The long-term effect of dietary administration of refined sugars and sugar alcohols on plasma biochemistry, urine biochemistry and tissue histology in mice given a limited degree of dietary self-selection

A prototype animal feeding model is described in which mice were meal-fed a balanced diet but were given free access to water (controls) or 20% (w/v) solutions of glucose, sucrose, fructose, xylitol or sorbitol. Under these conditions it was found that the provision of an alternative energy source, in the form of a refined carbohydrate, produced marked effects on total energy intake, mouse cube (i.e. balanced energy) intake and body weight. There were also changes in the metabolic states of the animals as assessed by serum levels of glucose, urea and cholesterol, plasma levels of lactate and D-3-hydroxybutyrate, and urinary excretion of urea and oxalate. Histological examinations of tissue indicated that the sucrose-fed mice had a tendency to suffer from acute congestion of the lungs and liver steatosis. Given a limited degree of dietary self-selection it appears that mice are more likely to be at risk of excessive food consumption and obesity when given glucose- or sucrose-containing diets than they are when fructose-, xylitol- or sorbitol-containing diets are given.     

注射用丹参(冻干)中糖和糖醇类成分的定性定量分析

目的:研究建立注射用丹参(冻干)中糖和糖醇成分定性、定量分析的方法。方法:以l-甲基咪唑作溶剂和催化剂,盐酸羟胺和乙酸酐为肟化和乙酰化试剂,将注射用丹参(冻干)样品中的糖类成分乙酰化后,再利用GC-MS联用技术进行定性和定量分析。结果:对注射用丹参(冻干)中所含8个糖和糖醇成分进行了结构确证,并对其中6个成分的含量进行了测定,6个成分的线性关系良好(r≥0.9995),平均回收率在95.77%～104.4%之间。结论:本法操作简便、灵敏、准确,可用于注射用丹参(冻干)中糖和糖醇成分的质量控制。     

迷迭香酸对大鼠肾草酸钙结石形成的影响

目的:探讨迷迭香酸对大鼠肾草酸钙结石形成的影响。方法:Wistar♂大鼠36只,随机分为6组,每组6只,分别为正常组,模型对照组,不同剂量迷迭香酸组和阳性对照组(肾石通颗粒剂)。采用1%乙二醇+2%氯化铵,每天ig一次诱导大鼠草酸钙结石模型形成,连续28d,各组同步给药或纯化水。检测各组大鼠成石不同时期的尿液肌酐(Cr)、尿酸(UA)水平,草酸(OX)、枸橼酸(Cit)和Ca2+含量。造模28d结束后,检测血生化及肾草酸(OX)、枸橼酸(Cit)和Ca2+含量,测定肾指数,采用HE和Von-Kossa’s染色,观察肾组织病理变化及草酸钙结晶发生与形态。结果:迷迭香酸中剂量(0.05g.kg-1)、高剂量(0.1g.kg-1)组大鼠24h尿Cr、UA的水平及尿OX、Ca2+的排泄量,血清Cr、BUN、UA,肾组织OX、Ca2+含量,均显著低于模型对照组;肾组织病理变化明显改善,草酸钙的结晶发生明显少于模型对照组,形态分布程度也减轻,而肾指数增加。结论:迷迭香酸可以抑制大鼠草酸钙结石的形成。     

Interaction of methylparaben preservative with selected sugars and sugar alcohols

The interaction of methylparaben preservative with selected sugars (glucose, fructose, sucrose, lactose, maltose, cellobiose) and sugar alcohols (lactitol, maltitol) were demonstrated in this study. It was observed that the formation of transesterification reaction products between methylparaben and the selected sugars occurred only under mild reaction conditions (e.g., pH 7.4 at 50 degrees C ), which were confirmed by HPLC-UV studies and mass spectrometry. On the other hand, under alkaline conditions and high temperature, degradation of the sugars predominated. Because sugars could easily undergo many possible degradation reactions and isomerization including on-column anomerization, the chromatograms of the reaction products were more complicated than those obtained from sugar alcohols. Sucrose, a nonreducing sugar, was much more stable than other selected sugars. The chromatogram of the transesterification reaction products of methylparaben with sucrose clearly showed eight peaks, which were likely to correspond to the same number of hydroxyl groups of sucrose. To compare the rate of the transesterification reaction of methylparaben with sucrose to that with sorbitol, kinetic studies were carried out. Similar rate constants were observed: 5.4 x 10(-7) L mol(-1) s(-1) and 4.9 x 10(-7) L mol(-1) s(-1) for sucrose and sorbitol, respectively.     

The cytotoxicity of oxalate, metabolite of ethylene glycol, is due to calcium oxalate monohydrate formation

Oxalate is a minor, but important metabolite of ethylene glycol and has been directly linked with acute and subchronic renal toxicity in ethylene glycol poisoning. Numerous studies have characterized the cytotoxicity of oxalate as including plasma membrane damage and organelle injury. Oxalate has two forms in vivo: oxalate ions and calcium oxalate monohydrate (COM) crystals that readily form in the presence of calcium. The present study was designed to compare the cytotoxicity of the oxalate ion and COM crystals in human and rat cells. In rat red blood cells, the oxalate ion did not increase hemolysis, while COM crystals produced hemolysis with a concentration-dependent increase. In human proximal tubule (HPT) cells in culture, COM suspensions, at concentrations >3 mM but with no oxalate ion, caused cytotoxicity as evidenced by the release of lactate dehydrogenase (LDH) into media. Cytotoxicity was not observed in HPT cells treated with oxalate solutions that contained no COM because EDTA prevented its formation. The cytotoxic effects of COM to HPT cells were potentiated by acidosis (pH 6.5), but not by glycolate, the major metabolite of ethylene glycol. The toxicity of COM to HPT cells and to proximal tubule cells from Wistar and F-344 rats, compared using both ethidium homodimer uptake and LDH leakage, increased in human and rat cells in a concentration-dependent manner. Rat cells were more sensitive to COM than HPT cells, but there were no apparent differences between the effects in Wistar cells and F-344 cells. These results demonstrate that COM crystals, and not the oxalate ion, are responsible for the membrane damage and cell death observed in normal human and rat PT cells and suggest that COM accumulation in the kidney is responsible for the renal toxicity associated with ethylene glycol exposure.     

Combined effect of dietary calcium and calcium antagonists on blood pressure reduction in spontaneously hypertensive rats.

Calcium supplementation and calcium channel blockers are known to have antihypertensive effects in similar subsets of hypertensive patients, as well as in spontaneously hypertensive rats (SHR). To investigate this apparent paradox, we placed 12-week-old SHR on one of three dietary levels of calcium (0.2, 0.4, or 0.8%), as well as on one of four doses of nifedipine (0, 50, 150, or 300 mg/kg food) for 8 weeks. We performed a similar experiment using four verapamil doses (0, 300, 900, or 1,800 mg/kg food). In the nifedipine experiment, two-way analysis of variance showed significant independent antihypertensive effects of both nifedipine (p less than or equal to 0.0001) and calcium (p less than 0.0001) and significant interaction (p = 0.0034), the latter suggesting a synergistic effect. In the verapamil experiment, both calcium and verapamil again had significant independent antihypertensive effects (p = 0.006 and p = 0.004, respectively), but there was no significant interaction. Although the effects of the calcium supplement or calcium antagonist alone were significant, such hypotensive responses were not optimal or predictable or clearly dose-dependent. However, the combination of a calcium supplement and calcium antagonist resulted in predictable or dose-dependent effects, and the optimal effect was reflected in the reduction of the SHR pressure to normal range for Wistar-Kyoto (WKY) rats. These results appear to indicate that supplementary calcium and calcium channel blockers act by different mechanisms in lowering blood pressure (BP), and that the combination of those differing mechanisms of action may have potential therapeutic benefit.     

尿石汤配方颗粒改善肾草酸钙结石大鼠肾功能效果及其机制

目的:探讨尿石汤配方颗粒改善肾草酸钙结石(CaXO)大鼠肾功能效果及其机制.方法:建立草酸钙肾结石大鼠模型,检测大鼠造模前后体质量变化,肾脏质量、脏器系数变化,排尿量、尿液pH、尿液Ca2+、尿液结晶数量及类型,观察肾结石模型在大鼠机体上的宏观变化.采用He染色和Von-Kossa'S染色,观察尿石汤配方颗粒对肾结石模...     

Oral Reference Dose for ethylene glycol based on oxalate crystal-induced renal tubule degeneration as the critical effect

Several risk assessments have been conducted for ethylene glycol (EG). These assessments identified the kidney as the primary target organ for chronic effects. None of these assessments have incorporated the robust database of species-specific toxicokinetic and toxicodynamic studies with EG and its metabolites in defining uncertainty factors used in reference value derivation. Pertinent in vitro and in vivo studies related to one of these metabolites, calcium oxalate, and its role in crystal-induced nephropathy are summarized, and the weight of evidence to establish the mode of action for renal toxicity is reviewed. Previous risk assessments were based on chronic rat studies using a strain of rat that was later determined to be less sensitive to the toxic effects of EG. A recently published 12-month rat study using the more sensitive strain (Wistar) was selected to determine the point of departure for a new risk assessment. This approach incorporated toxicokinetic and toxicodynamic data and used Benchmark Dose methods to calculate a Human Equivalent Dose. Uncertainty factors were chosen, depending on the quality of the studies available, the extent of the database, and scientific judgment. The Reference Dose for long-term repeat oral exposure to EG was determined to be 15 mg/kg bw/d.     

模拟加速度对肾草酸钙结石模型大鼠氧化应激的影响

目的 探讨加速度暴露对肾草酸钙结石模型大鼠氧化应激的影响.方法 采用乙二醇饮水和氯化铵灌胃法诱导建立大鼠草酸钙结石模型,将40只8周龄Wistar健康雄性大鼠随机分为4组(每组10只):空白对照组(A组)、单纯诱石组(B组)、加速度并诱石组(C组)和单纯加速度组(D组).其中A组采用自来水饮水+生理盐水2 mL/d灌胃,B组采用1％乙二醇+2％氯化铵溶液2 mL/d灌胃,C组在B组的基础上给予加速度(+6G)暴露,D组单纯给予+6G暴露.各组大鼠在相同条件下饲养28 d后收集血液及双肾标本,左肾组织做石蜡切片HE染色,光镜下观察草酸钙结晶情况;右肾组织制成组织匀浆,测定血液和右肾组织匀浆中丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、还原性谷胱甘肽(GSH)和谷胱甘肽过氧化物酶(GSH-Px)含量,以了解氧化应激情况.结果 单纯诱石组和加速度并诱石组肾组织草酸钙结晶评分较空白对照组和单纯加速度组均显著增高(P＜0.01),加速度并诱石组结晶评分亦较单纯诱石组增高(P＜0.01).单纯诱石组和加速度并诱石组与空白对照组比较,大鼠血、肾组织MDA浓度显著升高(P＜0.01),血、肾组织SOD、CAT、GSH-Px浓度显著降低(p＜0.01).结论 加速度暴露可能是泌尿系结石形成的危险因素之一,其机制可能与加速度暴露引起大鼠肾脏组织氧化应激损伤有关.     

钙拮抗剂对在体大鼠血糖和血清胰岛素水平的影响

作者观察了钙拮抗剂一异搏定对在体大鼠血糖和血清胰岛素水平的影响,结果表明,异搏定能升高大鼠基础血糖和基础胰岛素水平。另外,在大鼠糖耐量试验中,异搏定能使大鼠对葡萄糖诱导的胰岛素反应降低和延迟,从而导致大鼠的糖耐量降低和糖耐量高峰的后移。     

柠檬乌梅提取液预防肾草酸钙结石作用机制的研究

目的:本文旨在通过研究柠檬乌梅提取液对预防肾草酸钙结石产生的协同效应及其作用机制,为进一步研究和临床预防和治疗肾结石的应用提供理论基础。方法:将50只大鼠（体质量200～250 g）按随机数字表法分为5组,A组（对照组）、B组（成石组）、C组（柠檬提取液组）、D组（乌梅提取液组）、E组（柠檬乌梅提取液组）,造模和加药处...     

原钒酸钠对小肠糖吸收的影响

目的　观察原钒酸钠对葡萄糖及麦芽糖吸收的影响 ,并初步探讨其影响糖吸收的机制。方法　①正常Wistar大鼠分为正常对照组、生理盐水对照组、阿卡波糖组 (30mg·kg-1)、原钒酸钠大剂量 (16mg·kg-1)、中剂量 (4mg·kg-1)和小剂量 (1mg·kg-1)组 ,分别灌胃葡萄糖和麦芽糖后 ,用氧化酶法测空腹血糖值及糖耐量。②从小肠上段提取α 葡萄糖苷酶 ,检测原钒酸钠对酶的抑制作用。结果　①原钒酸钠可延迟灌胃葡萄糖 (2 2g·kg-1)引起的血糖升高且 3个剂量组血糖曲线下面积 (AUC)均低于对照组 ,分别为 (8 2 4±0 6 3)mmol·h-1·L-1(P <0 0 1) ,(9 6 9± 0 38)mmol·h-1·L-1(P <0 0 1) ,(13 76± 0 39)mmol·h-1·L-1(P <0 0 5 ) ;②原钒酸钠和阳性对照组均可延缓灌胃麦芽糖 (2 2g·kg-1)引起的血糖升高 ,且大、中剂量可抑制血糖峰值升高 (P <0 0 5 ) ,各给药组AUC均低于对照组 ,大剂量和中剂量为(8 97± 1 5 6 )和 (6 19± 0 4 7)mmol·h-1·L-1均低于阳性对照组 (13 10± 0 4 3)mmol·h-1·L-1(P <0 0 5 ) ;③原钒酸钠 1、10、10 0 μmol·L-1均可抑制正常大鼠小肠α 葡萄糖苷酶的活性 ,其抑制百分率分别为 5 9 76 %、6 8 18%、87 2 2 % ,且大剂量和中剂量均大于阳性对照组的 6 0 94 % ,分别为P<0     

The effect of ethylene exposure on ethylene oxide in blood and on hepatic cytochrome p450 in Fischer rats.

Ethylene (74-85-1) is an important petrochemical and is produced endogenously. It is metabolized to ethylene oxide (EO) by cytochrome P450. We studied the inhibition of cytochrome P450 activity during exposure to ethylene, and verified that this inhibition was reflected in the concentration of EO in the blood. Male F344 rats were exposed to 1000, 600, and 300 ppm ethylene by nose-only inhalation for up to 6 h. Blood samples were obtained during exposure. On exposure to 600 ppm ethylene, blood EO concentration increased during the first hour of exposure and then decreased to approximately half of the peak blood concentration. A less pronounced decrease was observed at 300 ppm, and at 1000 ppm little change was observed between 10 min and 6 h of exposure. For the analysis of cytochrome P450 and isozyme-specific substrate activities, groups of four male F344 rats were removed for the collection of liver at various times after exposure to 300, 600, or 1000 ppm ethylene. At all concentrations, liver microsomal cytochrome P450 decreased during exposure. Of the various monooxygenase activities measured, 4-nitrophenol hydroxylase was the one most consistently altered, with maximal inhibition (approximately 50%) at 2 h of exposure to 1000 ppm ethylene, 4 h at 600 ppm, and 6 h at 300 ppm. Activity recovered to control levels by 6 h after exposure. Cytochrome P450 2E1 appears to be the major isoform of cytochrome P450 inhibited by exposure to ethylene, and this may explain in part the observed alteration in EO blood kinetics.     

The effect of calcium load and the calcium channel blocker verapamil on gentamicin nephrotoxicity in rats

Gentamicin (GM) is used against serious and life-threatening Gram negative infections. However its use is limited by the occurrence of nephrotoxicity. Reports on the interaction between GM nephrotoxicity and calcium (Ca²⁺) or Ca blockers are conflicting. Therefore, in the present work we assessed the effect of treatment of rats with graded doses of calcium carbonate, CaCO₃ (0.25, 0.5 or 1.0 g/kg) orally, or the Ca²⁺ channel blocker verapamil (1.75, 3.5 or 7.0 mg/ kg) intramuscularly (i.m.), on the nephrotoxicity induced by concomitant i.m. treatment with GM (80 mg /kg/day for 6 days). Nephrotoxicity was evaluated histopathologically by light microscopy and biochemically by measuring the concentrations of urea and creatinine in plasma, reduced glutathione (GSH), lipid peroxidation and superoxide dismutase (SOD) activity in kidney cortex. The results indicated that the administration of CaCO₃ produced a dose-dependent amelioration in the biochemical indices of nephrotoxicity in plasma and renal cortex, which was significant at the two higher doses used. The histological picture of the renal proximal tubules followed a similar pattern. Treatment with verapamil induced a dose-dependent potentiation in the biochemical parameters of nephrotoxicity that was significant only at the highest dose used (7 mg/kg). This dose also exacerbated the GM-induced histological necrosis. The above interactions may be clinically relevant in patients treated concurrently with these agents.     

Protective effect of triterpenes on calcium oxalate crystal-induced peroxidative changes in experimental urolithiasis.

Naturally occurring pentacyclic triterpenes of plant origin have been identified as possessing a wide range of pharmacological effects. Lupeol (Lupa-21,20(29) dien, 3beta-ol) has been found to be efficient in reducing the risk of stone formation in animals by way of preventing crystal-induced tissue damage and dilution of urinary stone-forming constituents. In the present study, two structurally related triterpenes, lupeol and betulin (Lupa-20(29)ene-3,28 diol) were assessed for their antilithiatic effect. Foreign body implantation method followed by supplementation of ammonium oxalate was adapted to induce stone formation in the bladder. This led to elevated lipid peroxidation and depleted antioxidant status in the renal tissues. Both the triterpenes were equally efficient in minimizing crystal-induced renal peroxidative changes measured in terms of malondialdehyde and subsequent tissue damage. The antioxidant status, comprising of the enzymatic and non-enzymatic components, was found to be significantly depleted in the kidney and bladder of stone-forming animals. Both lupeol and betulin were comparable in their ability to restore the thiol status and the antioxidant enzymes like superoxide dismutase, catalase and glutathione peroxidase. The mechanism by which the two compounds render protection against oxalate-induced toxic manifestations and free radical production may involve the inhibition of calcium oxalate crystal aggregation and enhancement of the body defence systems. 2000 Academic Press.     

抗肿瘤抗生素博安霉素对大鼠肾功能及形态学的影响

研究了抗肿瘤抗生素博安霉素（boanmycin）对大鼠肾功能及病理形态学的影响。在急性和亚急性毒性实验中，博安霉素引起大鼠血清尿素氮、血清肌酐、尿蛋白等明显增加，且具有剂量依赖性。大鼠毒性反应后期，肾皮质区细胞广泛变性坏死；超微结构显示近曲小管上皮细胞微绒毛肿胀，线粒体肿大，排列紊乱，细胞核固缩或核溶解。     

白川降压胶囊对肾性高血压大鼠血压的影响

目的　观察白川降压胶囊 (BC)对肾性高血压模型大鼠的急性降压作用和对心率的影响。方法　采用颈动脉插管直接测压法测量血压和心率。结果　给予 BC 0 .1 5 ,0 .3 ,0 .6 g· kg-13 0 ,6 0 ,90 ,1 2 0 min后大鼠收缩压、舒张压均明显降低 ,与对照组比较 P <0 .0 5。 BC各剂量给药后大鼠心率无明显变化 ,与对照组比较 P >0 .0 5。结论　BC对肾性高血压大鼠具有明显的急性降压作用 ,对心率无影响