Influence of experimental diets on hepatic glutathione levels in rats with methylnitrosourea-induced mammary carcinoma

Summary Mammary tumor development induced by methylnitrosourea in female Sprague-Dawley rats had no significant effect on hepatic glutathione levels. If the diets of methylnitrosourea-treated animals were supplemented with vitamin A and E an increased hepatic glutathione level was observed initially. A high fat diet (21% per weight) supplemented with the two vitamins led to a decreased hepatic glutathione level 2 months after tumor induction. Advanced tumor development under any of the diets tested had no effect on hepatic glutathione.Dedicated to Professor D. Schmähl on the occasion of his 60th birthday     

饲克山病病区粮大鼠游离脂肪酸变化及硒和维生素E的影响

以克山病病区粮饲养大鼠１０周，用ＨＰＬＣ法测定其血浆游离脂肪酸（ＦＦＡ）含量和组成。结果表明，病区粮组血浆ＦＦＡ、Ｃ（１８：３）、Ｃ（２０：４）、ＰＵＦＡ含量增高，而Ｃ（１６：０）含量降低；同时伴有ＧＳＨ－Ｐｘ、ＣＡＴ活力降低，ＬＰＯ、ＣＫ、ＬＤＨ、α－ＨＢＤＨ含量增高。饲料中补充Ｓｅ或ＶＥ对纠正上述变化有相似但又不尽相同的效果，以联合补充效果最佳．结果提示，Ｓｅ和ＶＥ不足影响ＦＦＡ含量和组成，可能参与克山病的病因和发病机制。     

高糖、高饱和脂肪酸及高不饱和脂肪酸饮食对老年大鼠胰岛素抵抗的影响

目的 探讨不同类型高脂肪酸及高糖饮食对老年大鼠胰岛素抵抗（IR）的影响。方法 用高不饱和脂肪酸（HUFA），高饱和脂肪酸（HSFA），高糖（HS）饲料饲养大鼠24w，观察体重（BW）、总胆固醇（TC）、甘油三酯（TG）、空腹血糖（FBG）、空腹胰岛素（FINS）、游离脂肪酸（FFA）的变化，并以正常血糖高胰岛素钳夹技术的葡萄糖输注率（GIR）对大鼠IR进行评价。结果 12w和24w GIR在不同实验组间出现显著差异（均P〈0.01），HSFA组GIR最低，24w时HUFA组、HSFA组、HS组及对照组（NC组）GIR与0w相比分别下降51.6％、52.1％、34.2％、26.4％。各实验组BW、TG、TC、FFA、FBG、FINS与NC组相比有不同程度升高，经多元回归分析，GIR与FFA、TG呈显著负相关（均P〈0.01）。结论 HUFA、HSFA和HS饮食长期摄入均可诱导大鼠IR；TG及FFA的升高与IR的形成有明显相关；随月龄增长大鼠的GIR有显著下降趋势，但饮食结构的影响更重要。     

Dietary vitamin E and C intake is inversely associated with the severity of nonalcoholic fatty liver disease

Background & aimsAlthough antioxidants have a protective potential in nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), there is limited evidence regarding the role of dietary intake of antioxidants. The aim was to test the association between dietary vitamins E and C intake and NAFLD, NASH and fibrosis markers.MethodsCross-sectional study of a large cohort of subjects undergoing colonoscopy. The presence of NAFLD was evaluated by ultrasonography. The level of steatosis was defined using SteatoTest, moderate-severe NASH using new quantitative NashTest and borderline-significant fibrosis ≥ F1–F2 using FibroTest. Nutritional intake was measured by food frequency questionnaire (FFQ).ResultsOverall, 789 subjects were included (52.6% men, age 58.83 ± 6.58 years), 714 had reliable FibroMax. Adjusting for BMI, dietary and lifestyle factors, the upper tertile of vitamin E intake/1000 Kcal was associated with lower odds of NASH (OR = 0.64, 0.43–0.94, P = 0.024). There was an inverse association between reaching the recommended vitamin E intake and NASH (OR = 0.48, 0.30–0.77, P = 0.002). The upper tertile of vitamin C intake/1000 Kcal was associated with lower odds of NAFLD and NASH (OR = 0.68, 0.47–0.99, P = 0.045; OR = 0.57, 0.38–0.84, P = 0.004, respectively). Both vitamins were related with the level of steatosis according to SteatoTest.ConclusionVitamin E and C intake may be protective from NAFLD-related liver damage.     

Effect of different diets on the ratio of plasma lipids/vitamin A and E in female Sprague-Dawley rats with MNU-induced mammary carcinomas

An inverse relationship between vitamin A uptake and cancer as well as serum cholesterol concentration and cancer has been shown. An inverse relationship between serum cholesterol and retinol has also been reported. In a study, in which female Sprague-Dawley rats with MNU-induced mammary tumors were fed diets containing different amounts of fat and vitamins A and E, the effect of these diets on the inverse association between the cancer risk and both plasma lipids and vitamin A, E was investigated. According to the data obtained there is not only a relationship between plasma cholesterol and vitamin A, but also a similar relationship between cholesterol and vitamin E. The relationship between triglycerides and the two vitamins was also parallel to that of the cholesterol-vitamin A relationship. The interactions between cancer, plasma lipids and vitamin A, E could be modified by certain diets. However, further studies will be needed to elucidate these interactions.     

多烯磷脂酰胆碱联合维生素E治疗非酒精性脂肪性肝炎合并2型糖尿病患者效果研究

目的探讨多烯磷脂酰胆碱联合维生素E对非酒精性脂肪性肝炎合并2型糖尿病患者的治疗效果。方法将83例非酒精性脂肪性肝炎合并2型糖尿病患者随机分为两组,其中实验组给予多烯磷脂酰胆碱和维生素E治疗,对照组则给予多烯磷脂酰胆碱治疗,两组总疗程均为8 w。通过随访观察,对两种方法的治疗效果进行比较分析。采用空腹抽取静脉血测定血糖;采用上海丰汇医学科技有限公司提供的试剂盒测定血脂;采用上海科华生物工程股份有限公司提供的试剂盒检测肝功能指标;使用西门子Sequoia512超声诊断仪进行肝脏检查,用来评估脂肪肝程度。结果实验组和对照组血糖水平都有所下降,其中实验组为7.6 mmol/L,对照组为7.8 mmol/L,两组间差异没有统计学意义（P>0.05）;治疗后实验组ALT和AST分别为（43.8±18.2） IU/L和（42.3±9.6） IU/L,均显著低于对照组[（59.0±10.8） IU/L和（51.5±12.2）IU/L,P<0.05];治疗后实验组甘油三脂和总胆固醇分别（1.50±0.57） mmol/L和（5.09±1.18） mmol/L,均显著低于对照组[（3.00±0.29） mmol/L和（5.78±1.23）mmol/L,P<0.05];治疗后实验组肝脏B超评分为（1.2±0.3）,显著低于对照组[（1.6±0.3）,P<0.05];实验组的总有效率为79.5%,显著高于对照组（54.5%,P<0.05）。结论多烯磷脂酰胆碱联合维生素E治疗非酒精性脂肪性肝炎合并2型糖尿病患者疗效优于单纯多烯磷脂酰胆碱治疗。     

硫普罗宁联合维生素E治疗酒精性脂肪肝疗效的临床观察

目的探讨硫普罗宁联合维生素E治疗酒精性脂肪肝(AFL)的临床疗效及安全性。方法72例AFL患者随机分为两组,治疗组(46例)给予硫普罗宁0.2g每日1次静脉滴注、维生素E100mg每日2次口服;对照组(26例)给予葡萄糖醛酸内酯0.6g每日1次静脉滴注、肌苷0.4g每日3次口服。两组疗程均为1个月,观察患者治疗前后的主要症状和体征、药物不良反应、肝功能、血脂及B超下脂肪肝影像变化。结果治疗后两组比较,治疗组的症状和体征较对照组有改善(P<0.01);治疗组总有效率(80.4)高于对照组(46.2)(P<0.01);治疗组AST、ALT、γ-GT、甘油三酯(TG)较对照组降低(P<0.01),两组TBil、总胆固醇(TC)差异无统计学意义(P>0.05);治疗组脂肪肝B超分度变化较对照组有改善(P<0.01)。治疗过程中治疗组出现3例皮疹,2例低热,4例胃肠道反应。结论硫普罗宁联合维生素E治疗酒精性脂肪肝有较好的疗效,在治疗中应观察药物的不良反应。     

高脂饮食对实验性大鼠非酒精性脂肪肝UCP2表达的影响

目的:通过高脂饮食制作非酒精性脂肪肝(NAFLD)动物模型;观察高脂饮食对实验性大鼠NAFLD解偶联蛋白2(UCP2)的影响。方法:通过高脂饮食建立大鼠非酒精性脂肪性肝病模型。观察肝脏病理改变并检测肝脏UCP2表达情况。结果:与正常对照组相比,高脂饮食大鼠肝脏UCP2表达显著上升,肝组织广泛脂肪变性,形成单纯性脂肪肝。继续给予高脂饮食使肝脏UCP2表达水平进一步增加,肝脏发生进一步病理改变而形成脂肪性肝炎。结论:高脂饮食成功地复制了NAFLD动物模型;NAFLD时肝脏UCP2表达上调,可能是机体的一种适应性反应;但是UCP2过度表达,可能诱导或加剧肝脏病理改变。     

三七总甙对非酒精性脂肪肝大鼠肝组织细胞色素P450 2E1表达的影响

目的研究三七总甙对非酒精性脂肪肝大鼠肝组织细胞色素P450 2E1表达的影响。方法用脂肪乳剂灌胃法诱导大鼠非酒精性脂肪肝模型，并给予三七总甙干预，观察肝组织病理学形态的变化，采用免疫组化法检测肝组织细胞色素P450 2E1的表达，酶标仪法测定肝内丙二醛（MDA）、超氧化物岐化酶（SOD）、游离脂肪酸（FFA）含量。结果与模型组比较，三七总甙干预组肝细胞的脂肪变程度明显减轻，脂滴减少，CYP 2E1的表达受到明显抑制，肝内SOD活性升高，MDA、FFA显著降低。结论三七总甙能显著抑制大鼠脂肪肝CYP 2E1的表达，减轻脂质过氧化反应，因而具有防治脂肪肝的作用。     

A comparison of the influence of a high-fat diet enriched in monounsaturated fatty acids and conventional diet on weight loss and metabolic parameters in obese non-diabetic and Type 2 diabetic patients.

AIMS: The aim of our study was to compare the influence of a hypocaloric, high-fat diet enriched with MUFA (M) and conventional diet (C) on weight loss and metabolic parameters in obese non-diabetic and obese Type 2 diabetic subjects over a 3-month period. It was our hypothesis that the enriched diet would be more effective in decreasing blood glucose and glycated haemoglobin (HbA(1c)) than the control diet. METHODS: Twenty-seven Type 2 diabetic patients (54.5 +/- 3.5 years; DM), treated with diet or oral glucose-lowering agents, and 31 obese non-diabetic subjects (53.6 +/- 3.5 years; OB) were randomized to M or C. Individual calculations of energy requirements were based on the formula: [resting energy expenditure (REE) x 1.5] - 600 kcal. Subjects were assessed by a dietitian every 2 weeks and by a physician every month. Statistical analyses were carried out between the four groups--DM/M, DM/C, OB/M and OB/C--using pair Student's test and anova. RESULTS: After 3 months, body weight, waist-hip ratio, total body fat, levels of C-peptide, triglycerides and homeostasis model assessment (HOMA) decreased in all four groups (P < 0.01). However, fasting blood glucose and HbA(1c) decreased (P < 0.01) and high-density lipoprotein cholesterol increased significantly only in the DM/M group (P < 0.05). In general, M was well tolerated. CONCLUSIONS: Individualized M and C diets were successful in improving metabolic and anthropometric parameters in both the obese non-diabetic and the Type 2 diabetic subjects. Although the superiority of the higher fat diet did not reach statistical significance, the decline in blood glucose and HbA(1c) in the Type 2 diabetic group on M was encouraging.     

Effects of combined low‐dose spironolactone plus vitamin E vs vitamin E monotherapy on insulin resistance,non‐invasive indices of steatosis and fibrosis,and adipokine levels in non‐alcoholic fatty liver disease: a randomized controlled trial

The beneficial effects of mineralocorticoid receptor blockade by spironolactone have been shown in animal models of non‐alcoholic fatty liver disease (NAFLD). The aim of the present 52‐week randomized controlled trial was to compare the effects of low‐dose spironolactone and vitamin E combination with those of vitamin E monotherapy on insulin resistance, non‐invasive indices of hepatic steatosis and fibrosis, liver function tests, circulating adipokines and hormones in patients with histologically confirmed NAFLD. Homeostasis model of assessment of insulin resistance (HOMA‐IR) and non‐invasive indices of steatosis and fibrosis were calculated. Analysis was intention‐to‐treat. NAFLD liver fat score, an index of steatosis, decreased significantly in the combination treatment group (P = .028), but not in the vitamin E group, and the difference for group*time interaction was significant (P = .047). Alanine aminotransferase‐to‐platelet ratio index, an index of fibrosis, did not change. Insulin levels and HOMA‐IR decreased significantly only within the combination group (P = .011 and P = .011, respectively). In conclusion, the combined low‐dose spironolactone plus vitamin E regimen significantly decreased NAFLD liver fat score. Larger‐scale trials are needed to clarify the effect of low‐dose spironolactone on hepatic histology.     

Mechanism of action of gypenosides on type 2 diabetes and non-alcoholic fatty liver disease in rats

AIM:To explore the mechanism of action of gypenosides(GPs)on type 2 diabetes mellitus and non-alcoholic fatty liver disease(T2DM-NAFLD)in rats.METHODS:Sixty rats were randomly divided into a healthy group,an untreated disease model group andGP-treatment groups.The study involved the evaluation of biochemical parameters,including serum aspartate transaminase(AST),alanine transferase(ALT),blood glucose(BG),triglycerides(TG)and total cholesterol(TC).Additionally,the protective effect of the treatments were confirmed histopathologically and the expression of TNF-αand NF-κB in the rat liver was analyzed using immunohistochemistry.The expression of proliferatoractivated receptor gamma(PPARγ)and cytochrome P450(CYP450)1A1 m RNA was determined by quantitative RTPCR.RESULTS:GP treatments at oral doses of 200,400,and800 mg/kg per day significantly decreased the levels of serum AST and ALT(P0.05,P0.01),especially at the dose of 800 mg/kg per day.To a similar extent,GP at800 mg/kg per day reduced the levels of BG(4.19±0.47,P0.01),TG(80.08±10.05,P0.01),TC(134.38±16.39,P0.01)and serum insulin(42.01±5.04,P0.01).The expression of TNF-αand NF-κB measured by immunohistochemistry was significantly reduced by GPs in a dose-dependent manner,and the expression of PPARγand CYP4501A1 m RNA,as measured using quantitative real-time PCR,were significantly down-regulated by GPs.Moreover,GPs decreased the infiltration of liver fats and reversed the histopathological changes in a dosedependent manner.CONCLUSION:This study suggests that GPs have a protective effect against T2DM-NAFLD by down-regulating the expression of TNF-αand NF-κB proteins,and PPARγand CYP4501A1 m RNAs.     

胆碱-蛋氨酸缺乏饲料诱导的非酒精性脂肪肝大鼠chemerin及其受体的表达

目的 探讨胆碱.蛋氨酸缺乏饲料(MCD)诱导非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)不同时期大鼠肝脏chemerin及其受体(chemokine-like receptor 1,CMKLRI)表达的动态变化.方法 Wistar大鼠随机分为对照组和MCD组.适应性喂养1周后,分别给予普通饲料和MCD饲料喂养,分别在喂养1、4、10周时处死.检测血清谷丙转氨酶(alanine transarninase,ALT)、血脂、肝功能及肝脏TG含量,并做HE染色观察肝脏形态变化;采用实时荧光定量PCR检测细胞因子chemerin及CMKLR1 mRNA水平的表达变化,并用Northern印迹进一步确认chemerin mRNA水平的表达变化.Western印迹检测小鼠血清chemerin水平.结果 MCD饲料喂养1、4和10周后,MCD组肝脏chemerin的mRNA表达逐渐下降(1.00±0.08对0.72±0.10;1.00±0.24对0.63±0.31;1.00±0.05对0.50±0.13);CMKLR1表达逐渐上升(1.00±0.14对0.84±0.26;1.00±0.38对1.51±0.33;1.01±0.13对1.84±0.39).血清chemerin含量减少(1.00±0.11对0.96±0.39;1.00±0.12对0.21±0.77;1.00±0.42对0.21±0.11).结论 Chemerin及其受体的表达变化可能参与了MCD饲料诱导的非酒精性脂肪肝的发病过程.     

Endothelial dysfunction in Type 1 diabetes mellitus: relationship with LDL oxidation and the effects of vitamin E.

AIMS: To examine the hypothesis that increased susceptibility of low density lipoproteins (LDL) to oxidation predisposes to endothelial dysfunction in patients with Type 1 diabetes mellitus. METHODS: A cross-sectional study of 46 non-nephropathic diabetic and 39 control subjects and in the diabetic patients, a 3-month duration, randomized, placebo-controlled double-blind trial of vitamin E 500 U/day. Flow-mediated vasodilatation (FMD) was measured in the forearm by high resolution ultrasound. LDL oxidation by Cu2+ was measured in vitro. RESULTS: Diabetic patients had greater basal and reactive forearm blood flow (geometric mean (SD%) flow (ml/min) 110.15 (19.19%) vs. 74.99 (23.17%); P=0.045, and 344.35 (20.84%) vs. 205.17 (21.48%); P=0.007), compared with controls, but there was no difference in FMD (median (interquartile range) 0.00 (-0.01-0.02) vs. 0.02 (-0.01-0.02) cm2; P=0.78). Diabetic LDL oxidation lag time correlated with postdilatation brachial artery area (r= 0.32; P=0.05) but not with FMD. Lag-times and total LDL oxidation by Cu2+, lipoprotein and vitamin E concentrations were similar in diabetic and control groups. Antibody titres to oxidized LDL (oxLDL) were higher in non-diabetic than diabetic subjects, and were unrelated to FMD. In diabetic patients, vitamin E increased mean (SD) plasma vitamin E levels (24.0 (6.5) to 47.5 (7.5) gmol/l; P=0.0006) and resulted in increased FMD (delta 0.00 (-0.02-0.01) vs. 0.01 (0.01-0.02)) cm2; P=0.0036), but no changes in LDL Cu2+ oxidation profiles were observed. CONCLUSIONS: FMD is no different in Type 1 diabetic and non-diabetic subjects and nor are indices of lipid peroxidation and in vitro LDL oxidation although levels of antibody to oxLDL are lower in diabetes. Vitamin E supplementation increases plasma vitamin E levels and may enhance FMD in diabetes but, in the absence of changes in LDL oxidation, this may not be mediated by reduced oxidation of LDL.     

维生素E、硒对非酒精性脂肪肝大鼠肝细胞色素P4501A1及脂质过氧化的干预作用

目的:研究维生素E、硒对非酒精性脂肪肝大鼠肝细胞色素P4501A1及脂质过氧化的干预作用.方法:♂SD大鼠,随机均分为5组:对照组(普通饲料)、模型组(高脂饲料)、VE干预组、Se干预组、VE Se干预组,建模5wk处死全部大鼠.生化方法检测血清及肝组织超氧化物歧化酶(SOD)和丙二醛(MDA)含量的变化,逆转录聚合酶链反应(RT-PCR)测定肝细胞色素P4501A1mRNA表达的变化,免疫组化方法测定肝组织中肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)表达的变化.结果:与对照组比较,模型组血清及肝组织中SOD显著降低(312.72±49.51kU/Lvs583.23±63.37kU/L;8.13±0.63U/mgprot.vs13.99±2.33U/mgprot.,P<0.01),MDA增高(13.40±4.24mmol/Lvs6.43±1.76mmol/L;9.79±0.94nmol/mgprot.vs6.80±0.97nmol/mgprot.P<0.01),细胞色素P4501A1mRNA表达水平,肝组织TNF-α、NF-κB蛋白表达明显增强(0.628±0.116vs0,0.230±0.013vs0.03±0.006,0.069±0.01vs0.003±0.001;P<0.05).与模型组比较VE组、Se组的血清及肝组织中SOD增高,MDA降低,细胞色素P4501A1mRNA表达水平略下降;肝组织TNF-α、NF-κB蛋白表达下降(P<0.05).VE Se组与模型组比较,血清SOD明显增高,其值接近对照组水平;细胞色素P4501A1mRNA表达水平显著下降(0.324±0.070vs0.628±0.116,P<0.05).结论:非酒精性脂肪肝的脂质过氧化损伤及相关因子的表达可能与肝细胞色素P4501A1表达上调有关.VitE和硒能提高机体的抗氧化能力,对非酒精性脂肪肝有保护作用,二者联合作用更明显.     

非酒精性脂肪性肝病与乙型肝炎病毒既往感染者肝癌发生关系的研究

目的:乙型肝炎表面抗原（HBsAg）清除并不能消除乙型肝炎病毒（HBV）感染患者的肝细胞癌（HCC）风险,本研究旨在探讨非酒精性脂肪性肝病（NAFLD）在HBV既往感染者（HBsAg阴性、抗-HBc阳性）HCC发生中的作用。方法:本研究是回顾性调查研究,纳入2015年至2017年在南方医院住院并首次诊断为HCC的患者共...     

老年代谢综合征患者血清游离脂肪酸与胰岛素抵抗的相关性研究

目的探讨老年代谢综合征（MS）患者中血清游离脂肪酸（FFA）水平与胰岛素抵抗（IR）的相关性。方法选取2009年1月至2010年6月上海交通大学附属第一人民医院老年科住院患者96例,年龄≥65岁。采用2005年国际糖尿病联盟提出的标准,分为MS组38例及非MS组58例,分别检测血清FFA、胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆同醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、空腹血糖（FBG）、空腹胰岛素（FINS）,用稳态模式（HOMAModel）公式计算HOMA—IR评估胰岛素抵抗。分别测各组体重、腰围、身高,计算体质指数（BMI）。结果1、MS组的身高、体重、腰围、BMI、FBG、FINS及HOMA—IR、TC、HDL—C、TG水平均高于非MS组（P〈0．01）,MS组的FFA水平高于非MS组（P〈0．01）;2、直线相关分析显示在MS组中FFA水平与FBG、FINS、HOMA-IR呈正相关（P〈0．05）;3、多元逐步回归分析结果显示FFA与HOMA—IR独立相关（P〈0．05）。结论老年MS患者FFA升高,FFA水平与m存在相关性,FFA是老年MS患者IR的独立危险因素。     

Protective effects of a combination of quercetin and vitamin E against cyclosporine A-induced oxidative stress and hepatotoxicity in rats.

Aim: Cyclosporine A (CsA) is the most widely used immunosuppressive drug in transplant surgery. It is able to generate reactive oxygen species (ROS) and cause lipid peroxidation (thiobarbituric acid-reacting substances [TBARS]), which will directly result in CsA hepatotoxicity. Methods: In this study, the potential of quercetin (Q) and vitamin E (E), in attenuating CsA-induced liver dysfunction in rats was investigated. Male Sprague-Dawley rats were divided into six groups and treated with either olive oil, ethanol + olive oil, CsA, CsA + E, CsA + Q, or CsA + E + Q for both 4 and 8 weeks. Hepatotoxicity was assessed by morphological alterations in tissue architecture and by reduced serum total protein and increased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Results: The results indicated that CsA treatment increases TBARS and decreases activities of catalase (CAT) and glutathione peroxidase (GPx) in the rat liver. The co-administration of E and Q with CsA treatment improved both liver morphology changes and function. A combination of these antioxidants significantly reduced TBARS and increased CAT and GPx activities in the hepatic tissue. Conclusion: Our data demonstrates that E + Q plays a protective role against the imbalance elicited by CsA between the production of free radicals and antioxidant defence systems, and suggests that a combination of these two antioxidants may find clinical application where cellular damage is a consequence of ROS.     

Study on association of non-alcoholic fatty liver disease and serum vitamin A,E, and selenium levels in high-fat fed diet rats

International Journal of Diabetes in Developing Countries - Non-alcoholic fatty liver disease (NAFLD) has become the most common cause of fatty liver disease, which occurs due to the accumulation...