Toxic effects of Fusarium mycotoxin butenolide on rat myocardium and primary culture of cardiac myocytes.

Mycotoxin toxicosis has been implicated in the etiopathogenesis of Keshan disease (KD), an endemic cardiomyopathy prevailing in some regions of China. Butenolide (4-acetamido-4-hydroxy-2-butenoic acid gamma-lactone, CAS No. 16275-44-8), a mycotoxin produced by several Fusarium species such as Fusarium tricinctum and Fusarium graminearum, is frequently detected from the cereals in the endemic areas of KD. The present study is undertaken to investigate whether this mycotoxin can induce myocardial damage. Exposure of primary culture of cardiac myocytes to butenolide resulted in significant cytotoxicity, manifested by changes in cell morphology and decreases in cell viability. Consistent with the in vitro findings, distinct myocardial toxicity in vivo was observed after administration of rats by gavage with butenolide (10 and 20 mg/kg/day) for 2 months, and the myocardial injuries were characterized by focal necrosis of myocardium and fragmentation of myofiber. Butenolide also induced significant oxidative damage to the myocardium in vitro evidenced by a concentration-dependent lipid peroxidation in the myocardial homogenates, whereas antioxidants superoxide dismutase (SOD), N-acetylcysteine (NAC) and glutathione (GSH) provided significant protections against this oxidative effect. Taken together, these results clearly reveal that butenolide possesses the potential to induce myocardial toxicity. The present findings may reinforce the hypothesis that toxicosis by mycotoxins is one of the etiological factors for KD.     

车前子对高脂血症大鼠脂质过氧化的影响

目的 :　探讨车前子对高脂血症大鼠脂质过氧化的影响。方法 :　采用大鼠血清及多脏器组织 ,观察车前子对高脂血症大鼠脂质过氧化的影响。结果 :　高脂对照组血清和心肌超氧化物歧化酶 ( SOD)活性显著降低 ,而脂质过氧化物 ( LPO)含量明显升高 ,血清和肝脏的过氧化氢酶( CAT)、谷胱苷肽过氧化物酶 ( GSH-Px)活性明显降低。补充车前子后显著升高血清及心肌组织SOD活性 2 2 %和 2 8% ,以及肝脏 GSH-Px活性 2 2 %。而使血清及心肌的 LPO含量分别下降 3 2 %和 1 7%。结论 :　 1 5 g/kg车前子可提高高脂血症大鼠体内抗氧化能力并免受自由基损伤     

The Protective Role of Glutathione, Cysteine and Vitamin C against Oxidative DNA Damage Induced in Rat Kidney by Potassium Bromate

The roles of glutathione (GSH), cysteine, vitamin C., liposome-encapsulated superoxide dismutase (L-SOD) and vitamin E in preventing oxidative DNA damage and cytotoxicity in the rat kidney after administration of potassium bromate (KBrO₃) to male F344 rats were investigated by measuring 8-hydroxydeoxyguanosine (8-OH-dG), an oxidative DNA product, lipid peroxidation (LPO) levels and relative kidney weight (RKW). Combined pre- and posttreatment of animals with 2 × 800 mg/kg GSH i.p. inhibited the increase of 8-OH-dG, LPO levels and RKW caused by 80 mg/kg KBrO₃ i.p. administration. In contrast, pretreatment with 0.3 ml/kg diethylmaleate (DEM) i.p., a depletor of tissue GSH, was associated with elevation of 8-OH-dG, LPO levels and RKW after a 20 mg/kg KBrO₃ i.p. treatment, which itself caused no change. Administration of KBrO₃ itself reduced renal non-protein thiol levels, but this was inhibited by the two doses of exogenous GSH. Combined treatment with DEM and KBrO₃ lowered the non-protein thiol level in the kidney more than did DEM treatment alone. Protective effects against the oxidative damage caused by KBrO₃ were also observed for pre- and posttreatment with 400 mg/kg cysteine i.p., another sulfhydryl compound, and daily i.g. application of 200 mg/kg vitamin C for 5 days. However, no influence was evident after pre- and posttreatment with 18,000 U/kg L-SOD i.p. or daily i.g. 100 mg/kg of vitamin E for 5 days. The results suggest that intracellular GSH plays an essential protective role against renal oxidative DNA damage and nephrotoxicity caused by KBrO₃.     

穿心莲乙酯对大鼠心肌缺血再灌注损伤的保护作用

本实验观察了穿心莲注射液对大鼠心肌缺血再灌注损伤的影响。结果显示:穿心莲(2.5mg·kg~(-1),iv)可保护缺血再灌注心肌SOD活性(P<0.01),降低MDA含量(P<0.001),明显降低严重心律失常发生率。提示穿心莲注射液对缺血再灌注心脏具有保护作用,其抗脂质过氧化作用可能系其作用机制之一。     

六味地黄汤对实验性糖尿病大鼠心、肝、肾组织中过氧化氢酶活性和过氧化脂质含量的影响

用四氧嘧啶诱导雄性Ｗｉｓｔａｒ大鼠为模型进行研究．结果发现，四氧嘧啶大鼠血糖明显升高，且心、肝、肾组织中过氧化氢酶活性较正常组明显降低，过氧化脂质含量在心、肝组织中明显增高，过氧化脂质与过氧化氢酶比值在心、肝、肾组织中均明显高于正常组，表明糖尿病状态下大鼠心、肝、肾组织中均自由基生成增多，氧化损伤加重．经六味地黄汤治疗后，血糖明显下降，但心、肝、肾组织中的过氧化氢酶活性无改变；而心肌中过氧化脂质含量和过氧化脂质与过氧化氢酶比值则明显降低，过氧化脂质含量和过氧化脂质与过氧化氢酶比值在肝、肾组织中无变化，表明六味地黄汤能明显清除心肌中自由基，抑制心肌中脂质过氧化，且此作用并不是通过提高过氧化氢酶活性来达到．     

Lipid Peroxidation and Vitamin E in Red Blood Cells and Plasma in Hemodialysis Patients Under rhEPO Treatment

Abstract: Lipid peroxidation, measured by malonyldial-dehyde (MDA) and vitamin E in red blood cells (RBC) and plasma, was investigated in 25 hemodialysis (HD) patients before and after 6 months rhEPO therapy. RBC-MDA was significantly elevated, but plasma MDA was in the reference range. After recombinant human erythro-poietin (rhEPO) treatment, the MDA level was significantly decreased in both compartments. Marked vitamin E deficiency was established in RBC as well as in plasma. rhEPO therapy restored vitamin E levels in both compartments. Our data suggest a possible positive rhEPO-antioxidant effect in HD patients.     

核黄素缺乏大鼠红细胞维生素E水平的变化及脂质过氧化关系的研究

对两组大鼠分别喂饲核黄素缺乏（ＲＤ）膳和核黄素添加（Ｒ８，２２ｍｇ／ｋｇ饲料）膳８周后，测定了两组大鼠的红细胞维生素Ｅ（ＲＢＬＶｅ）、红细胞超氧化物歧化酶（ＳＯＤ）和红细胞丙二醛（ＭＤＡ）的水平。结果发现：ＲＤ组ＲＢＣＶｅ水平（４．７１７３±０．７７１０ｍｇ／ｇ蛋白质）显著低于ＲＳ组（５。３８６８±１．１５３７ｍｇ／ｇ蛋白质，Ｐ＜０．０５）。而ＲＤ组的ＲＢＣＳＯＤ（７７４５．２±６１０．１ｕ／ｇ蛋白质）和ＭＤＡ（０．６８６８±０．１３７２μｇ／ｇ蛋白质）则分别显著低于和高于ＲＳ组（８２６８．５±３０１．０ｎｕ／ｇ蛋白质，０．５５４８±０．０９８０，Ｐ＜０．０５）。研究提示，核黄素缺乏引起细胞膜脂质过氧化加重可能ＲＢＣＶｅ消耗增加。     

硒对辐射所致过氧化脂质含量及谷胱甘肽过氧化物酶活性的影响

以肝、脾组织中过氧化脂质(LPO)含量及谷胱甘肽过氧化物酶(GSHL-Px)活性为指标探讨硒的辐射防护效应。实验结果表明:BALB/C纯系雄性小鼠经3Gy ~(60)Co γ射线照射后3天,肝、脾组织LPO生成量比未照射者均显著增多,而GSH-Px活性却都显著降低;但于照射前连续7天每日经口灌胃亚硒酸钠溶液0.2ml(含硒12.5μg)的实验组动物,肝、脾组织LPO含量均明显少于照射对照组,而GSH-Px活性都显著高于照射对照组,结果提示,通过降低LPO含量和增加GSH-Px活性,硒对小鼠可能有辐射防护作用。     

复合膳食纤维对大鼠体内脂质过氧化作用的影响

制备复合膳食纤维 (dietaryfiber,DF) ,并分别探讨复合、混合及三种单一的DF对高脂血症大鼠体内脂质过氧化作用的影响。选健康、断乳Wistar大鼠 6 4只 ,按体重随机分为 8组 ,用高脂饲料诱发高脂血症的同时 ,分别添加 10 %的DF :纤维素 (B组 )、果胶 (C组 )、海藻酸钠 (D组 )、纤维素 -果胶复合物 (E组 )、纤维素 -海藻酸钠复合物 (F组 )、纤维素 -果胶混合物 (G组 )、纤维素 -海藻酸钠混合物 (H组 ) ,以单纯的高脂饲料组为对照组 (A组 ) ,观察各种DF对大鼠的生长发育及脂质过氧化作用的影响。结果显示 :1、添加 10 %的各种DF不影响大鼠的生长发育。 2、各种DF皆可显著升高血清超氧化物歧化酶 (SOD) (P <0 0 1)、谷胱甘肽过氧化物酶 (GSH Px)活性 (P <0 0 1) ,降低丙二醛 (MDA)水平 (P <0 0 5 ,B、D组除外 ) ,提高红细胞膜的流动性 (P <0 0 5 ) ,以复合物、混合物效果为明显。 3、各种DF可不同程度地增加粪重和粪脂排出量 (P <0 0 5 ,D组除外 ) ,以复合物、混合物为明显。提示各种DF皆可不同程度地降低大鼠体内脂质过氧化作用 ,提高红细胞膜的流动性 ,其中可溶性DF效果优于不可溶性DF ,而复合、混合DF的效果又优于单一的DF ,且以复合物效果为佳