达水平。结果再灌注后,与Sham组相比,IR组肠黏膜绒毛上皮脱落,固有层崩解,部分绒毛顶端出血,腺体明显受损;Gln组表现为肠黏膜绒毛上皮下间隙扩大,但不明显,绒毛轻度水肿,腺体大致正常,固有层轻度水肿。IR组血清D-乳酸、内毒素、i NOS水平及肠组织i NOS m RNA表达水平均高于Sham组和Gln组(P<0.05)。IR组血清NO、e NOS含量及组织中e NOS的m RNA表达量均低于Sham组和Gln组(P<0.05)。结论谷氨酰胺预处理可以减轻肠缺血再灌注后的组织形态学改变及损伤,其机制可能与抑制i NOS表达,增加e NOS表达,从而增加NO活性有关。     

NO和iNOS在大鼠糖尿病早期肾脏中的变化

目的:观察糖尿病大鼠早期肾脏中一氧化氮(Nitric oxide,NO)含量和诱导型一氧化氮合酶(Inducible nitric oxide syn-thase,iNOS)活性变化,探讨NO/iNOS在糖尿病早期肾脏损害中的作用机制。方法:取成年健康SD大鼠60只,随机分成糖尿病组(DM组)和正常对照组(NC组),每组30只。DM组大鼠采用一次性腹腔内注射STZ制造糖尿病大鼠模型,成模后和NC组分别于第1、2、4周麻醉取左肾,用硝酸还原酶法和吸光光度法测定肾组织中NO含量、一氧化氮合酶(nitric oxide synthase,NOS)和iNOS活性。所有数据用SPSS11.5统计软件进行统计学处理。结果:①DM组大鼠肾组织中NO含量、NOS和iNOS活性分别较同批NC组有显著性差异(P<0.05);②各组大鼠中NO含量与NOS活性、iNOS活性呈正相关。结论:糖尿病大鼠早期肾脏中iNOS活性增强,催化生成的NO在糖尿病早期肾脏损害中发挥重要作用。     

重组人促红细胞生成素对大鼠肝脏缺血-再灌注损伤的保护作用

目的探讨重组人促红细胞生成素(rHuEPO)对大鼠肝脏缺血-再灌注(I-R)损伤的保护作用。方法将30只大鼠随机均分为假手术组(A组)、I-R模型组(B组)和rHuEPO 5000IU/kg处理组(C组)。建立70%大鼠肝脏I-R损伤模型,检测各组血清ALT、AST水平,HE染色观察组织学变化,Western blot及RT-PCR检测肝脏诱导型一氧化氮合酶(iNOS)和内皮型一氧化氮合酶(eNOS)的表达。结果与B组相比,C组iNOS mRNA和蛋白表达、ALT和AST水平均明显减少(P<0.05或P<0.01),肝细胞水肿、坏死减轻;而B组和C组间eNOS mRNA和蛋白表达差异无统计学意义(P>0.05)。结论 rHuEPO可能通过抑制iNOS表达,减轻大鼠肝脏I-R损伤。     

孕三烯酮对子宫内膜异位症大鼠血清中iNOS作用的研究

目的观察孕三烯酮对子宫内膜异位症（EMs）大鼠模型血清诱导型一氧化氮合酶（iNOS）的影响。方法采用自体子宫内膜移植法建立EMs大鼠模型,造模成功者随机分为模型组、孕三烯酮组,分别灌胃给药,4周后择动情期处死。采用比色法检测血清iNOS活性。结果模型组与孕三烯酮组相比较,血清中iNOS明显降低,差异有统计学意义（P〈0.01）。结论孕三烯酮能降低EMs大鼠血清中iNOS活性,从而降低NO水平,抑制异位内膜的种植、生长。     

花椒毒酚对重症急性胰腺炎大鼠脑损伤保护作用及NF-κB/iNOS通路的影响

目的探讨花椒毒酚对重症急性胰腺炎(SAP)大鼠脑损伤的保护作用及对核因子-κB/诱导型一氧化氮合酶(NF-κB/iNOS)通路的影响。方法将64只Wistar大鼠随机分为8组:正常对照3 h组、12 h组,模型3 h组、12 h组,花椒毒酚低剂量(5 mg/kg)3 h组、12 h组,花椒毒酚高剂量(10 mg/kg)3 h组、12 h组,每组8只;采用5%牛黄胆酸钠(2 mL/kg)注入胰胆管进行SAP造模,正常对照组为假手术组。于术后3、12 h收集各组大鼠腹主动脉血、胰腺组织和脑组织,观察各组大鼠胰腺组织和脑组织HE染色评分;检测各组大鼠血浆淀粉酶、NO、NF-κB p65水平及脑组织含水量、神经功能评分、NF-κB p65、iNOS蛋白相对表达量。结果模型组大鼠术后3、12 h胰腺组织HE染色评分、血浆淀粉酶均较对照组明显升高(P<0.05),花椒毒酚高、低剂量组胰腺组织HE染色评分、血浆淀粉酶均较模型组明显降低(P<0.05),且高剂量组各指标均明显低于低剂量组(P<0.05);模型组大鼠术后3、12 h脑组织HE染色评分、脑组织含水量、神经功能评分均较对照组明显升高(P<0.05),花椒毒酚高低剂量组胰腺组织、脑组织HE染色评分、脑组织含水量、神经功能评分均较模型组明显降低(P<0.05),且高剂量组各指标均明显低于低剂量组(P<0.05);模型组大鼠术后3、12 h血清NO、NF-κB p65水平及脑组织NF-κB p65、iNOS水平均明显高于对照组(P<0.05),花椒毒酚高、低剂量组各指标均较模型组明显降低(P<0.05),且高剂量组各指标下降幅度尤为明显(P<0.05)。结论花椒毒酚能够通过降低SAP大鼠脑组织NF-κB、iNOS蛋白表达,发挥对大鼠脑损伤的保护作用。     

Protective effect of γ-aminobutyric acid against glycerol-induced acute renal failure in rats

To investigate the effect of γ-aminobutyric acid (GABA) on acute renal failure, we used a rat model of acute tubular necrosis induced by glycerol. After deprivation of water for 6 h, the rats received an injection of 50% glycerol into the muscle of the rear limb at 10 ml/kg body weight. GABA was then administered orally to the rats (100 or 500 mg/kg body weight/day) once every 12 h for 3 days. The rats with acute renal failure showed arrested body weight gain and an increase of kidney weight, whereas oral administration of GABA attenuated the physiological changes induced by acute renal failure. However, GABA administration had no significant effect on increased urine volume. Oral administration of GABA at a dose of 100 or 500 mg/kg body weight/day for 3 days significantly improved the markedly elevated levels of blood urea nitrogen and creatinine and the reduced creatinine clearance related to progression of renal failure. Moreover, the rats with acute renal failure exhibited high levels of fractional excretion of sodium (FE_Na) due to alteration of tubule function following injection of glycerol. However, administration of GABA lowered the FE_Na levels dose-dependently. Furthermore, urine osmolarity was markedly reduced in control rats with acute renal failure as compared with normal rats, whereas it was significantly increased by administration of GABA at a dose of 500 mg/kg body weight/day. These results indicate that GABA has potential as a therapeutic agent against the renal damage involved in acute renal failure.     

Effect of uranyl nitrate-induced acute renal failure on the pharmacokinetics of sulfobromophthalein in rats

The effect of acute renal failure (ARF) on the pharmacokinetics of sulfobromophthalein (BSP) was investigated in order to elucidate if renal failure modifies the hepatic metabolism of drugs. ARF was induced by intravenous (iv) injection of uranyl nitrate (UN) to rats (5 mg/kg) five days before the experiment. Area under the plasma concentration-time curve (AUC) of BSP after portal vein (pv) injection increased by 2-fold and total body clearance (CL _t) decreased one half (p<0.01) in UN-induced ARF (UN-ARF) rats compared to the control rats. But the plasma disappearance of BSP afteriv injection did not differ significantly between control and UN-ARF rats. Since BSP is excretedvia the liver,CL _t representd the approximate hepatic clearance of BSP. Therefore, the decrease inCL _t represents a decrease in hepatic intrinsic clearance (CL _int) for BSP since plasma free fraction (f _p) of BSP was not affected by UN-ARF. The content of hepatic cytoplasmic Y-protein, which catalyzes BSP-glutathione conjugation and limits the transfer of BSP from blood to bile, increased significantly (p<0.01), however its binding activity (BA) for BSP was decreased significantly (p<0.01) by UN-ARF. The decrease inCL _int might have some correlation with the changed characteristics of hepatic Y-protein, specifically its decreased BA for BSP.     

Protective role of phosphatidylcholine against cisplatin-induced renal toxicity and oxidative stress in rats

Although cisplatin is widely used in the treatment of cancers, clinical use of cisplatin is limited due to its nephrotoxicity. Pathophysiological mechanism of cisplatin-induced renal toxicity is a complex process and has not been fully understand. Reactive oxygen species (ROS) and oxidative stress have been presumed to be involved in this damage process. Phosphatidylcholine (PC) has antioxidant effect and prevents oxidative stress. Therefore, the present study aimed to investigate potential protective effects of PC on cisplatin-induced renal damage in rat. We examined the protective effects of PC on cisplatin-induced renal damage by assessment of serum creatinine, BUN, lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, superoxide dismutase activity and histophathological changes. PC ameliorated cisplatin-induced increases in serum creatinine, urea and oxidative stress. PC also decreased tubular degeneration and hypertrophy of glomeruli. PC may have a protective effect against cisplatin-induced nephrotoxicity in rats via enhancing antioxidant enzyme activity.     

虫草多糖对庆大霉素诱发的急性肾衰的预防作用

目的：探讨虫草多糖对庆大霉素诱发的急性肾衰的防治作用。方法：将实验动物分为阳性地塞米松磷酸钠组,虫草多糖高、中、低剂量组以及正常对照组、模型组;采用腹腔注射庆大霉素的方法复制大鼠急性肾衰（ARF）模型,造模过程中预防给药。观察大鼠的血液生化指标、肾功能、肾病理、肾指数等指标的变化。结果：预防给药后,阳性对照组和虫草多糖3个剂量组大鼠的血清尿素氮、肌酐的含量,以及尿蛋白和尿量降低,与模型组比较有显著差异（P〈0．01或P〈0．05）,高剂量和中剂量虫草多糖的作用优于阳性对照组。病理切片可见阳性对照组和虫草多糖高剂量组大鼠肾脏病理损伤明显好转,优于中、低剂量组。结论：虫草多糖能够预防大鼠庆大霉素诱发的急性肾衰,改善肾功能。     

277例急性肾功能衰竭患者流行病学研究

目的总结本院急性肾功能衰竭患者的流行病学特征,为早期防治提供临床证据。方法回顾性分析研究。分析患者一般资料、临床检验指标、治疗措施及预后。结果277例病例,男、女比例约为2：1。平均住院（20．01±19．08）d,平均（48．31±20．62）岁。实验室指标：平均血红蛋白（114±25）g/L,平均峰值血肌酐（445．4±312．1）μmol／L,平均峰值血尿素氮（23．05±9．88）mmol／L,少尿（含无尿）期为1-64d,平均5．94d;多尿期1～54d,平均2．82d。不同年龄组间住院天数及治疗效果比较,P〈0．05。结论本院急性肾功能衰竭占同期住院患者的比例为1．8‰。病因以肾性因素居多。老年患者以结石等肾后性因素多见,非老年患者以急性肾小管坏死、肾病综合征等肾实质性因素常见。少尿型ARF以急性肾小管坏死（ATN）多见,非少尿型ARF以药物多见。     

Protective effects of FK453, a potent nonxanthine adenosine A1 receptor antagonist,on glycerol-induced acute renal failure in rats

The purpose of the present study was to examine the protective effect of FK453, (+)-(R)-1-[(E)-3-(2-phenylpyrazolo [1,5-a] pyridin-3-yl) acryloyl]-2-piperidine ethanol, a potent non-xanthine (adenosine A₁ receptor antagonist, on glycerol-induced acute renal failure (ARF) in rat in comparison with the effects of FR113452 (S-(-) enantiomer of FK453), 1,3-dipropyl-8-cyclopentyl-xanthine (adenosine A₁ receptor antagonist), theophylline (nonselective adenosine receptor antagonist), CGS15943 [1,2,4] triazolo [1,5-C] quinazolone, adenosine A_2A receptor antagonist), and typical diuretics (hydrochlorothiazide and furosemide). FK453 (1 and 10 mg/kg orally) significantly reduced serum creatinine and urea concentrations in 25% glycerol (10 ml/kg intramuscularly)-induced ARF by protective treatment. The effect was similar to that of 1,3-dipropyl-8-cyclopentyl-xanthine and theophylline. FR113452 and CGS15943 had little effect on serum creatinine and urea concentrations. In contrast, hydrochlorothiazide and furosemide increased serum creatinine and urea concentrations. FK453, hydrochlorothiazide, and furosemide did not have any effect on either serum creatinine or urea concentration in 25% glycerol-induced ARF by therapeutic treatment. In 50% glycerol (10 ml/kg im)-induced ARF, FK453 reduced serum creatinine and urea concentrations, and increased urine volume and creatinine clearance. The results of the present study showed that FK453, a potent nonxanthine adenosine A₁ receptor antagonist, ameliorated glycerol-induced ARF in the rat. The findings support the idea that adenosine is an important factor in the development of glycerol-induced ARF in the rat and that the protective effect of adenosine receptor antagonist is mediated via the adenosine A₁ receptor. Drug Dev. Res. 39:47–53 © 1997 Wiley-Liss, Inc.     

Pharmacological investigations of Punica granatum in glycerol-induced acute renal failure in rats

Objective:

The present study was designed to investigate the ameliorative potential and possible mechanism of hydroalcoholic extract of flowers of P. granatum in glycerol-induced acute renal failure (ARF) in rats.

Materials and Methods:

The rats were subjected to rhabdomyolytic ARF by single intramuscular injection of hypertonic glycerol (50% v/v; 8 ml/kg) and the animals were sacrificed after 24 hours of glycerol injection. The plasma creatinine, blood urea nitrogen, creatinine clearance, and histopathological studies were performed to assess the degree of renal injury.

Results:

Pretreatment with hydroalcoholic extract of flowers of P. granatum (125 and 250 mg/kg p.o. twice daily for 3 days) significantly attenuated hypertonic glycerol-induced renal dysfunction in a dose-dependent manner. BADGE (Bisphenol-A-diglycidyl ether) (30 mg/kg), a peroxisome proliferator-activated receptor (PPAR)-γ antagonist, and N(omega)-nitro-l-arginine-methyl ester (L-NAME) (10, 20, and 40 mg/kg), nitric oxide synthase inhibitor, were employed to explore the mechanism of renoprotective effects of Punica granatum. Administration of BADGE (30 mg/kg) and L-NAME (40 mg/kg) abolished the beneficial effects of P. granatum in glycerol-induced renal dysfunction.

Conclusion:

Hydroalcoholic extract of flowers of P. granatum has ameliorative potential in attenuating myoglobinuric renal failure and its renoprotective effects involve activation of PPAR-γ and nitric oxide-dependent signaling pathway.     

汉防已甲素对大鼠急性缺血性肾衰的保护作用

目的 研究汉防已甲素对急性缺血性肾衰的保护作用。方法 术前 ３ｄ开始每天 １次及术前 １ｈ ｉｇ汉防已甲素 ２０ｍｇ／ｋｇ、４０ ｍｇ／ｋｇ。然后制作大鼠肾脏缺血再灌注致急性缺血性肾衰模型，测定肾组织中 ＭＤＡ、ＳＯＤ、Ｎａ＋，Ｋ＋－ＡＴＰ酶和Ｃａ２＋－ＡＴＰ酶含量及切片观察肾脏形态。结果 缺血6０ｍｉｎ再灌注２０ｍｉｎ后肾组织中 ＭＤＡ明显升高，ＳＯＤ、Ｎａ＋、Ｋ＋－ＡＴＰ酶和 Ｃａ２＋－ＡＴＰ酶均显著降低。用药组 ＭＤＡ显著下降，ＳＯＤ和 ＡＴＰ酶均明显升高。病理结果提示再灌注组肾小管上皮明显变性，而用药组损害明显减轻。结论 汉防已甲素对急性缺血性肾衰有一定的保护作用。     

Protective effect of alpha-lipoic acid against ischaemic acute renal failure in rats

1. In the present study, we investigated whether treatment with alpha-lipoic acid (LA), a powerful and universal anti-oxidant, has renal protective effects in rats with ischaemic acute renal failure (ARF). 2. Ischaemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Blood urea nitrogen (BUN), plasma concentrations of creatinine (Pcr) and urinary osmolality (Uosm) were measured for the assessment of renal dysfunction. Creatinine clearance (Ccr) and fractional excretion of Na+ (FENa) were used as indicators of glomerular and tubular function, respectively. 3. Renal function in ARF rats decreased markedly 24 h after reperfusion. Intraperitoneal injection of LA at a dose of 10 mg/kg before the occlusion tended to attenuate the deterioration of renal function. A higher dose of LA (100 mg/kg) significantly (P < 0.01) attenuated the ischaemia/reperfusion-induced increases in BUN (19.1 +/- 0.7 vs 7.2 +/- 0.7 mmol/L before and after treatment, respectively), Pcr (290 +/- 36 vs 78.1 +/- 4.2 micromol/L before and after treatment, respectively) and FENa (1.39 +/- 0.3 vs 0.33 +/- 0.09% before and after treatment, respectively). Treatment with 100 mg/kg LA significantly (P < 0.01) increased Ccr (0.70 +/- 0.13 vs 2.98 +/- 0.27 mL/min per kg before and after treatment, respectively) and Uosm (474 +/- 39 vs 1096 +/- 80 mOsmol/kg before and after treatment, respectively). 4. Histopathological examination of the kidney of ARF rats revealed severe lesions. Tubular necrosis (P < 0.01), proteinaceous casts in tubuli (P < 0.01) and medullary congestion (P < 0.05) were significantly suppressed by the higher dose of LA. 5. A marked increase in endothelin (ET)-1 content in the kidney after ischaemia/reperfusion was evident in ARF rats (0.43 +/- 0.02 ng/g tissue) compared with findings in sham- operated rats (0.20 +/- 0.01 ng/g tissue). Significant attenuation (P < 0.01) of this increase occurred in ARF rats treated with the higher dose of LA (0.24 +/- 0.03 ng/g tissue). 6. These results suggest that administration of LA to rats prior to development of ischaemic ARF prevents renal dysfunction and tissue injury, possibly through the suppression of overproduction of ET-1 in the postischaemic kidney.     

Protective effects of L-carnitine on myoglobinuric acute renal failure in rats

1. Muscle injury (rhabdomyolysis) is one of the causes of acute renal failure (ARF). Iron, free radicals and nitric oxide (NO) play a critical role in the pathogenesis of glycerol-induced myoglobinuric ARF. L-Carnitine is an anti-oxidant and prevents the accumulation of end-products of lipid peroxidation. Therefore, the aim of the present study was to investigate the effects of L-carnitine on myoglobinuric ARF induced by intramuscular (i.m.) hypertonic glycerol injection. 2. Sprague-Dawley rats were divided into three groups. Rats in group 1 (n = 8) were given saline, whereas those in groups 2 (n = 10) and 3 (n = 10) were injected with glycerol (10 mL/kg, i.m.). Concomitant with and 24 h after glycerol injection, L-carnitine (200 mg/kg, i.p.) was administered to group 3 rats. Forty-eight hours after glycerol injection, blood samples and kidney tissues were taken from anaesthetised rats. 3. Plasma creatine kinase (CK) activity, urea, creatinine and NO levels, as well as kidney tissue superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzyme activity and malondialdehyde (MDA) and glutathione (GSH) levels, were determined. In the kidney tissue, histopathological changes and iron accumulation in the tubular epithelium were also investigated. 4. Glycerol treatment caused severe ARF: a marked renal oxidative stress, significantly increased CK activity, urea and creatinine levels and decreased plasma NO levels. Histopathological findings in group 2 rats confirmed that there was renal impairment by cast formation and tubular necrosis and a marked increase in iron accumulation in the tubular epithelium. All these factors were significantly improved by L-carnitine supplementation. 5. These results may indicate that L-carnitine treatment protects against functional, biochemical and morphological damage and iron accumulation in glycerol-induced myoglobinuric ARF in rats. In this model, the protective effect of L-carnitine treatment may provide a new insight into the treatment of rhabdomyolysis-related ARF.