肾提取液对大鼠庆大霉素肾毒性的防治作用研究

研究乳猪肾提取液对大鼠庆大霉素肾毒性的防治作用。新鲜乳猪肾经匀浆、超滤等处理得肾提取液。肌注庆大霉素100mg／（kg·d）×7d制成大鼠急性肾衰模型。制模同时及造模后分别ip肾提取液15mg／（kg·d）,观察大鼠血清尿素氮（Bloodureanitrogen,BUN）、肌酐（Cr）及肾组织变化情况。实验结束时,预防组BUN为9．30±2．60mmol/L,Cr为125．00±26．60μmol／L;模型组BUN为12.80±2.45mmol／L,Cr为167．00±39．60μmol／L,P＜0．01。结果表明,肾提取液可明显减轻庆大霉素对大鼠的肾损害。     

Bioassay for Carcinogenicity of Rotenone in Female Wistar Rats

Rotenone, a pesticide extracted from the Derris root, consistentlywas reported by a series of investigators to have induced mammaryfibroadenomas in female Wistar rats when administered ip orby gavage in a sunflower (SF) oil or SF oil:chloroform vehicle.In contrast, no less than eight bioassays done in other laboratorieswith rotenone or rotenone-containing powders have given consistentlynegative carcinogenic results when different strains or speciesand different modes or vehicles of administration have beenused. However, these studies were not designed to address thebiological reproducibility of the positive data. Thus, the presentstudy was designed to simulate conditions of the positive studiesand to investigate a possible cocarcinogenic interaction betweenrotenone and chloroform. Each of eight treatment groups wasassigned 72 weanling female Wistar rats. Groups were (1) untreated,(2) needle puncture, (3) SF oil: 10% chloroform (SF oil:chloroform),(4) 1.0 mg/kg rotenone in SF oil:chloroform, (5) 2.0 mg%kg rotenonein SF oil:chloroform, (6) SF oil, (7) 1.0 mg/kg rotenone inSF oil, and (8) 2.0 mg/kg rotenone in SF oil. Rats were injectedip 5 days a week for 8 weeks (42 injection days) and subsequentlyheld for 16 months. The appearance of palpable tissue masseswas recorded; over 50 tissues from each rat were histologicallyevaluated. There were no statistically significant differencesin overall or individual tumor incidences among control androtenone treated groups. Specifically, neither incidence nortime-to-palpation of mammary fibroadenoma significantly differedamong control and rotenone-treated groups, regardless of thevehicle of administration. Thus, rotenone was not carcinogenic,and rotenone and chloroform did not interact to produce a carcinogeniceffect in female Wistar rats in the current study. Thus, previousreports of carcinogenic activity were not reproducible undersimilar experimental conditions.     

Time Course of Chronic Oral Cadmium Nephrotoxicity in Wistar Rats: Excretion of Urinary Enzymes

ABSTRACT

Twelve male and female Wistar rats each received cadmium (as CdCl₂) in their diet at concentrations of 0, 10, 50, and 250 ppm for 72 weeks. After 1, 4, 8, 13, 18, 26, 32, 45, 57, and 68 weeks a total of 8 enzymes from different cellular compartments of the nephron were measured. At the end of the study period, the kidneys were examined histopathologically.

Concentrations up to and including 50 ppm did not induce any adverse effect. At 250 ppm, growth of male and female animals was markedly retarded. Significantly increased activities of the cytosolic phosphohexose isomerase were excreted by males and females receiving 250 ppm at all timepoints from week 13. The values of the mitochondrial glutamate dehydrogenase were mostly elevated from week 1 to 57, however, due to a wide scatter range, were only occasionally significantly different from control values. The brush border enzymes (gamma-glutamyl transferase, alkaline phosphatase and leucine arylamidase) were not changed in a relevant manner in female rats, while in 250 ppm males the excreted activity of ALP and LAP from week 1 to week 18, and that of GGT during the entire study period were significantly lower than the control values. Excretion of the lysosomal enzymes aryl sulfatase A, beta-galactosidase, and beta-N-acetyl-D-glucosaminidase was at no time influenced in a noteworthy manner.

Histopathology after 72 weeks revealed chronic but also acute degenerative changes in the kidneys of 250 ppm males and females.

A comparison of published data on persons having undergone high cadmium exposure with the results presented here shows remarkable differences.     

Comparative Nephrotoxicity of a Novel Platinum Compound, Cisplatin, and Carboplatin in Male Wistar Rats

The nephrotoxicity of three platinum-containing antitumor agentswas compared at doses that approximate the LDIO (cisplatin)or the LD5O (CI-973, carboplatin) doses. Male Wistar rats wereadministered single iv doses of 45 mg/kg CI-973, 6.5 mg/kg cisplatin,or 65 mg/kg carboplatin and observed for 4 days. Cisplatin treatmentincreased blood urea nitrogen (4X), creatinine (3x), glucose,and fractional electrolyte excretions, and decreased creatinineclearance by Day 4. These parameters were not significantlyaltered in CI-973- and carhoplatin-treated animals. Cisplatinincreased urinary excretion of LDH (six fold), GGT (twofold),and NAG (twofold); CI-973 and carbo platin increased GGT excretion(approximately twofold). Cis platin induced the following functionalchanges as a conse quence of direct nephrotoxicity: decreasesin GFR (84%), ERPF (97%), ERBF (96%), and ERTS (95%), and increasesin FF (fivefold). Functional changes, attributed to prerenaleffects of CI-973, included a decrease in ERPF (35%) and anincrease in FF (48%). No changes were seen following carboplatintreat ment. All cisplatin-treated rats had proximal tubularnecrosis in the outer stripe of the outer medulla, extendingmultifocally into inner cortical medullary rays. No renal lesionswere de tected by light or electron microscopy in the controlor Cl-973- or carboplatin-treated rats. Cisplatin produced markednephro toxicity as determined by biochemical, functional, andhisto pathologic endpoints. CI-973 and carboplatin were significantlyless nephrotoxic than cisplatin.     

Hematological and Clinical Chemistry Changes Induced by Subchronic Dosing of a Novel Phosphorothionate (RPR-V) in Wistar Male and Female Rats

A novel phosphorothionate [2-butenoic acid-3-(diethoxy phosphinothioyl)-ethyl ester; RPR-V] synthesized at Indian Institute of Chemical Technology (Hyderabad, India) was studied using subchronic doses of 0.033 (low), 0.066 (medium), and 0.099 (high) mg kg^{? 1} in male and female rats daily for 90 days. Continuous treatment with RPR-V caused significant (p < 0.05) decreases in body-weight gain, feed intake, hemoglobin (Hb), hematocrit (Hct), and total erythrocyte count (TEC), whereas total leukocyte count (TLC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were increased. Similarly, RPR-V caused significant elevation in serum clinical chemistry parameters calcium, phosphorus, creatinine, and chloride contents, whereas protein and glucose levels were depressed in both male and female treated rats after 45 and 90 days of treatment. These alterations were significant when compared with two-way ANOVA showing that these changes were dose- and time-dependent. The effects of low dose were generally not statistically significant, whereas medium and high doses caused significant effects. The changes in male rats were not significant when compared with female rats showing no sexual dimorphism by this compound. Recovery was observed after 28 days post-treatment (withdrawal study), indicating that the compound entered into the system was eliminated from the body, and the blood parameters were improved. Hematological and clinical chemistry parameters can be detected rapidly and hence can be used for prediction and diagnosis of pesticide toxicity. Alterations in these parameters show toxic stress in the treated animals especially on blood and blood-forming organs.     

The Tissue-Disposition of Gentamicin in Rats

Abstract: The tissue disposition of ¹⁴C-gentamicin was studied in young rats after a single-dose administration by autoradiographic techniques. The autoradiograms showed a high accumulation of the substance in non-parenchymateous tissues such as cartilages and connective tissues and a strong uptake in the kidney cortex. The in vivo bound substance was displaced from the cartilage at incubations in cation-containing solutions, indicating an ionic binding of the polycationic gentamicin to negatively charged groups in the cartilage (probably carboxyl and sulphate groups of chondroitin sulphate). In the inner ear a localization of the substance was found in the membraneous walls of the chochlea and, at short survival intervals, in the perilymph, whereas the radioactivity in the endolymph was low. Studies in vitro showed an ionic binding of gentamicin to cartilage and in addition to several other tissues, such as the lymphomyeloid system, the gastrointestinal mucosa, the exocrine pancreas, salivary glands, and most prominent, the pigmented tissues. A strong in vitro binding of gentamicin to pigment from beef eyes was also shown. The potential binding sites in the latter tissues are localized intracellularly and are therefore apparently unattainable for the charged hydrophilic gentamicin molecule in vivo.     

Tissue Distribution of Sex Steroids: Concentration of 17β-Oestradiol and Cyproterone Acetate in Selected Organs of Female Wistar Rats

Abstract: The tissue distribution of 17β-oeslradiol and cyproterone acetate was investigated after intravenous and intragastric administration to female Wistar rats by measuring the time course of the concentration of the sex steroids in plasma, liver, kidney, brain, and heart by radioimmunoassay. Test substances were administered intravenously in doses of 0.1 mg/kg each and intragastrically in doses of 10 mg/kg (17β-oestradiol) and 0.1 mg/kg (cyproterone acetate) corresponding to the expected oral bioavailability. Tissue distribution was assessed within each mode of administration by AUC_organ/ AUC_plasma-quotients (Q-values), and between both routes of administration by F-values representing (bio- and organ availability) and R-values, which express the organ load after intragastric compared to intravenous administration if the same amount of drug has been made bioavailable in the plasma after both routes (for explanation see next page). The absolute bioavailability of 17β-oestradiol after intragastric administration of 10 mg/kg was ca. 8%. The oestradiol liver load after intragastric administration was about 20 times higher than after intravenous administration, whereas the drug load of other organs was independent of the administration route. Cyproterone acetate was completely bioavailable after intragastric administration in a dose of 0.1 mg/kg. Cyproterone acetate levels and AUC-values in all organs investigated were higher when compared to the plasma with highest levels in the liver. The organ distribution of cyproterone acetate including the drug liver load was independent of the route of administration.     

Concentration of Metallothionein in Major Organs of Rats after Administration of Various Metals

Concentration of Metallothionein in Major Organs of Rats afterAdministration of Various Metals. WAALKES, M. P., AND KLAASSEN,C. D. (1985) Fundam. Appl. Toxicol. 5, 473–477. The effectof various metals (Cd, Cr, Fe, Pb, Mn, Hg, Ni, Zn) at maximumtolerated doses on metallothionein (MT) concentrations in majororgans (brain, heart, intestine, kidney, liver, lung, pancreas,spleen, stomach, and testes) of rats was measured by the Cd-radioassaytechnique. Zn produced the most dramatic changes in MT, increasingconcentrations 260-, 86-, 44-, and 14-fold over control forpancreas, intestine, liver, and kidney, respectively. Zn increasedMT in every organ examined except brain. Cd was also effectivein increasing MT levels, elevating concentrations in all organsexcept brain and testes. Testes was the only organ in whicha metal decreased MT levels, where Cd produced a 90% decrease.Cr, Fe, Pb, and Mn increased MT concentrations only in hepatictissue, while Hg and Ni increased MT in liver, kidney, and pancreas.Results indicate that Zn is the most effective inducer of MTsynthesis in several tissues and that liver appears to be themost responsive organ to increased MT synthesis following exposureto a number of metals     

内毒素诱导新生大鼠肾脏cAMP、cGMP 及其超微结构的改变

目的 :探讨新生大鼠内毒素 (LPS)血症时肾脏损害的发生机制及地塞米松 (Dex)对其的影响。方法 :7日龄新生大鼠 180只随机分为 3组。A组 :注入 0 .1mL生理盐水 ;B组 :腹腔注射LPS 5mg kg ;C组 :LPS 5mg kg Dex 10mg kg 3组注入液体体积相等。放免法测定肾脏cAMP及cGMP浓度 ,透射电镜观察肾脏超微结构。观察 0 ,2 ,4 ,6 ,2 4h各指标变化。结果 :(1)B组 :肾组织cAMP和cGMP自 2h起高于A组 (P <0 .0 5～P <0 .0 1) ;(2 )C组 :cAMP浓度自2h起高于A、B 2组 (均P <0 .0 1) ,cGMP于 2h显著高于A、B 2组 (P <0 .0 1) ,逐渐下降至 2 4h显著低于B组 (P <0 .0 1)。 (3)肾脏形态变化 :B组 6h后表现为肾小球GBM断裂、上皮细胞足突融合 ,肾小管上皮细胞线粒体空泡变性 ;C组肾损伤明显减轻。结论 :LPS诱导新生大鼠内毒素血症后 ,其肾脏cAMP、cGMP浓度均显著升高 ,肾脏损伤明显 ,Dex通过调节肾脏第二信使信号系统 ,减轻肾损伤 ,对肾脏起一定的保护作用。     

Biochemical Changes after Short-term Oral Exposure of Jatropha curcas Seeds in Wistar Rats

Jatropha curcas (Euphorbiaceae) is a multipurpose shrub with varied medicinal uses and is of significant economic importance. In addition to being the source of biodiesel, its seeds are also considered highly nutritious and could be exploited as a rich and economical protein supplement in animal feeds. However, the inherent phytotoxins present in the seed is the hindrance. The toxicity nature of the seeds of the local variety of J. curcas is not known. Therefore, investigations were undertaken to evaluate the short-term oral toxicity of the seeds of locally grown J. curcas. Short-term toxicity was conducted in rats by daily feeding the basal diet (Group I), and the diet in which the crude protein requirement was supplemented at 25% (Group II) and 50% (Group III) levels through Jatropha seed powder. The adverse effects of Jatropha seed protein supplementation (JSPS) were evaluated by observing alterations in biochemical profiles. The biochemical profile of rats fed on diet with JSPS at both the levels revealed significant reduction in plasma glucose and total protein and increase in plasma creatinine, transaminases (Plasma glutamic pyruvic transaminase and Plasma glutamic oxaloacetic transaminase), and alkaline phosphatase.     

去势雌性大鼠主动脉平滑肌细胞雌激素受体的变化

目的：探讨绝经后血管平滑肌细胞雌激素受体的变化。方法：采用切除双侧卵巢、高脂饲料喂养造模大鼠，观察去势雌性大鼠血脂的变化，并应用免疫组化法(SP法)测定主动脉平滑肌细胞雌激素受体变化。结果：去势雌性大鼠血脂代谢紊乱，主动脉平滑肌细胞雌激素受体水平下降。结论：绝经后女性心血管疾病发病率与雌激素受体水平下降有关。     

Relationships Between Histological and Functional Indices of Acute Chemically Induced Nephrotoxicity

Relationships Between Histological and Functional Indices ofAcute Chemically Induced Nephrotoxicity. Miyajima, H., Hewitt,W.R., Côté, M.G., and Plaa, G.L. (1983). Fundam.Appl. Toxicol. 3: 543–551. Acute renal injury was producedin rats with K₂Cr₂O₇ (5–40 mg/kg, sc) HgCl₂ (0.5–5.0mg/kg, sc) or cephaloridine (0.5–3.0 g/kg, sc). Histological(percentage of normal, degenerated or necrotic cells) and functionalindices (relative kidney weight, renal cortical slice accumulationof organic ions, and blood urea nitrogen content) were evaluated48 hours later. The relative sensitivity of each of these indiceswas determined for each nephrotoxicant. Renal cortical accumulationof organic ions appeared to be the most sensitive of the functionalparameters. A quantitative histological evaluation was foundto be as sensitive an indicator of nephrotoxicity as organicion accumulation. Alterations in each of the functional indiceswere significantly correlated with changes in renal histology.     

实验性汞中毒时肾组织和尿中碱性磷酸酶活性的变化

本研究采用亚急性汞中毒肾损害的大鼠模型,探讨了汞中毒时血、肾和尿中碱性磷酸酶(ALP)活性的变化关系。结果表明,大鼠肾匀浆中 ALP活性明显低于对照组,尿 ALP活性则显著增加。ALP 活性降低的部位在肾近曲小管。体外实验未发现氯化汞对肾、尿ALP 具有直接抑制作用或激活作用。尿中ALP 活性的增高是汞引起的肾小管上皮细胞损伤所致。它可作为汞中毒肾损害的一个观察指标。     

Nephrotoxicities of Aluminium and/or Cadmium-Metallothionein in Rats: Creatinine Excretion and Metabolism of Selected Essential Metals

Abstract: The effects of exposure to aluminium (Al) and cadmium (Cd) on urinary creatinine and protein excretion, and the concentrations of calcium, magnesium and copper in kidney and urine were studied in 32 male adult Wistar rats. The animals were divided into 8 groups, groups 1–4 given a calcium-deficient diet (0.01%, i.e. 0.01 g calcium/100 g diet weight) and groups 5–8 a calcium-adequate diet (0.9%) for 6 weeks. Single daily intraperitoneal injections of AlCl₃ (10.8 mg Al/kg body weight, per day) were done on 6 consecutive days to groups 3, 4, 7 and 8 during the last week of the experiment. One single intraperitoneal injection of cadmium-metallothionein (Cd-MT, 0.4 mg Cd/kg) was administered 12 hr before the final Al dose to groups 2, 4, 6, and 8 and the rats were sacrificed 47 hr after the Cd-MT injection. The rate of creatinine clearance was significantly lower in rats injected intraperitoneally with either Cd-MT or Al, and the concentrations of magnesium and calcium in urine were lower in rats administered both Al and Cd-MT as compared to those in control groups. Histological examination showed that Al was toxic to the kidney tubule cells of rats, however, an adequate supply of calcium in food protected to some extent the renal tubules from Al toxicity as indicated by a higher creatinine clearance, and there was also less tubule damage as shown by histological examination. The copper concentrations in kidney tissue were lower in groups treated with either Al or Cd-MT. The above results indicate that: (1) Al administered by intraperitoneal injection is nephrotoxic in rats; (2) food deficient in calcium increases the vulnerability of the kidney to Al-induced toxicity; (3) the decreased creatinine clearance in Cd-MT-injected rats may explain the low calcium excretion in urine observed in these rats.     

老年高血压患者尿微量蛋白等指标变化研究

目的：研究老年高血压患者尿微量蛋白、内皮素（ET）、C反应蛋白（CRP）的水平变化,为观察早期老年高血压患者靶器官损害探索道路。方法：将130例老年原发性高血压患者根据血压水平分为3组,40例血压正常者为对照组,所有研究对象入选时血尿素氮、肌酐和24h尿蛋白总量均在正常范围内。取晨尿用免疫散射法测定尿白蛋白（Alb）、α1-微球蛋白（α1-MG）、β2微球蛋白（β2-MG）,空腹血测定ET、CRP。结果：随着血压升高,各项尿微量蛋白指标及ET、CRP均有增高趋势。结论：尿微量蛋白、ET、CRP均可作为高血压靶器官损害的监测指标,其中内皮素在高血压的早期靶器官损害中更有检测意义。结论：有必要对基层医院及非药学的医务人员进行长期的ADR专业知识的宣传和培训,以提高医务人员对ADR知识的整体认知水平。     

Effect of Herbal Preparation on Heavy Metal (Cadmium) Induced Antioxidant System in Female Wistar Rats

Cadmium is one of the elements found to damage antioxidant systems in mammals. To ameliorate cadmium toxicity and to prevent oxidative stress, natural products may be useful. In Indian ethnobotanical practice, a mixture of 17 herbal products is used to fortify the reproductive system of women after parturition and to reverse ovarian oxidative stress. Oral administration of this extract to rats exposed to cadmium was useful in reversing oxidative stress. Two different doses of cadmium (50 ppm and 200 ppm) were given to Wistar rats aged 45 and 65 days. An herbal extract derived from 17 plants was administered orally every day at a dose level of 200 mg/kg of body weight to the rats exposed to cadmium. A battery of enzymes involved in antioxidant activity in the ovary, including superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione-s-transferase (GST) were measured in the control, cadmium-exposed rats without treatment and in the cadmium-exposed rats treated with herbal extract. The reduction in SOD, catalase, GPx and GST activity after cadmium exposure improved significantly in the rats treated with the herbal extract (p?相似文献   

Nephrotoxicity of Intravenously Injected Cadmium-Metallothionein: Critical Concentration and Tolerance

Nephrotoxicity of Intravenously Injected Cadmium-Metallothionein:Critical Concentration and Tolerance. MAITANI, T., CUPPAGE,F. E. AND KLAASSEN, C. D. (1988). Fundam. Appl Toxicol. 10,98-108. The nephrotoxicity of Cd-metallothionein (Cd-MT) wasexamined after iv administration of various dosages to mice.The lowest dosage of Cd-MT that produced renal injury was 0.2mg Cd/kg. This dosage of Cd-MT resulted in 10 µ Cd/g inthe kidneys 24 hr after administration. A time-course experimentutilizing a higher (0.3 mg Cd/kg) nephrotoxic dose of Cd-MTdemonstrated that the renal Cd concentration at 4 and 12 hrwas much higher than the critical concentration, but thereafterdecreased to about 10 Mg Cd/g wet tissue by 24 hr. Thus, Cdin excess of 10 Mg/g appears to damage the kidney and then distributesto other tissues and/or is excreted into urine. When a totalof 0.3, 0.4, and 0.8 mg of Cd/kg as Cd-MT was administered individed dosages over 4 days, as much as 30 Mg Cd/g was detectedin the kidney but no renal injury was observed. Thus, the criticalconcentration for producing renal injury after acute administrationof Cd-MT is estimated to be approximately 10 Mg Cd/g wet weight.However, with repeated exposure to Cd-MT, this acute criticalconcentration can be exceeded without producing renal injury,as tolerance to the nephrotoxic effects of Cd-MT develops.     

姜黄素对大鼠环孢素肾毒性的防治作用

目的:观察姜黄素对环孢素肾毒性的防治作用。方法:以30 mg·kg~(-1)·d~(-1)的环孢素灌胃28 d,以姜黄素治疗和预防环孢素所致大鼠肾毒性损伤,观察体重,尿量,血尿素氮和血肌酐的变化,光镜观察肾脏病变以及测定肾脏血红素加氧酶(HO- 1)和碱性成纤维细胞因子(bFGF)的mRNA和蛋白质的表达含量。结果:与正常组相比,使用环孢素的大鼠体重降低(P<0.05),尿量,血尿素氮,肌酐均上升(P<0.05);肾脏损伤性病变较典型;HO-1表达少而bFGF表达多(P<0.01)。姜黄素治疗后使其肾毒性大鼠的体重回升(P<0.05),尿量,血尿素氮和肌酐均回降(P<0.05);病理改变显著好转;HO-1表达回升而bFGF回降(P<0.01);且预防组疗效优于治疗组。结论:姜黄素可防治CsA环孢素所导致的肾毒性损伤,预防效果优于治疗效果。其机制与HO-1和bFGF的表达有关。     

庆大霉素唾液药物浓度测定及临床意义

目的:探求唾液药物浓度与血药浓度的相关性及临床意义。方法:采用放射免疫法测定15例志愿受试者庆大霉素的唾液药物浓度和血药浓度。结果:血液、唾液中的庆大霉素浓度均在用药后1h达峰。结论:血液、唾液中的庆大霉素浓度呈正相关关系,即在庆大霉素治疗药物监测中唾液有可能代替血液。