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1.
We have previously demonstrated that acute and chronic hyperprolinemia induce oxidative stress in cerebral cortex of rats. In the present study, we investigated the action of Vitamins E and C on the oxidative damage elicited by acute and chronic administration of proline (Pro) in rat cerebral cortex. Results showed that treatment with Vitamins E and C prevented the alterations caused by acute and chronic administration of proline on chemiluminescence, total radical-trapping antioxidant potential (TRAP) and on the activities of catalase and glutathione peroxidase. If these effects also occur in the human condition, it is possible that antioxidant administration might serve as a potential adjuvant therapy to avoid the progression of the neuropsychiatric dysfunction observed in hyperprolinemic patients.  相似文献   

2.
The effect of Cannabis sativa extract on acute liver injury caused by acetaminophen or carbon tetrachloride (CCl4) was studied in rats. Cannabis sativa was given at doses of 5 or 10 mg/kg (expressed as Δ9-tetrahydrocannabinol) once daily intraperitoneally (i.p.) for 2 days and simultaneously with acetaminophen or CCl4. Rats were killed 24 h after acetaminophen or CCl4 administration. Reduced glutathione (GSH), lipid peroxidation (malondialdehyde; MDA) and nitric oxide (nitrite/nitrate) concentrations were measured in the liver. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were determined in serum. Hepatic injury was also determined via histological examination of liver sections. The administration of only cannabis for 2 days had no significant effect on serum liver enzymes or on the hepatic levels of GSH, MDA or nitric oxide. However, in rats intoxicated with acetaminophen, Cannabis sativa at 5 or 10 mg/kg resulted in a significant increase in serum GOT by 17.6% and 19.5%, respectively, compared with the acetaminophen control group. In the CCl4-induced acute liver injury, the levels of AST, ALT and ALP in serum were significantly elevated by Cannabis sativa extract in a dose-dependent manner by 23.7–29.1%, 14.4–21.3% and 17.6–22.1%, respectively. In both models of hepatic injury, Cannabis sativa resulted in a significant increase in the level of liver MDA and nitric oxide and a significant decrease in GSH compared with the corresponding acetaminophen or CCl4 control group. These changes were dose dependent. Histological examination showed an increase in centrilobular necrotic areas in acetaminophen or CCl4-treated rats administered with Cannabis sativa. Histochemical investigation revealed a decrease in intracellular protein contents caused by CCl4 or acetaminophen, and these were further decreased by Cannabis sativa. It is concluded that short-term administration of Cannabis sativa enhances acute hepatic damage caused by CCl4 or acetaminophen in rats.  相似文献   

3.
目的 观察水飞蓟素磷脂复合物灌胃对硫代乙酰胺(TAA)所致大鼠急性肝损伤的保护作用。方法实验分7组,即正常对照组、模型对照组、阴性对照组(磷酯组)、阳性对照组(益肝宁组,即水飞蓟素组)、水飞蓟素磷脂复合物小、中、大剂量组。给药28天后,用硫代乙酰胺(TAA,20mg/kg)造模型。测定各组动物血清中AST、ALT、TP、ALB、LN、HA、PⅢP、CⅣ等指标的变化;并称肝重,计算肝脏指数。结果 与益肝宁(142mg/kg水飞蓟素)相比较,水飞蓟素磷脂复合物灌胃(150、300、600mg/kg)可显著降低硫代乙酰胺肝中毒模型肝损伤的严重程度。结论 水飞蓟素磷脂复合物体内保肝疗效比益肝宁为佳。该作用可能与水飞蓟素磷脂复合物比水飞蓟素的生物利用度高有关。  相似文献   

4.
The effect of Cannabis sativa extract on oxidative stress and organ tissue damage during systemic inflammation was studied. For this purpose, Swiss mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 μg/kg) to mimic aspects of mild systemic infection. Cannabis resin extract (5, 10, or 20 mg/kg) (expressed as Δ9-tetrahydrocannabinol) was given via subcutaneous route for 2 days prior to and at the time of endotoxin administration. Mice were euthanized 4 h after LPS injection. Malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (nitrite/nitrate) in the brain, liver, kidney, lung, and heart as well as brain glucose were measured. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured in liver homogenates. Histopathological examination of different organs was performed, and immunohistochemical techniques were used to evaluate expression levels of inducible nitric oxide synthase (iNOS) and caspase-3 in the brain and liver. The administration of only cannabis (20 mg/kg) decreased MDA, increased GSH, and decreased glucose level in the brain. No significant effects were observed for cannabis alone on MDA, GSH, or nitric oxide in other organs or on liver enzymes. The administration of LPS increased MDA and nitric oxide, while GSH decreased in different organs. Brain glucose increased by endotoxin. AST, ALT, and ALP were markedly increased in the liver tissue. In LPS-treated mice, cannabis (20 mg/kg) decreased MDA. GSH increased in the brain, kidney, and lung, nitric oxide decreased in the brain and lung while brain glucose decreased after the highest dose of cannabis. Cannabis failed to alter the level of liver enzymes. Histological damage in the brain, kidney, heart, lung, and liver due to endotoxin is increased by cannabis. Increased immunoreactivity of caspase-3 in the cytoplasm of the hepatocytes was observed after LPS and cannabis cotreatment compared with the LPS only group. Caspase-3 immunoreactivity markedly increased in degenerating neurons of the cortex following cannabis and LPS cotreatment. iNOS inmmunoreactivity increased after LPS and more intense iNOS expression was detected in hepatocytes after cannabis and LPS cotreatment. iNOS expression increased after cannabis and LPS treatment especially in the cerebral cortex. Thus, the administration of cannabis decreased tissue oxidative stress but increased organ damage after endotoxin injection in mice.  相似文献   

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Liver cirrhosis is an elevating cause of morbidity and mortality worldwide. TNF-α/TNF-R1 signal is implicated in progression of many liver diseases. This study provides histological and ultrastructural view that clarifies the effect of etanercept, a TNF-α inhibitor, on development of thioacetamide (TAA)-induced liver cirrhosis and the accompanied hemosiderosis in rats, highlighting the implication and distribution pattern of hepatic TNF-R1. Sixty male albino rats (Rattus norvegicus) were equally randomized into three groups. Group I served as the control. Liver cirrhosis was triggered in the other two groups by intraperitoneal injection of TAA twice a week for five months. Group II received TAA only, while group III subcutaneously injected with etanercept one hour before TAA, along five months. At the end of the experiment, blood was collected for biochemical analysis and livers were excised for histological, immunohistochemical, and electron microscopical preparations. Rats treated with TAA only developed hepatic cirrhosis accompanied by massive deposition of hemosiderin; strong and widespread expression of hepatic TNF-R1 in sinusoidal endothelial cells (SECs), Kupffer cells (KCs), and many hepatocytes; and frequent appearance of fibrogenic, plasma, and mast cells, at the ultrastructural level. By contrast, administration of etanercept diminished the expression of TNF-R1, attenuated the accumulation of collagen and hemosiderin, and preserved the hepatic histoarchitecture. In conclusion, TNF-α signal via TNF-R1 may be implicated in the mechanism of fibrogenesis and the associated hemosiderosis. Etanercept may provide a promising therapeutic approach not only for attenuating the progression of fibrogenesis, but also for hepatic iron overload-associated disorders.  相似文献   

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Severe liver damage caused by therapeutic doses of acetaminophen   总被引:3,自引:0,他引:3  
Two patients who ingested therapeutic doses of acetaminophen and who developed a severe hepatotoxicity are reported. Both patients had a rather high alcohol consumption, which probably made them susceptible to the toxic effects of acetaminophen.  相似文献   

9.
目的:探讨硫代乙酰胺(TAA)致肝性脑病(HE)小鼠肝脏和脑功能变化,寻找TAA的合适剂量和理想的观察指标。方法:设立4个TAA剂量组,分别以200、250、300、400mg/(kg.d)剂量的TAA隔24h行腹腔注射,共3次,建立不同剂量TAA致小鼠HE的动物模型,正常对照组腹腔注射生理盐水,每隔24h观察各组生存率变化,第4d进行脑功能评分、旷场实验和高架十字实验,第5d后观察其血氨和肝功指标。结果:(1)不同剂量的TAA致小鼠存活率差异,400mg/(kg.d)致小鼠存活率过低(31.6%);(2)不同剂量TAA致小鼠脑功能评分、旷场实验的总路程和中央活动时间、高架十字实验的开臂滞留时间百分比显著低于对照组(P0.05),但开臂进入次数百分比与对照组无显著差异(P0.05);(3)不同剂量TAA致小鼠血氨、AST和ALT水平显著低于对照组(P0.001),且不同剂量组之间存在显著差异(P0.001)。结论:(1)300mg/(kg.d)剂量TAA隔日腹腔注射3次为诱导小鼠A型HE模型的适宜剂量和方法;(2)TAA诱导A型HE小鼠脑功能异常,伴有自发活动减少和焦虑情绪,脑功能评分、旷场实验和高架十字实验可用于评估脑功能的变化;(3)TAA致肝功能变化呈现剂量依赖性,血氨、AST和ALT可用于评估肝功能的变化。  相似文献   

10.
Oat (Avena sativa) bran, a by-product during oat grain processing, is a excellent source of fibre, vitamins and phytochemicals. The health benefits of dietary fibre have long been established. In the present study, the antioxidant and hepatoprotective effects of oat bran extracts were investigated. The extracts showed strong 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), hydroxyl, superoxide radicals scavenging and reducing power activities in vitro. In addition, the extracts (50?mg/kg mouse) significantly reduced the levels of malondialdehyde and hepatic damage marker enzymes (aspartate transaminase and alanine transaminase), proinflammatory cytokines as well as elevated SOD, CAT, and GPx enzymes expressions in LPS-treated (1?mg/kg body weight) BALB/c mice. Therefore, the present study strongly suggests that both oat bran extracts could be excellent raw materials for manufacturing functional food due to its protective effect on hepatic liver damage and excellent antioxidant activity.  相似文献   

11.
Thioacetamide (TAA) has been used extensively in the development of animal models of acute liver injury. Frequently, TAA is administered intraperitoneally to induce liver damage under anaesthesia. However, it is rarely administered by intravenous injection in conscious rats. The experiments in this study were designed to induce acute liver damage by single intravenous injection of TAA (0, 70 and 280 mg/kg) in unrestrained rats. Biochemical parameters and cytokines measured during the 60-h period following TAA administration, included white blood cells (WBC), haemoglobulin (Hb), platelet, aspartate transferase (GOT), alanine transferase (GPT), total bilirubin (TBIL), direct bilirubin (DBI), albumin, ammonia (NH3), r-glutamyl transpeptidase (r-GT), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Rats were sacrificed by decapitation 60 h after TAA administration and livers were removed immediately for pathology and immunohistochemical (IHC) examination. Another group of rats were sacrificed by decapitation 1, 6 and 24 h after TAA administration and livers were removed immediately for time course change of pathology and IHC examination. TAA significantly increased blood WBC, GOT, GPT, TBIL, DBIL, NH3, r-GT, TNF-α and IL-6 levels but decreased the blood Hb, platelet and albumin level. The levels of histopathological damage in the liver after intravenous TAA administration were also increased with a dose-dependent trend and more increased at 60 h after TAA administration. The levels of inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) detected by IHC in the liver after intravenous TAA administration were also increased with a dose-dependent trend and more increased at 1 h after TAA administration. Single intravenous TAA administration without anaesthesia is a restorable animal model which may be used to investigate acute liver damage.  相似文献   

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This experiment evaluated Panduratin A (PA), a chalcone isolated from Boesenbergia rotunda rhizomes, for its hepatoprotectivity. Rats were subjected to liver damage induced by intra‐peritoneal injection of thioacetamide (TAA). PA was tested first for its acute toxicity and then administered by oral gavage at doses 5, 10, and 50 mg/kg to rats. At the end of the 8th week, livers from all rats were excised and evaluated ex vivo. Measurements included alkaline phosphatase (AP), alanine transaminase (ALT), aspartate transaminase (AST) and gamma‐glutamyl transferase (GGT), serum platelet‐derived growth factor (PDGF) and transforming growth factor (TGF‐β1), and hepatic metalloproteinase enzyme (MMP‐2) and its inhibitor extracellular matrix protein (TIMP‐1). Oxidative stress was measured by liver malondialdehyde (MDA) and nitrotyrosine levels, urinary 8‐hydroxy 2‐ deoxyguanosine (8‐OH‐dG), and hepatic antioxidant enzyme activities. The immunohistochemistry of TGF‐β1 was additionally performed. PA revealed safe dose of 250 mg/kg on experimental rats and positive effect on the liver. The results suggested reduced hepatic stellate cells (HSCs) activity as verified from the attenuation of serum PDGF and TGF‐β1, hepatic MMP‐2 and TIMP‐1, and oxidative stress. The extensive data altogether conclude that PA treatment could protect the liver from the progression of cirrhosis through a possible mechanism inhibiting HSCs activity.  相似文献   

15.
Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor with the effects of antioxidation, anti-inflammation and anti-fibrosis that has been shown to induce damage in liver. The purpose of this study is to investigate the effects and possible mechanisms of PTX on thioacetamide (TAA)-induced acute liver injury in rats. Male Sprague-Dawley (SD) rats were divided into four groups: control, PTX, TAA and PTX+TAA treated groups. Rats were administrated TAA together with or without PTX for a week and sacrificed 24 h after the last intragastric administration of PTX. Histopathological analysis was carried out. The liver function, the indices of oxidative stress including malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in liver tissues, and pro-inflammatory cytokines expressions were examined. The mRNA level of NF-κB p65 in liver was also determined. PTX significantly attenuated TAA-induced liver injury. The serum transaminase and MDA levels were reduced while the levels of SOD and GSH were increased, as compared with the TAA-treated group. PTX also remarkably suppressed the secretions of pro-inflammatory cytokines and the nuclear factor-κB (NF-κB) activation induced by TAA. In addition, the histopathological analysis showed that the range and degree of liver tissue lesions were improved obviously in PTX treated group. Pentoxifylline could ameliorate the effects of thioacetamide-induced acute liver injury in rats by inhibiting oxidative stress, expressions of pro-inflammatory cytokines and NF-κB activation.  相似文献   

16.
Chlorpyrifos (O,O'-diethyl-O-3,5,6-trichloro-2-pyridyl phosphorothionate, CPF) is a broad spectrum organophosphate pesticide used to control a variety of pests. The present study was undertaken to test the in vivo genotoxic potential of CPF in rats, using the single cell gel electrophoresis (or comet) assay. The rats were administered 50 mg and 100 mg CPF/kg body weight daily for 1, 2, and 3 days as well as 1.12 mg and 2.24 mg CPF/kg body weight for 90 days. The level of DNA damage was estimated by scoring 100 cells per animal, dividing into five types: types 0, I, II, III, and IV. The results clearly indicate that exposure to CPF, acutely or chronically, caused a dose-dependent increase in DNA damage in the liver and brain of rats. From the present study, it can be concluded that CPF exhibits genotoxic potential in vivo.  相似文献   

17.
目的:通过对胰岛素样生长因子结合蛋白相关蛋白1(IGFBPrP1)与硫代乙酰胺(TAA)对小鼠肝组织影响的研究,明确IGFBPrP1在肝纤维化中的作用及其机制。方法:清洁级C57BL/6野生型小鼠32只,随机分为4组:正常对照组、重组小鼠IGFBPrP1(rmIGFBPrP1)4周组、TAA2周组及TAA4周组,每组8只。取肝组织行HE、苦味酸-天狼星红及免疫组织化学染色和Westernblotting检测。结果:rmIGFBPrP14周组肝细胞广泛脂肪变性,TAA2周组出现纤维组织增生,TAA4周组病理改变较TAA2周组严重。与正常对照组相比,rmIGFBPrP14周组、TAA2周组和TAA4周组IGFBPrP1、转化生长因子β1(TGF-β1)、Smad3、p-Smad2/3、Ⅲ型胶原(ColⅢ)、I型胶原(ColⅠ)、纤维连接蛋白(FN)的表达增高(P0.05)。rmIGFBPrP14周组IGFBPrP1、ColⅠ和FN的表达与TAA2周组无显著差异。结论:IGFBPrP1在TAA诱导的肝纤维化形成过程中发挥重要作用,并可作为独立致病因子引起小鼠肝组织中细胞外基质生成增多,且该作用是通过TGF-β1/Smad3信号通路来实现的。  相似文献   

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慢性酒精中毒会对脑神经造成损伤,并且这种损伤与Aβ蛋白变化有着密切的关系。慢性酒精中毒会促进Aβ蛋白的产生,而Aβ蛋白可以激活星形胶质细胞和小神经胶质细胞,产生过多的炎症细胞因子间接损害神经,亦可通过影响线粒体的功能而损害神经元。Aβ蛋白对脑神经的损伤可表现为认知、记忆功能障碍,引发阿尔兹海默病(AD)。  相似文献   

20.
目的观察大鼠挤压伤模型中骨骼肌的变化并探讨金属硫蛋白对大鼠挤压伤骨骼肌的保护作用。方法健康雌性SD大鼠随机分为对照组、挤压伤组(CI)、挤压伤+金属硫蛋白(CI+MT)组(8只/组),全自动生化分析仪检测血清中血钾、血肌酐、血尿素氮、肌酸激酶水平的变化,HE染色观察骨骼肌与肾脏形态学改变,检测挤压部位骨骼肌湿干重比、丙二醛含量和超氧化物歧化酶活力变化。结果 CI组大鼠骨骼肌组织内可见肌纤维坏死、溶解、断裂、炎症细胞浸润,肾脏组织内可见肾小管壁肿胀、小管上皮细胞水肿、管腔变细,可见少量炎细胞浸润及蛋白管型。CI+MT组与对照组有损伤改变,但损伤程度较CI组轻;CI组骨骼肌湿干比值、丙二醛含量明显高于对照组,但CI+MT组水平低于CI组(P0.05);CI组骨骼肌超氧化物歧化酶活力明显低于对照组,但CI+MT组水平高于CI组(P0.05)。结论挤压伤缺血再灌注导致骨骼肌肌纤维损伤,外源性MT对挤压伤骨骼肌缺血再灌注损伤具有保护作用。  相似文献   

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