支链氨基酸对动物实验性肝损伤作用的研究

目的:研究支链氨基酸(Branched Chain Amino Acid,BCAA)对动物实验性肝损伤的保护作用.方法:采用化学毒物D-氨基半乳糖胺盐酸盐(D-Galn)急性肝损伤模型,四氯化碳(CCl4)急性肝损伤模型,观察支链氨基酸对肝损伤动物生化指标和病理组织学改变的影响.结果:1.支链氨基酸高、低剂量组均对小鼠D-Galn肝损伤ALT及AST增高有明显的降低作用(P<0.01、P<0.05),支链氨基酸+乙肝宁联合用药组比单纯用乙肝宁组降酶作用更强(P<0.01).病理组织学检查结果:支链氨基酸对D-Galn引起的肝细胞变性、坏死等病变有明显改善作用,与模型组相比,高剂量组改善56.4%,低剂量组改善52%,乙肝宁+氨基酸混合用药组改善更明显为71.6%.2.支链氨基酸高剂量组对大鼠CCl4肝损伤ALT、AST活性增加及胆红素含量增高有明显的降低作用(P<0.01).病理组织学检查结果:支链氨基酸对CCl4肝损伤引起的肝细胞变性、坏死等病变有明显改善作用,与模型组相比,高剂量组改善27%,乙肝宁+氨基酸混合用药组改善28.2%.结论:支链氨基酸对小鼠D-Galn肝损伤及大鼠CCl4肝损伤具有保护作用.     

支链氨基酸对动物实验性肝损伤作用的研究

目的：研究支链氨基酸（Ｂｒａｎｃｈｅｄ Ｃｈａｉｎ Ａｍｉｎｏ Ａｃｉｄ,ＢＣＢＡＡ）对动物实验性肝损伤的保护作用。方法：采用化学毒物Ｄ－氨基半乳糖胺盐酸盐（Ｄ－Ｇａｌｎ）急性肝损伤模型,四氯化碳（ＣＣｌ４）急性肝损伤模型,观察支链氨基酸对肝损伤动物生化指标和病理组织学改变的影响。结果：１．支链氨基酸高、低剂量组均对小鼠Ｄ－Ｇａｌｎ肝损伤ＡＬＴ及ＡＳＴ增高有明显的降低作用（Ｐ〈０．０１,Ｐ〈０．０５）,支链氨基酸＋乙肝宁联合用药组比单纯用乙肝宁组降酶作用更强（Ｐ〈０．０１）。病理组织学检查结果：支链氨基酸对Ｄ－Ｇａｌｎ引起的肝细胞变性、坏死等病变有明显改善作用,与组相比,高剂量组改善５６．４％,低剂量组改善５２％,乙肝宁＋氨基酸混合用药组改善更明显的降低作用（Ｐ〈０．０１）。病理组织学检查结果：支链氨基酸对ＣＣ     

肝舒胶囊对急性肝损伤动物的保护作用

目的 研究肝舒胶囊对大、小鼠急性肝损伤的保护作用.方法 采用皮下注射四氯化碳(CCl_4)诱导小鼠产生急性肝损伤模型,测定血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸基转移酶(AST)、总胆红素(TBIL)的含量和肝指数;腹腔注射D-氨基半乳糖胺盐酸盐(D-Gal)致大、小鼠急性肝损伤模型,测定血清中ALT、AST、ALP的含量及对肝指数的影响.结果 肝舒胶囊对CCl_4致小鼠急性肝损伤血清中的ALT、AST、TBIL升高有一定的抑制作用,但无统计学差异;肝舒胶囊高、中剂量能显著降低D-Gal致急性肝损伤小鼠血清中ALT、AST、ALP的含量,中剂量(0.95 g·kg~(-1))能显著降低D-Gal致急性肝损伤大鼠血清中ALT、AST的含量.结论 肝舒胶囊对化学性急性肝损伤有一定的保护作用.     

铁甲草急性毒性实验及D-氨基半乳糖性肝损伤小鼠的影响研究

目的 观察铁甲草急性毒性反应;观察铁甲草水煎液作用于肝损伤小鼠后,对ALT、AST水平的影响.方法 铁甲草给予最大剂量,观察药物急性毒性反应;将小鼠随机分为高、低剂量组、阳性对照组、模型对照组和正常对照组,除了正常对照组,各组腹腔注射D-GalN造肝损伤模型后,各组连续给药5天,每天1次,末次给药1h后,取血清测定ALT和AST水平.结果 小鼠最大耐受剂量为150 g/kg,相当于临床用药的500倍,在该剂量下,动物一般状态良好,未见明显毒性反应症状;铁甲草水煎液高剂量组与模型组比较,ALT、AST水平差异有统计学意义,虽然铁甲草低剂量组与模型组ALT、AST值在统计学上没有显著性差异,但有减低的趋势.结论 小鼠最大耐受剂量下,没有明显急性毒性作用;铁甲草水煎液能降低肝损伤小鼠ALT、AST水平,提示铁甲草水煎液对肝损伤具有一定的保护作用,高剂量组作用明显优于低剂量组,说明了保护作用与剂量有关,作用机制有待于进一步深入探讨和研究.     

降酶灵胶囊对急性肝损伤的药效研究

目的观察降酶灵胶囊保肝降酶的作用。方法采用四氯化碳(CCl4)制作小鼠的急性肝损伤模型,然后给予不同剂量降酶灵胶囊,观察小鼠血清谷丙转氨酶(ALT)和肝病理学的变化;用D-氨基半乳糖对大鼠造成急性肝损伤模型,再给予不同剂量降酶灵胶囊,观察大鼠血清ALT和总胆红素(TBIL)的变化。结果降酶灵胶囊0.135、0.270、0.540g/kg组均能明显降低由CCl4引起的小鼠急性肝损伤的ALT;降酶灵胶囊0.135、0.270g/kg组均能显著降低由D-氨基半乳糖所致大鼠急性肝损伤血清ALT与TBIL。结论降酶灵胶囊具有保肝降酶和降低胆红素的作用。     

蒙花苷及其代谢产物对大鼠急性肝损伤的保护作用

目的 研究蒙花苷及其代谢产物(刺槐素、芹菜素、间苯三酚、对羟基苯甲酸和对羟基苯甲醛)对D-氨基半乳糖胺(D-GalN)致大鼠急性肝损伤的保护作用。方法 健康SD大鼠72只,随机分为正常组、模型组、阳性对照组(100 mg·kg^-1水飞蓟素)、蒙花苷组(90 mg·kg^-1蒙花苷)及其代谢产物给药组(40 mg·kg^-1刺槐素、40 mg·kg^-1芹菜素、20 mg·kg^-1间苯三酚、20 mg·kg^-1对羟基苯甲酸和20 mg·kg^-1对羟基苯甲醛),每组8只;各给药组每天灌胃给药1次,连续给药7 d。除正常组外,其余各组大鼠末次给药2 h后,腹腔注射600 mg·kg^-1D-GalN造成急性肝损伤模型。用试剂盒测定血清中谷草转氨酶(GOT)和肿瘤坏死因子-α(TNF-α)的含量,用试剂盒检测肝组织中谷胱甘肽(GSH)和丙二醛(MDA)的含量。结果 正常组、模型组、阳性对照组、蒙花苷组、刺槐素组、芹菜素组、间苯三...     

三叶青总氨基酸对四氯化碳致小鼠肝损伤的保护作用

目的观察三叶青总氨基酸（TAART）对四氯化碳（CCl4）诱导的小鼠急性肝损伤的保护作用。方法选用CCl4致小鼠急性肝损伤模型,以测定小鼠血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）活性,肝脏系数,肝组织中超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量及对肝组织进行病理学检查等指标观察TAART对肝损伤的保护作用。结果TAART能明显降低CCl4致小鼠肝损伤血清ALT,AST值,降低肝脏系数及肝组织中MDA的含量,增加肝组织中SOD活性,减轻CCl4对肝脏细胞的病理损伤。结论三叶青总氨基酸对CCl4致小鼠急性肝损伤具有保护作用,其机制可能与其抗氧化作用相关。     

降酶口服液对急性肝损伤保护作用的药效学研究

目的观察降酶口服液对D-氨基半乳糖所致肝损伤的保护作用。方法动物随机分为空白对照组、模型对照组、阳性药对照组和高、低剂量给药组,连续给药5d后腹腔注射D-氨基半乳糖800mg·kg-1,观察40h后给予D-氨基半乳糖各组的肝脏指数、血清ALT、AST及病理组织学的变化,比较组间差异的显著性。结果与模型组相比用药各组的肝脏指数较低,血清转氨酶升高不明显,病理学显示用药各组的肝细胞变性、坏死明显轻于模型对照组。结论降酶口服液能阻止D-氨基半乳糖造成的肝脏指数增加,降低转氨酶,减轻肝脏病理损害,对实验性急性肝损伤有明显保护作用。     

三叶青总氨基酸对四氯化碳致小鼠肝损伤的保护作用

目的观察三叶青总氨基酸(TAART)对四氯化碳(CCl4)诱导的小鼠急性肝损伤的保护作用。方法选用CCl4致小鼠急性肝损伤模型,以测定小鼠血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)活性,肝脏系数,肝组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量及对肝组织进行病理学检查等指标观察TAART对肝损伤的保护作用。结果TAART能明显降低CCl4致小鼠肝损伤血清ALT,AST值,降低肝脏系数及肝组织中MDA的含量,增加肝组织中SOD活性,减轻CCl4对肝脏细胞的病理损伤。结论三叶青总氨基酸对CCl4致小鼠急性肝损伤具有保护作用,其机制可能与其抗氧化作用相关。     

The effects of a branched chain amino acid mixture supplemented with tryptophan on biochemical indices of neurotransmitter function and decision-making

Rationale We have previously shown that a 60-g mixture of branched chain amino acids (BCAAs) lowers the plasma availability of the catecholamine precursors tyrosine (TYR) and phenylalanine (PHE) and produces biochemical and neuropsychological changes consistent with impaired dopamine neurotransmission. However, the BCAA mixture also lowers the ratio of tryptophan (TRP) to BCAA which could impair brain serotonin function.Objectives To determine the biochemical and neuropsychological effects of a BCAA mixture supplemented with TRP.Methods We studied 32 healthy volunteers who were randomly and blindly allocated to either a single administration of amino acid mixture (60 g BCAA and 2 g TRP) or placebo. We carried out venous sampling to measure plasma levels of amino acids and performed selected cognitive tasks sensitive to monoamine manipulation 5 h after mixture ingestion.Results Relative to placebo, the BCAA/TRP mixture substantially lowered the ratio of TYR+PHE:BCAA and increased plasma prolactin. The ratio of TRP:BCAA was also lowered but to a lesser extent. The BCAA/TRP mixture produced significant changes in a task of decision-making where volunteers showed reduced discrimination between gambles with large and small losses.Conclusions A 62 g BCAA/TRP mixture decreases the availability of TYR and PHE for brain catecholamine synthesis and increases plasma prolactin consistent with lowered brain dopamine function. Addition of 2 g TRP to the 60 g BCAA mixture does not prevent a reduction of the ratio TRP:BCAA relative to placebo. The effects of the BCAA/TRP mixture on decision-making suggest a general action of dopamine pathways on the processing of emotional information in risky choice, including punishment-related cues, consistent with suggestions that dopamine mechanisms mediate behavioural responses to aversive as well as appetitive stimuli in instrumental conditioning.     

Exercise-induced changes in branched chain amino acid/aromatic amino acid ratio in the rat brain and plasma

Central fatigue was induced by running rats on a treadmill. Amino acid and ammonia metabolism in the brain and blood were followed with time to correlate its changes with physical exhaustion. The blood ammonia level did not change during running, but was prominently increased at exhaustion. The brain level of ammonia was also prominently high at the end of exercise with a time course of change similar to that of the blood level. Plasma concentrations of branched chain amino acids (BCAA) and aromatic amino acids (AAA) increased as the animals continued to run; however, the plasma BCAA/AAA ratio was definitely depressed at exhaustion. This was also true with the brain BCAA/AAA ratio. A positive correlation was demonstrated between the plasma and brain BCAA/AAA ratios at r=0.5040 and P less than 0.05. These exercise-related changes suggest that physical exercise-induced central fatigue involves not only an increase in brain ammonia, but also a disturbance in brain amine metabolism accompanying plasma and brain BCAA/AAA ratio depression. Furthermore, the ammonia level and BCAA/AAA ratio in the brain correlated with those in the blood. It is reasonable to consider that the blood ammonia concentration and plasma BCAA/AAA ratio may serve as important indices of the clinical condition of exercise-induced central fatigue.     

New therapeutic strategy for amino acid medicine: notable functions of branched chain amino acids as biological regulators

The branched chain amino acids (BCAAs) leucine, isoleucine, and valine are the most abundant of the essential amino acids. BCAAs have recently been recognized as having functions other than simple nutrition. The importance of BCAAs as nutrient regulators in protein synthesis was recognized over 20 years ago. Leucine is the most potent of the BCAAs in stimulating muscle protein synthesis, while isoleucine and valine are much less effective. The signaling action of leucine in protein synthesis has been well studied, and the mechanisms are currently under investigation. However, the pharmacological effects of isoleucine and valine have not been clarified. It has recently been reported that, among the BCAAs, leucine and isoleucine act as signals in glucose metabolism. We revealed that isoleucine stimulates both glucose uptake in the muscle and whole body glucose oxidation, in addition to depressing gluconeogenesis in the liver, thereby leading to a hypoglycemic effect in rats. Based on these results, we speculate that isoleucine signaling accelerates catabolism of incorporated glucose for energy production and consumption.     

Amikacin analogs with a fluorinated amino acid side chain

The synthesis and biological activity of kanamycin A derivatives with an omega-amino-alpha-fluoroalkanoyl side chain on the 1-amino group are described. The fluorinated amino acids (4) for the side chain were prepared by fluorination of the alpha-hydroxy esters (2) with diethylaminosulfur trifluoride (DAST) with accompanying the Walden inversion. The reaction products varied with the amino protective groups employed, chain length of the alkanoic acids and the presence or absence of base. The fluorinated side chain was introduced to 1-free-NH2 kanamycin A (12) by the conventional active ester method and subsequent deblocking reactions afforded the desired final products (13-17). Of the derivatives prepared, 1-N-[(S)-4-amino-2-fluorobutyryl]kanamycin A (2'-deoxy-2'-fluoroamikacin, 14) showed the best overall activity profile, nearly the same as that of amikacin. Preparation and antibacterial activity of several aminoglycoside antibiotics with the 1-N-(S)-4-amino-2-fluorobutyryl side chain are also discussed.     

Oral administration of branched chain amino acids improves virus-induced glucose intolerance in mice

We investigated the therapeutic effect of branched chain amino acids (BCAA) on mice with glucose intolerance induced by encephalomyocarditis virus (EMCV). Male DBA/2 mice were divided into three groups: treated with BCAA, (such as valine, leucine, and isoleucine), untreated, and control. BCAA-treated and -untreated groups were inoculated intraperitoneally with the NDK25 variant of EMCV at 200 plaque-forming units per mouse. The BCAA-treated group was administered orally 0.9 g/kg/day of each BCAA from the day after viral inoculation. The control group neither received virus inoculation nor was treated with BCAA. One week after inoculation, oral glucose tolerance tests (OGTT) were performed. After the glucose loading at 1.5 g/kg of body weight, blood glucose levels in the untreated group were 92.0+/-10.0 mg/dl at baseline, 224.6+/-10.9 mg/dl at 30 min, and 169.4+/-21.4 mg/dl at 60 min, which were significantly (P<0.05) higher than those in the control group (62. 7+/-3.6 mg/dl, 167.2+/-16.4, and 83.8+/-6.0 mg/dl, respectively). Blood glucose levels in the BCAA-treated group were 54.5+/-3.7 mg/dl at baseline, 145.2+/-8.7 mg/dl at 30 min, and 128.7+/-18.3 mg/dl at 60 min after the glucose loading, which were not significantly higher than those in the control group. Immunoreactive insulin levels at 30 min after the glucose loading were lower in the untreated group than in the control group at 1 week after virus inoculation. Histological investigations showed that the grade of insulitis in the pancreas of mice of the BCAA-treated group was lower than that of the mice of the untreated group. These results suggest that oral administration of BCAA is able to improve glucose intolerance induced by EMCV.     

Essential amino acid supplementation decreases liver damage induced by chronic ethanol consumption in rats

The liver sustains the greatest damage from ethanol (EtOH) abuse. EtOH and its metabolites impair hepatocyte metabolism, causing intracellular accumulation of proteins and lipids and increasing radical oxygen species production. These processes are toxic to the mitochondrial respiratory chain and to mitochondrial DNA. We have recently shown that supplementating the diet of rodents with an essential amino acid-enriched mixture (EAAem) significantly increases mitochondrial mass and number in cardiac and skeletal muscles and improves mitochondrial function in aged animals. Thus, in this study we sought to test whether EAAem supplementation could reduce EtOH-induced liver damage. Groups of adult male Wistar rats were fed a standard diet and water ad libitum (the control group), drinking water with 20 percent EtOH (the EtOH group), or drinking water with 20 percent EtOH and EAAem supplementation (1.5 g/kg/day) (the EtOH+EAAem group) for 2 months. The blood EtOH concentration was measured, and markers for fat (Oil-Red-O), mitochondria (Grp75, Cyt-c-ox), endoplasmic reticulum (Grp78), and inflammation (Heme Oxigenase 1, iNOS, and peroxisomes) were analyzed in the liver of animals in the various experimental groups. EAAem supplementation in EtOH-drinking rats ameliorated EtOH-induced changes in liver structure by limiting steatosis, recruiting more mitochondria and peroxisomes mainly to perivenous hepatocytes, stimulating or restoring antioxidant markers, limiting the expression of inflammatory processes, and reducing ER stress. Taken together, these results suggest that EAAem supplementation may represent a promising strategy to prevent and treat EtOH-induced liver damage.     

A dose-finding study on the effects of branch chain amino acids on surrogate markers of brain dopamine function

RATIONALE: We have previously shown in healthy volunteers that an amino acid mixture lacking tyrosine and phenylalanine reduces tyrosine availability to the brain and produces cognitive and neuroendocrine effects consistent with reduced dopamine function. This could provide a potential nutritional approach to disorders such as mania and schizophrenia, which are characterised by overactivity of dopamine pathways. The amino acid mixture we tested previously is unpalatable, whereas mixtures containing only branch chain amino acids can be made more palatable. However, the effects of such mixtures on dopamine function in humans have not been studied. OBJECTIVE: To assess the tolerability of different doses of branch chain amino acids and to measure their effects on neuroendocrine and cognitive measures sensitive to changes in dopamine function. METHODS: We used a randomised, double-blind, cross-over design in 12 healthy volunteers to assess the effect of single oral doses of 10 g, 30 g and 60 g branch chain amino acids on plasma prolactin and a test of spatial recognition memory RESULTS: The branch chain amino acids were well tolerated. The availability of tyrosine for brain catecholamine synthesis decreased in a dose-related manner. As hypothesised, the drink increased both the plasma prolactin and the latency to respond on the spatial recognition memory task. CONCLUSIONS: A drink containing branch chain amino acids is well tolerated in healthy volunteers and produces effects consistent with lowered dopamine function.     

The partial protective effect of branched chain amino acids against streptozotocin-induced cytotoxicity to mouse pancreatic islets in vitro

Recent experiments suggested that injections of branched chain amino acids (BCAA) immediately followed by streptozotocin (SZ), induced a partial protection against the diabetogenic action of SZ in vivo. In the present investigation, isolated mouse pancreatic islets were exposed in vitro to SZ (2.2-4.4 mM), with or without preincubation in a mixture of BCAA (15 mM leucine, 15 mM isoleucine and 15 mM valine). In order to evaluate the toxic action of SZ on the beta-cell, the islets were studies after culture for 3 days following SZ exposure. In control islets which had not been pretreated with BCAA, 4.4 mM SZ induced a 47% diminution in the islet number, while only 20% were lost after pretreatment with BCAA. There was also a greater total islet DNA content recovered in the islets pretreated with BCAA before SZ exposure. The BCAA islets furthermore maintained a slightly higher insulin release to the culture medium, insulin content and insulin response to an acute glucose stimulus. Preincubation with each of the amino acids alone did not protect against the SZ action. The present data are consistent with previous in vivo findings and suggest that a direct BCAA-induced decrease in the beta-cell sensitivity to SZ can explain the partial protective effect of these amino acids against the diabetogenic action of SZ.