Taurine and cholestasis associated to TPN. Experimental study in rabbit model

Taurine seems to be essential in the newborn for bile acid (BA) tauroconjugation, and its deficiency has been implicated in total parenteral nutrition-associated cholestasis (TPN-AC). Our purpose was to study the relationship between taurine (Ta) and TPN-AC in rabbits, which have a similar biliary metabolism to that of humans. We used 40 young rabbits, fed for 10 days according to the following four groups: GA [10] given TPN, with amino acid solution (AA) but without taurine (Ta) or its AA-precursors (methionine, cysteine, and serine); GB [10] the same but only without taurine; GC [10] the same but with taurine and its precursors; and GD [10] the control group with oral nutrition and saline infusion. Complete blood and bile analytical data were obtained and analyzed, including plasma AA and BA. Liver samples were studied under optical and electron microscopy. Serum: In GC there was a 20% increase in the AA-precursors, but paradoxically it was greater in GA. Bile: In GC there was 30% more excretion of total and free BA compared with less than 20% in GA and GB. Regarding toxic BA, there was a 15% decline in GLC3S excretion, but more than 20% in LCA excretion, than in GA and GB. Moreover, in GC the glyco-/tauro-conjugate ratio was worse than in the other groups. Histomorphology: While in GA and GB liver steatosis was diffuse (microsteatohepatitis type), in GC there was macrosteatosis with mitochondria-surrounded lipid droplets. In GA and GB, the canaliculi appeared dilated, with abundant bile plugs and loss of microvilli. There are signs that taurine may protect against TPN-AC. The mechanism does not seem to be BA tauroconjugation, but probably taurine’s antioxidant, membrane stabilization (with Ca2+ and HCO3-), and/or osmotic effects.     

Taurine-induced modulation of voltage-sensitive Na+ channels in rat dorsal root ganglion neurons

The physiological role of taurine, an abundant free amino acid in the neural system, is still poorly understood. The aim of this study was to investigate its effect on TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) Na+ currents in enzymatically dissociated neurons from rat dorsal root ganglion (DRG) with conventional whole-cell recording manner under voltage-clamp conditions. A TTX-S Na+ current was recorded preferentially from large DRG neurons and a TTX-R Na+ current preferentially from small ones. For TTX-S Na+ channel, taurine of the concentration > or = 10 mM shifted the activation curve in the depolarizing direction and the inactivation curve in the hyperpolarizing direction. There was no change in the activation curve for TTX-R Na+ channel and the inactivation curve was shifted in the hyperpolarizing direction slightly in the presence of taurine > or = 20 mM. When the recovery kinetics was examined, the presence of taurine resulted in a slower recovery from inactivation of TTX-S currents and no change of TTX-R ones. All the effects of taurine were weakly concentration-dependent and partly recovered quite slowly after washout. Our data indicate that taurine alters the properties of Na+ currents in intact DRG neurons. These may contribute to the understanding of taurine as a natural neuroprotectant and the potential of taurine as a useful medicine for the treatment of sensory neuropathies.     

Effects of betaine supplementation on hepatic metabolism of sulfur-containing amino acids in mice

BACKGROUND/AIMS: We previously reported that acute betaine treatment induced significant changes in the hepatic glutathione and cysteine levels in mice and rats. The present study was aimed to determine the effects of dietary betaine on the metabolism of sulfur-containing amino acids. METHODS/RESULTS: Male mice were supplemented with betaine (1%) in drinking water for up to 3 weeks. Changes in hepatic levels of major sulfur amino acid metabolites and products were stabilized after 2 weeks of betaine supplementation. Betaine intake increased methionine, S-adenosylmethionine, and S-adenosylhomocysteine levels significantly, but homocysteine and cystathionine were reduced. Methionine adenosyltransferase activity was elevated to three-fold of control. Cysteine catabolism to taurine was inhibited as evidenced by a decrease in cysteine dioxygenase activity and taurine levels in liver and plasma. Despite the significant changes in the transsulfuration reactions, neither hepatic cysteine nor glutathione was altered. Betaine supplementation decreased the hepatotoxicity induced by chloroform (0.5 ml/kg, ip) significantly. CONCLUSIONS: Betaine supplementation enhances recycling of homocysteine for the generation of methionine and S-adenosylmethionine while reducing its utilization for the synthesis of cystathionine and cysteine. However, the hepatic levels of cysteine or glutathione are not affected, most probably due to the depression of taurine generation from cysteine.     

牛磺酸抑制肾性高血压大鼠心肌细胞凋亡的研究

目的:探讨牛磺酸对肾性高血压大鼠左室心肌细胞凋亡的影响。方法:75只大鼠随机分为3组,模型组、假手术组和给药组。其中模型组:采用二肾一夹(2KIC)法建立肾血管性高血压大鼠模型;给药组:高血压模型成功后,于术后4周末开始灌饲牛磺酸50mg/(kg·d)8周。采用末端脱氧核昔酸转移酶介导的dUTP缺口末端标记法(TUNEL)进行心肌细胞凋亡原位检测;放射免疫法检测心肌AngⅡ含量;分光光度计法检测心肌细胞DNA含量。结果:进入结果分析的模型组、假手术组及用药组分别为17、30和8只。与假手术组相比,模型组术后第4、12周末心肌细胞凋亡均明显增多(P<0.01);心肌细胞DNA含量和AngⅡ含量亦明显增多(P<0.01)。与4周末模型组相比,12周末模型组血压心肌细胞凋亡增多(P<0.05),心肌DNA含量明显增多(P<0.01),AngⅡ含量增多(P<0.01)。与12周末模型组相比,给药组心肌细胞凋亡减少(P<0.01),心肌DNA和AngⅡ含量明显减少(P<0.01)。结论:肾性高血压大鼠心肌细胞凋亡增多,牛磺酸治疗可抑制心肌细胞凋亡。     

Amino acid signatures in the developing mouse retina

This study characterizes the developmental patterns of seven key amino acids: glutamate, γ-amino-butyric acid (GABA), glycine, glutamine, aspartate, alanine and taurine in the mouse retina. We analyze amino acids in specific bipolar, amacrine and ganglion cell sub-populations (i.e. GABAergic vs. glycinergic amacrine cells) and anatomically distinct regions of photoreceptors and Müller cells (i.e. cell bodies vs. endfeet) by extracting data from previously described pattern recognition analysis. Pattern recognition statistically classifies all cells in the retina based on their neurochemical profile and surpasses the previous limitations of anatomical and morphological identification of cells in the immature retina. We found that the GABA and glycine cellular content reached adult-like levels in most neurons before glutamate. The metabolic amino acids glutamine, aspartate and alanine also reached maturity in most retinal cells before eye opening. When the overall amino acid profiles were considered for each cell group, ganglion cells and GABAergic amacrine cells matured first, followed by glycinergic amacrine cells and finally bipolar cells. Photoreceptor cell bodies reached adult-like amino acid profiles at P7 whilst Müller cells acquired typical amino acid profiles in their cell bodies at P7 and in their endfeet by P14. We further compared the amino acid profiles of the C57Bl/6J mouse with the transgenic X-inactivation mouse carrying the lacZ gene on the X chromosome and validated this animal model for the study of normal retinal development. This study provides valuable insight into normal retinal neurochemical maturation and metabolism and benchmark amino acid values for comparison with retinal disease, particularly those which occur during development.     

牛磺酸对神经干细胞因子表达的影响

目的观察牛磺酸是否影响神经干细胞因子mRNA的表达。方法选择成年雄性SD大鼠63只,使用线栓法建立大脑中动脉缺血再灌注模型（MCAO）。随机分为治疗组（自造模当日开始,静脉注射80mg／kg牛磺酸,持续10min,每日1次,连用7d）和对照组（静脉注射0．9％氯化钠注射液1训,其余相同）,每纽再随机分为再灌流2h、24h、3d、7d、14d组（n=6）,假手术组（n=3）。原位杂交检测脑缺血再灌注后脑组织干细胞因子（stem cell factor,SCF）mRNA的表达。结果假手术组SCFmRNA在皮质、纹状体和室旁区有微弱的表达。对照组缺血侧SCFmRNA的表达,皮质除2h以外、纹状体除2h以外、室旁区除2h、14d以外各时间点均明显高于假手术组（t=2．16—25．19,P〈0．05）。治疗组SCFmRNA表达较对照组在皮质、纹状体及室旁区均显著升高（t：5．19～26．17,P〈0．05）。结论牛磺酸可以促进大鼠局灶性脑缺血再灌注后SCFmRNA的表达。     

Roles of neurotransmitter amino acids in seizure severity and experience in the genetically epilepsy-prone rat

This investigation was designed to compare seizure-naive and seizure-experienced genetically epilepsy-prone rats (GEPRs) in order to distinguish transmitter amino acid changes related to seizure severity from those associated with seizure experience. Moderate (GEPR-3) and severe (GEPR-9) seizure male GEPRs were divided into seizure-naive and seizure-experienced groups based on whether seizure-inducing acoustical stimuli had been presented between 45 and 60 days of age, and then were sacrificed at76 ± 3 days. γ-Aminobutyric acid (GABA) concentrations were lower in both GEPR-3s and GEPR-9s compared to non-epileptic controls in each brain region examined. Aspartate content was elevated in 5 of 6 brain areas in GEPR-9s compared to non-epileptic controls, and in 3 regions was higher in GEPR-9s than in GEPR-3s. In contrast, taurine concentrations were higher in GEPR-3s than in non-epileptic controls in each region, and in 4 areas were higher in GEPR-3s than in GEPR-9s. Changes resulting from seizure experience consisted of increases in aspartate, glutamate and glycine in seizure-experienced compared to seizure-naive groups in inferior colliculus and in motor-sensory and frontal cortices. These findings suggest that the high levels of taurine in GEPR-3s and the elevated content of aspartate in GEPR-9s have roles as determinants of seizure severity. The low concentrations of GABA in both types of GEPRs are consistent with a role for this amino acid in determination of seizure susceptibility. Furthermore, the seizure-induced changes in aspartate and glutamate in both types of GEPRs support the concept that these excitatory amino acids mediate changes in seizure predisposition. The current results are in agreement with previous studies indicating that imbalances in neurotransmitter amino acids are important factors in determinig seizure behavior in the GEPR.     

牛磺酸对放射小鼠生物学效应的影响

目的 :研究牛磺酸对受照射小鼠的生物学效应。方法 :采取腹腔注射药物 ,6 0 Co -γ射线全身一次性照射。结果 :牛磺酸浓度为 2 40mg/kg时 ,能显著提高受照射小鼠的存活率 ,并有增加白细胞数量和降低微核率的功能。结论 :牛磺酸对受照射小鼠有一定的辐射防护作用     

药物牛磺酸镁合成工艺的研究

目的:合成牛磺酸和镁的盐或配合物作为新型的药物从而达到更好的治疗效果.方法:分别用MgCl2、MgSO4、Mg(AC)2与牛磺酸在不同条件下反应,筛选出较为理想的方法后用正交设计法对其反应条件进行优化.结果:以MgCl2为原料牛磺酸镁产量最高;通过正交设计实验得出优化条件为反应温度100℃,反应时间7 h,牛磺酸与MgCl2物质的量之比2:1,牛磺酸浓度5%.结论:在适当的条件下 MgCl2、MgSO4、Mg(AC)2都可以与牛磺酸发生反应,生成牛磺酸镁;从产量角度分析以MgCl2为原料最为理想.     

牛磺酸防护高能冲击波致肾损伤的实验研究

目的 探讨牛磺酸对高能冲击波(HESW)致家兔肾损伤的防护作用及机制.方法20只雄性新西兰成年家兔随机分2组,每组10只,均予12.75 kV冲击波冲击左肾下极1500次.实验组在冲击的同时静脉滴注牛磺酸150 mg/kg,对照组给予等容积的生理盐水,在冲击前及冲击后3 d测定血丙二醛(MDA)、超氧化物歧化酶(SOD)的变化,检测肾脏组织学变化及热休克蛋白70(HSP70)的表达.结果 冲击前实验组和对照组血MDA分别为(2.2±0.4)、(2.1±0.4)mmol/L,SOD分别为(56.4±9.9)、(55.8±10.1)μU/L,差异均无统计学意义(P＞0.05).冲击后实验组血MDA、SOD分别为(2.7±0.7)mmol/L、(55.3±5.7)μU/L,与冲击前相比,差异无统计学意义(P＞0.05);对照组血MDA、SOD分别为(5.7±0.7)mmol/L、(33.3±3.5)μU/L,与冲击前相比,差异有统计学意义(P＜0.05).冲击后实验组和对照组肾小管评分分别为7.2±0.8和31.8±1.9,HSP70分别为25.2±4.1和6.4±0.9,差异均有统计学意义(P＜0.05).结论 牛磺酸对HESW致兔肾损伤有良好的防护作用,防护机制可能与其抗氧化作用和诱导HSP70合成增多有关.