Preventive effect of taurine against acute paraquat intoxication in beagles

The continuous infusion of taurine markedly protected against paraquat (PQ)-induced oliguria in beagles. Pharmacokinetic studies revealed that taurine infusion increased the blood concentration of PQ and reduced the net content in the kidney and, to a lesser extent, in the lung. The excretion of PQ into the urine was unaltered. The infusion of glycine did not have such effects.     

Protective effect of taurine against ammonia-induced gastric mucosal lesions in rats

We examined the role of gastric ammonia in the development of gastric lesions in rats. Exposure of the gastric mucosa to ammonia (30 mM) produced microscopic injury, but no macroscopic lesion was observed. However, exposure of the stomach to ammonia in rats subjected to ischemia resulted in macroscopic gastric lesions. The macroscopic lesions were markedly inhibited by pretreatment with taurine, a scavenger of hypochlorous acid (HOCI) and monochloramine (NH2Cl). These results indicate that ammonia is deleterious to gastric mucosa, and monochloramine may be involved in the pathogenesis of ammonia-induced mucosal lesions.     

Protective effect of taurine against cyclophosphamide-induced urinary bladder toxicity in rats

1. In the present study, the effect of taurine, on cyclophosphamide (CP)-induced urinary bladder toxicity was investigated. 2. Administration of a single dose of CP (150 mg/kg, i.p.) induced cystitis, as manifested by marked congestion, oedema and extravasation in rat urinary bladder, as well as a marked desquamative damage to the urothium, severe inflammation in the lamina propria, focal erosions and polymorphonuclear leucocytes associated with occasional lymphocyte infiltration as determined by macroscopic and histopathological examination. 3. A significant decrease in the endogenous anti-oxidant compound glutathione and elevation of lipid peroxidation also resulted in rat urinary bladder tissue. 4. Cyclophosphamide-induced cystitis markedly affected the contractile function of the urinary bladder, as revealed by a significant inhibition of tissue responsiveness to acetylcholine (ACh) at different molar concentrations in vitro. 5. Conversely, pretreatment with taurine (1% in drinking water to reach a dose of 1 g/kg per day) for 7 days before and 1 day after CP injection produced a significant decrease in urinary bladder weight (oedema) and a marked decrease in vascular congestion and haemorrhage, as well as a profound improvement in histological structure. Moreover, taurine pretreatment resulted in a significant decrease in lipid peroxide in urinary bladder tissue and glutathione content was greatly restored. 6. Urinary bladder rings isolated from rats treated concurrently with taurine and CP showed a significant increase in their responsiveness to ACh compared with the CP group. 7. These results suggest that taurine offers a protective effect against CP-induced urinary bladder toxicity and may, therefore, decrease the limitation on its clinical application. These results merit extension and further investigation of the impact of taurine on CP antitumour activity.     

Protective effects of N-acetylcysteine treatment post acute paraquat intoxication in rats and in human lung epithelial cells

An animal study in rats and a cell culture study in normal human lung epithelial cells were conducted to evaluate the efficacy of N-acetyl-l-cysteine (NAC) in paraquat intoxication and associated inflammatory and oxidative stress. The effectiveness of post treatment was measured by the change of mortality rates and markers of oxidative stress, including glutathione, malondialdehyde and superoxide anion production. In addition, the levels of nitric oxide were also examined in both animal and cell culture system. NAC treatment does significantly increase the probability of survival in paraquat-intoxicated rats. It can suppress the serum malondialdehyde levels and production of superoxide anions, and conversely, augment total glutathione concentrations in all studying tissues significantly. Moreover, NAC treatment post in paraquat intoxication could reduce destruction of lung tissue, showing less inflammatory cell infiltration in interstitial stroma and mild vascular congestion. The levels of nitrite in serum and BALF were lower than those of the PQ-treated rats. Similarly, levels of iNOS expression and nitrite formation were significantly lower in normal human lung epithelial cells treated with PQ and NAC than PQ-treated alone cells.     

可乐定对梭曼中毒的预防作用(英文)

研究了可乐定对梭曼中毒的预防作用 .结果显示试管内可乐定仅在高浓度 ( 1 - 1 0 mmol· L-1)时对 Ch E产生抑制 ,在小鼠体内 1 mg·kg-1,ip时对脑 Ch E也只产生轻微的抑制 .给小鼠先 ip可乐定对梭曼中毒小鼠脑和全血 Ch E活性无明显影响 ,却使中毒小鼠惊厥发生率及死亡率显著下降 .育亨宾可以明显对抗可乐定对梭曼中毒的预防作用 .说明 α2 肾上腺素受体可能介导了可乐定对梭曼中毒的预防作用 .     

Protective effect of taurine against renal interstitial fibrosis of rats induced by cisplatin

This study was undertaken to investigate the effect of taurine on the infiltration of macrophages and the progression of renal interstitial fibrosis in the kidneys of rats treated with cisplatin (CDDP). Male rats in different groups were treated as follows: (1) saline as control, (2) CDDP and (3) CDDP plus taurine in drinking water. At weeks 2, 4 and 6 after the fifth CDDP injection, we examined platinum content, the kinetics of macrophages and the areas of fibrosis. In the histologic analyses, fibrotic areas were found to have developed around dilated or atrophic tubules in the corticomedullary junction in the kidneys of CDDP-treated rats, while CDDP-plus-taurine-treated rats showed a reduction of the extent and magnitude of damage. These findings reflect the fact that the percentage of fibrotic areas in the kidney of CDDP-plus-taurine-treated rats was significantly lower than in that of CDDP-injected rats throughout the recovery period ( P<0.05). Compared with normal rats, the macrophages in CDDP-injected rats showed significant increases in number at weeks 2, 4 and 6 ( P<0.05). In contrast, the number of macrophages in CDDP-plus-taurine-treated rats was significantly smaller than that of CDDP-injected rats. These results suggested that taurine suppressed the increase of infiltrating macrophages, and led to the attenuation of renal interstitial fibrosis ( P<0.05).     

牛磺酸对阿霉素致膈肌毒性的保护作用

目的研究牛磺酸对阿霉素致隔肌毒性的保护作用。方法家兔１８只,分３组：①对照组：静脉注射生理盐水（ＮＳ）×５ ｄ;②ＮＳ＋阿霉素组：静脉注射ＮＳ×５ ｄ;③牛磺酸＋阿霉素组：静脉注射牛磺酸 １００ ｍｇ·ｋｇ－１ × ５ ｄ。 ２、３组于末次注射后 ２ ｈ,静脉注射阿霉素 １０ ｍｇ·ｋｇ－１组注射等量ＮＳ。２４ｈ后,麻醉动物,测量跨膈压（Ｐｄｉ）、膈肌诱发电位（ＤＥＰ）。同时测定膈肌组织中丙二醛（ＭＤＡ）含量和超氧化物歧化酶（ＲＪＤ活性。电镜观察细胞器改变。结果阿霉素（ １０ ｍｇ· ｋｇ－１）可使跨膈压（ Ｐｄｉ）、膈肌诱发电位（ＤＥＰ）幅度降低（ Ｐ＜ ０． ０５）;膈肌中 ＭＤＡ含量增加, ＳＪＤ活性降低（Ｐ＜０．０５）,肌小节和线粒体形态改变。而牛磺酸１００ｍｇｋｇ－１可抑制上述现象。结论牛磺酸对阿霉素致膈肌毒性有保护作用。     

异甘草素对大鼠急性化学性肝损伤的保护作用

目的研究异甘草素(ISL)对CCl4所致大鼠急性化学性肝损伤的保护作用及其机制.方法①在体实验选用♂Wistar大鼠48只,随机分6组,每组8只.ISL三剂量给药组分别灌服ISL 10,20,40 mg·kg-1·d-1;甘草酸二铵胶囊(DG)组灌服DG 500 mg·kg-1·d-1;正常对照组和模型组每日灌服等容量的溶媒.连续给药7 d,qd.以CCl4诱导大鼠急性肝损伤模型,酶学测定各组大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)和超氧化物歧化酶(SOD)活性,以及肝组织丙二醛(MDA)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)含量.②体外实验采用大鼠离体肝细胞原代培养,并建立CCl4诱导肝细胞损伤模型,检测ISL对其作用的影响.结果①lSL剂量依赖性降低大鼠血清中升高的ALT和AST活性,升高肝组织中降低的GSH含量、SOD和GSH-Px活性,同时降低过氧化物终产物含量.②ISL浓度(5.0～20.0 μmol·L-1)依赖性抑制CCl4引起的ALT和AST升高,ISL 20.0 μmol·L-1可阻断CCl4产生的肝细胞ALT和AST漏出.结论ISL对大鼠化学性肝损伤具有显著的保护作用.其机制与清除肝组织中的自由基和抗脂质过氧化等作用有关.     

Protective effect of taurine against doxorubicin-induced cardiotoxicity in perfused chick hearts

The ability of taurine to protect the isolated heart against doxorubicin cardiotoxicity was examined. Chick hearts perfused for 20 min with medium containing 17 microM doxorubicin exhibited a decrease in contractility, an increase in resting tension and a dramatic depletion in tissue high energy phosphate content. Addition of 20 mM taurine to the perfusate attenuated the increase in resting tension and the decrease in myocardial adenosine triphosphate content induced by doxorubicin. The present study confirms our previous in vivo observations that taurine partially prevents doxorubicin-induced cardiotoxicity.     

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.     

雷公藤内酯醇对大鼠重症急性胰腺炎肺损伤的保护作用

目的：研究雷公藤内酯醇对重症急性胰腺炎肺损伤的保护作用及其可能作用机制。方法：36只雄性Wistar大鼠,随机分为3组,每组12只：假手术组（Sham组）、模型组（ALI组）和雷公藤内酯醇处理组（％组）。Sham组只行开腹术,Au组和％组经胆胰管给予牛磺胆酸钠后,分别腹腔注射生理盐水、雷公藤内酯醇0．2mg／kg。注射牛磺胆酸钠后6h处死动物。每组中6只大鼠在处死前15min静脉注射伊文思蓝（EB）20mg／kg。测定支气管肺泡灌洗液（BALF）中髓过氧化物酶（MPO）活性和中性粒细胞（PMN）数。检测肺组织湿干重比（W／D）、EB含量、MPO活性、肺组织细胞间黏附分子1（ICAM-1）及PMNCD11b／CD18表达。观察肺组织病理学的改变。结果：与Sham纽比较,ALI组肺组织病理学损伤严重,BALF中MPO、PMN水平和肺组织W／D、EB及MPO水平、ICAM-1及PMNCD11b／CD18表达水平升高（P〈0．01）;与AU组比较,Tri组上述指标均降低（P〈0．05或0．01）。结论：雷公藤内酯醇对重症急性胰腺炎肺损伤具有一定保护作用,与下调ICAM-1及PMNCD11b／CD18的表达进而抑制PMN在肺组织的聚集、激活有关。     

Protective effect of taurine on TNBS-induced inflammatory bowel disease in rats

We had previously reported that the protective effect of taurine against indomethacin-induced gastric mucosal injury was due to its antioxidant effects, which inhibited lipid peroxidation and neutrophil activation. In this study, we examined the effect of taurine on reducing the inflammatory parameters of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD), in rats. In order to induce IBD, ethanolic TNBS was given to rats intracolonically. Then they received 500 mg/kg/day of taurine orally and were sacrificed one week after IBD induction. While ulceration and inflammation of distal colon with formation of granuloma in the vehicle-treated IBD rats two days after administration of TNBS were observed, treatment with taurine ameliorated colonic damage and decreased the incidence of diarrhea and adhesion. Also, colon weight as an index of tissue edema, which was markedly increased in the IBD rats, became significantly lower after taurine treatment. Myeloperoxidase (MPO) activity in the vehicle-treated IBD rats was substantially increased, compared with that of normal control. The taurine-treated animals significantly reduced MPO activity (35% lower) when compared with that of the vehicle-treated animals. Taurine treatment decreased both basal and formyl-methionyl leucyl phenylalanine-stimulated reactive oxygen generation from colonic tissue in the IBD rats. These results suggest that the administration of taurine reduce the inflammatory parameters in this IBD rat model by increasing defending capacity against oxidative damage.     

牛磺酸对铅中毒大鼠脾的保护作用

随着工业和交通业的发展，铅对环境的污染日益加剧，严重危害人类健康。很多研究表明，铅对包括神经系统、免疫系统、生殖系统、肝、肾、脾在内的全身各系统和器官均有毒性作用。牛磺酸(taurine，Tau)是一种由含硫氨基酸转化而来的．氨基酸，广泛存在于动物及人体细胞中。据报道，Tau具有多种生理功能，     

Protective action of Omega-3 on paraquat intoxication in Drosophila melanogaster

ABSTRACT

Paraquat (PQ) (1,1?-dimethyl-4-4?-bipyridinium dichloride) is the second most widely used herbicide worldwide; however, in countries different sales and distribution remain restricted. Chronic exposure to PQ leads to several diseases related to oxidative stress and mitochondrial dysfunctions including myocardial failure, cancer, and neurodegeneration and subsequently death depending upon the dose level. The aim of this study was to examine if diet supplementation with eicosapentaenoic and docosahexaenoic acids (EPA and DHA, omega-3 long-chain fatty acids) serves a protective mechanism against neuromuscular dysfunctions mediated by PQ using Drosophila melanogaster as a model with focus on mitochondrial metabolism. PQ ingestion (170 mg/kg b.w. for 3 d) resulted in a decreased life span and climbing ability in D. melanogaster. In the brain, PQ increased thioflavin fluorescence and reduced either 4?,6-diamidino-2-phenylindole dihydrochloride (DAPI) nuclei staining and neuronal nuclei protein (NeuN) positive neurons, indicating amyloid formation and neurodegenetation, respectively. In the thorax, PQ ingestion lowered citrate synthase activity and respiratory functions indicating a reduction in mitochondrial content. PQ elevated Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) mRNA expression levels, indicative of high calcium influx from cytosol to mitochondrial matrix. In brain and thorax, PQ also increased hydrogen peroxide (H2O2) production and impaired acetylcholinesterase (AChE) activity. Concomitant EPA/DHA ingestion (0.31/0.19 mg/kg b.w.) protected D. melanogaster against PQ-induced toxicity preserving neuromuscular function and slowing down the rate of aging. In brain and thorax, these omega-3 fatty acids inhibited excess H2O2 production and restored AChE activity. EPA/DHA delayed amyloid deposition in the brain, and restored low citrate synthase activity and respiratory functions in the thorax. The effects in the thorax were attributed to stimulated mRNA expression level of genes involved either in mitochondrial dynamics or biogenesis promoted by EPA/DHA: dynamin-related protein (DRP1), mitochondrial assembly regulatory factor (MARF), mitochondrial dynamin like GTPase (OPA1), and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α). In conclusion, diet supplementation with EPA/DHA appears to protect D. melanogaster muscular and neuronal tissues against PQ intoxication.     

Protective effect of U-74389G on paraquat induced pneumotoxicity in rats

Paraquat is a very toxic herbicide and a dangerous pollutant of the environment. It forms reactive oxygen species and increases the lipid peroxidation in the pulmonary cells. Our aim in this study was to estimate the protective effects of the lazaroid U-74389G possessing antilipidperoxidation activity and membrane-stabilizing effect. The experiment was carried out with 96 male Wistar rats. Paraquat dichloride was administered orally at 80mg/kg. The lazaroid U-74389G was injected intraperitoneally twice - 2h before receiving the paraquat with 10mg/kg and four hours later with 5mg/kg. Isolated application of paraquat increased enzyme activities of lactate dehydrogenase (LDH) and acid phosphatase (AcP) and the total protein content in bronchoalveolar lavage fluid (BALF). In the same experimental group the number of polymorphonuclear cells (PMNs) in BALF is elevated significantly on days 1 and 3. The combined treatment with paraquat and U-74389G did not increase the total protein content and the number of PMNs and it elevated the enzyme activities of LDH and AcP significantly less than the alone application of paraquat. It is concluded that the lazaroid U-74389G reduces the pneumotoxic effects of paraquat, estimated by sensitive cytologic and biochemical markers in BALF. The protective effect of U-74389G is well-expressed until day 3 after the treatment.     

Protective effect of physostigmine and neostigmine against acute toxicity of parathion in rats

The effects of physostigmine and neostigmine on the parathin induced toxicity were examined in adult female rats. Physostigmine (100 μg/kg, ip) or neostigmine (200 μg/kg, ip) inhibited acetylcholinesterase (AChE) and cholinesterase (ChE) activities in blood, brain and lung when the enzyme activity was measured 30 min after the treatment. At the doses of two carbamates equipotent on brain AChE, neostigmine showed greater inhibition on peripheral AChE/ChE. The enzyme activity returned to normal in 120 min following the carbamates except in the lung of rats treated with neostigmine. Carbamates administered 30 min prior to parathion (2 mg/kg) antagonized the inhibition of AChE/ChE by parathion when the enzyme activity was measured 2 hr following parathion. Neostigmine showed greater protective effect on peripheral AChE/ChE. The effect of either carbamate on AChE/ChE was not significant 2 hr beyond the parathion treatment. Carbamates decreased the mortality of rats challenged with a lethal dose of parathion (4 mg/kg, ip) either when treated alone or in combination with atropine (10 mg/kg, ip). Lethal action of paraoxon (1.5 mg/kg, ip), the active metabolite of parathion, was also decreased by the carbamate treatment indicating that the protection was not mediated by competitive inhibition of metabolic conversion of parathion to paraoxon. The results suggest that carbamylation of the active sites may not be the sole underlying mechanism of protection provided by the carbamates.     

牛磺酸对大鼠心肌缺血再灌注损伤的保护作用

目的 探讨牛磺酸对大鼠心肌缺血再灌注损伤的保护作用及其机理。方法 采用在体大鼠冠脉结扎后再通的方法,观察牛磺酸对大鼠心肌缺血再灌注后心肌梗塞的范围,血清和心肌中SOD活性、MDA和NO含量的影响。结果 牛磺酸可明显减少大鼠心肌缺血再灌注的心肌梗塞范围（P＜0．05,0．01）,提高大鼠心肌缺血再灌注后血清和心肌中的SOD活性（P＜0．01）,降低心肌和血清中MDA和NO含量（P＜0．05,0．01）。结论 牛磺酸对大鼠心肌缺血再灌注损伤具有保护作用,可能与其提高血清和心肌组织中SOD活性、降低MDA和NO含量有关。     

The protective effect of taurine against thioacetamide hepatotoxicity of rats

Thioacetamide (TAA) administration (three consecutive intraperitoneal injections of 400 mg/kg at 24-h interval) to rats resulted in hepatic injury as assessed by the measurement of serum transaminase activities and histopathological findings. This treatment caused an increase in the levels of malondialdehyde (MDA), diene conjugates (DCs) and glutathione (GSH) and the activity of superoxide dismutase SOD ), and a decrease in the levels of vitamins E and C and the activity of glutathione peroxidase (GSH-Px) in the liver of rats. Taurine administration (400 mg/kg, i.p., every 12 h and started 24 h prior to the first TAA injection) was found to decrease serum transaminase activities and hepatic lipid peroxidation without any significant change in hepatic antioxidant system. Histopathological findings also suggested that taurine has ameliorated effect on TAA-induced hepatic necrosis. These results indicate that taurine treatment, together with TAA administration, diminished the severity of the liver injury by decreasing oxidative stress due to its possible scavenger effect.     

Protective effects of dextran sulfate and polyvinyl sulfate against acute toxicity of paraquat in mice

The protective effects of sodium dextran sulfate (SDS) and potassium polyvinyl sulfate (PPS) against the acute toxicity of paraquat (PQ) in mice were studied. The survival rates of mice treated with SDS (2000 mg/kg) or PPS (2000 mg/kg) immediately after PQ ingestion (200 mg/kg) were 100% or 100%, respectively. When treated with SDS (2000 mg/kg) or PPS (2000 mg/kg) 15 or 30 min after PQ ingestion (200 mg/kg), the survival rates were 83% or 67% for SDS-treated groups and 67% or 33% for PPS-treated groups, respectively. Treatment with SDS (2000 mg/kg) or PPS (2000 mg/kg) immediately after oral administration of PQ (200 mg/kg) increased the fecal excretion of PQ, decreased the urinary excretion of PQ and decreased the contents of PQ in the lung, liver and kidney. Such effects of SDS and PPS were reduced in the treatment with these drugs at 15 min after PQ. The in situ small intestinal absorption of PQ was significantly reduced in the presence of SDS or PPS. The binding of PQ to SDS or PPS was determined by an ultrafiltration method. These results indicate that SDS and PPS inhibit the gastrointestinal absorption of PQ on the basis of the increased intestinal transit of PQ and the binding of PQ to the drugs resulting in the protective effectiveness of SDS and PPS on the acute toxicity of PQ.