Protection by tetramethylpyrazine in acute absolute ethanol-induced gastric lesions

Acute oral administration of absolute ethanol (1.0 ml/kg) to fasting rats produced extensive necrosis of the gastric mucosa within 1 h. Pretreatment 30 min before administration of ethanol with oral tetramethylpyrazine (TMP) prevented this necrosis. Gross examination of the gastric mucosa of rats that received TMP showed fewer gastric lesions than that of rats who did not receive TMP. TMP pretreatment in rats exhibited superoxide scavenging activity in absolute ethanol-induced lipid peroxidation in gastric mucosal homogenates. TMP added in vitro to gastric homogenates made from control rats also showed scavenging activity. We conclude that the gastric protective mechanism of TMP could be attributed, at least in part, to its ability to inhibit lipid peroxidation and hence indirectly protect the gastric mucosa from oxidative stress.     

Increase in oxidative damage to lipids and proteins in skeletal muscle of uremic patients

Muscle weakness and reduced exercise capacity are frequent complaints of patients with chronic uremia. Several lines of evidence have suggested that chronic uremia result in a state of increased oxidative stress. Reactive oxygen species (ROS) and free radicals are capable of damaging lipids and proteins but it remains unclear whether oxidative damage plays a role in the skeletal myopathy commonly seen in chronic uremia. In this cross-sectional study, we compared the levels of oxidative damage to proteins and lipids of skeletal muscle from 40 chronic uremic patients and 20 age- and sex-matched healthy subjects. Protein carbonyls were determined by a spectrophotometric method to assess the oxidative damage to proteins. Our results showed that the mean content of protein carbonyls in skeletal muscles was significantly elevated in the hemodialysis patients ( 3.78 ±0.14 nmol of 2,4-dinitrophenyl-hydrazone per mg of protein) as compared to healthy controls (2.97 ±0.28 nmol per mg of protein, p =0.017 vs normal controls). In addition, we found that the mean malondialdehyde (MDA) level was also significantly increased in the uremic patients compared to healthy controls. Further analysis revealed that there was an age-dependent increase in both oxidative damages in these patients. Regression analysis between plasma protein carbonyl and MDA levels showed a significant correlation between these two parameters ( r =0.43, p =0.002). The finding of increased oxidative damage to protein and lipids provide support that oxidative damage may play a role in the pathogenesis of skeletal myopathy in chronic uremic patients on hemodialysis.     

丙二醛对菠菜叶片中光合羧化酶和细胞保护酶活性的影响

经丙二醛(MDA)处理的菠菜(Spinacia oleracea L.)叶片无细胞提取物中的三种与光合作用碳素还原环有关的酶 RuBPC、PEPC、GAPDH 和三种能防御活性氧毒害的酶 SOD、CAT 和 POD 的活性皆有不同程度的降低。在较低浓度的 MDA 影响下,RuBPC/O 和 GAPDH的活性已受到明显的抑制。MDA 对纯 POD(辣根)和 CAT(牛肝)的活性同样具有抑制作用,其作用是不可逆的。CAT 与 MDA 的反应引起吸收峰向长波方向漂移。半胱氨酸对 HR-POD 活性的下降具有部分保护作用。结果认为体内积累 MDA 时,由于 MDA 对酶的损伤作用,可能导致细胞代谢的进一步紊乱。     

丙二醛和Cu~（2＋）对低密度脂蛋白修饰的比较研究

实验比较了丙二醛修饰的低密度脂蛋白（ＭＤＡ－ＬＤＬ）和氧化修饰的低密度脂蛋白（ｏ－ＬＤＬ）的某些理化性质;用放射性受体分析法,从标记配体的可饱和性、可逆性、高亲和力和立体选择性等几方面,证实在小鼠腹腔巨噬细胞（ＭＰＭ）表面存在有特异的ＭＤＡ－ＬＤＬ受体,获得了一系列能反应受体特征的参数;同时,还将ＭＤＡ－ＬＤＬ受体的特征和ｏ－ＬＤＬ的受体特征进行了比较。这些结果将有助于进一步研究ＭＰＭ清道夫受体的多态性及其与动脉粥样硬化的发病原理和防治的关系。     

Artemisinin Enhances Heme-Catalysed Oxidation of Lipid Membranes

Artemisinin, a sesquiterpene endoperoxide derived from a traditional Chinese herbal remedy for fevers, is a promising new antimalarial drug, particularly useful against multidrug resistant strains of P. falciparum. Despite widespread clinical use, its mode of action remains uncertain. We investigated whether its antimalarial properties could be explained by an ability to enhance the redox activity of heme, formed in the parasite food vacuole from digested hemoglobin. Artemisinin caused a sustained threefold increase, followed by a gradual decline, in the peroxidase activity of heme. It also enhanced the ability of heme to oxidize membrane lipids about sixfold. An unexpected finding was the potentiation of heme-catalysed membrane lipid oxidation by Vitamin E. The changes in redox-catalytic activity induced by artemisinin were paralleled by major changes in the absorption spectrum of heme, culminating in loss of the Soret band. We propose a model in which artemisinin binds irreversibly to heme in the parasite food vacuole, preventing its polymerization to chemically inert hemozoin, and promoting heme-catalysed oxidation of the vacuolar membrane by molecular oxygen, which leads, ultimately, to vacuole rupture and parasite autodigestion. © 1997 Elsevier Science Inc.     

The relevance of malondialdehyde as a biochemical index of lipid peroxidation of postischemic tissues in the rat and human beings

By using a recently developed ion-pairing high-performance liquid chromatographic method for the direct determination of malondialdehyde (MDA) and several other acid-soluble low-mol-wt compounds (ascorbate, oxypurines, nucleosides, nicotinic coenzymes, high-energy phosphates), the variations of tissue and plasma MDA as a function of ischemia and reperfusion were determined in the rat (isolated Langendorff-perfused hearts and short-term incomplete cerebral ischemia) and in human beings (patients suffering from acute myocardial infarction subjected to fibrinolysis). In the rat, the data obtained indicate that, contrary to what had been previously reported in literature, MDA is not present either in control heart or in control brain. Oxygen deprivation induces the production of a low, but detectable amount of MDA in both heart and brain, whereas reperfusion causes a marked increase of MDA in both tissues. In human beings, plasma MDA was deeply affected only in patients suffering from acute myocardial infarction with successful thrombolysis, thus indicating the occurrence of oxygen radical-mediated tissue injury also in humans. On the whole, these results suggest that MDA is a valid biochemical marker of lipid peroxidation of postischemic tissues, which however needs a reliable analytical technique for its determination.     

Effects of leptin on oxidative stress in healthy and Streptozotocin-induced diabetic rats

Aims/hypothesis It is generally accepted that oxidative stress is responsible for etiology and complications of diabetes. During uncontrolled Type 1 diabetes, plasma leptin levels rapidly fall. However, it is not known whether diabetes-induced hypoleptinemia has any role in oxidative stress related to uncontrolled Type I diabetes. The present study was designed to examine the effects of leptin treatment on plasma lipid peroxidation and reduced glutathion of normal and streptozotocin(STZ)-induced diabetic rats. Methods Diabetes was induced by single injection of Streptozotocin (55 mg/kg bw). One week after induction of diabetes, rats began 5-day treatment protocol of leptin injections of (0.1 mg/kg bw i.p.) or same volume vehicle. At the end of the 5th day, rats were sacrificed by cardiac puncture under anesthesia and their plasma was taken for plasma leptin, malondialdehyde, and reduced glutathione measurements. Results Plasma leptin levels decreased in STZ-induced diabetic rats while plasma glucose, TBARS, and GSH levels increased. Plasma leptin levels were not affected with leptin treatment in both diabetic and non-diabetic rats. The elevation in plasma TBARS associated with STZ diabetes decreased with leptin treatment. Leptin also increased plasma GSH levels in diabetic rats. In non-diabetic rats, treatment with leptin did not change plasma TBARS and GSH levels. Conclusions/interpretations In conclusion, leptin treatment is able to attenuate lipid peroxidation in STZ-diabetic rats, in the onset of diabetes, by increasing the GSH levels without affecting hyperglycemia and hypoleptinemia.     

Physiological levels of tea catechins increase cellular lipid antioxidant activity of vitamin C and vitamin E in human intestinal caco-2 cells

Oxidative stress has been linked to the development of various chronic diseases. Vegetables and fruits, which contain polyphenols, were shown to have protective effects. (-)-Epigallocatechin-3-gallate (EGCG), a polyphenol abundant in tea, has been shown to have antioxidant activities in cell-free conditions and this study focused on the effect of cellular EGCG. Using an intestinal cell model to examine the oxidative stress induced by hydroxyl radicals, we report here that physiological concentrations (0.1-1 microM) of EGCG have dose- and incubation duration-dependent cell-associated lipid antioxidant activity (measuring malondialdehyde production). Vitamin E and vitamin C at 10-40 microM also showed cell-associated lipid antioxidant activities under shorter incubation durations. When EGCG was included in the incubation with vitamin E or C, more antioxidant activities were consistently observed than when vitamins were added alone. Catechin (widely present in fruits and vegetables) at 1 microM also significantly increased the antioxidant activity of vitamins E and C. Previous studies examining cell-associated activity of EGCG mainly focused on the 10-100 microM concentration range. Our results suggest that although the physiological level (0.1-1 microM) of dietary catechins is much lower than that of vitamins, they further contribute to the total antioxidant capacity even in the presence of vitamins.     

藤茶总黄酮对大鼠肝纤维化的防治作用

目的:观察藤茶总黄酮(Tengcha flavonoids,TCF)对大鼠肝纤维化的防治作用。方法:66只雄性SD大鼠被随机分为5组:正常对照组(10只),正常喂养;模型组(14只):采用四氯化碳(CCL4)皮下注射诱导大鼠肝纤维化模型;TCF治疗组分为低、中、高剂量组(每组14只):在造模的同时,每日分别予以TCF25mg/100g、50mg/100g、100mg/100g体重灌胃。于第12周末检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CⅣ)的水平以及肝组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)的含量变化。结果:与模型组比较,TCF各剂量组血清中ALT、AST、HA、LN、PCⅢ、CⅣ的水平显著下降(P<0.05);SOD活性明显增高,MDA的含量明显降低(P<0.05)。结论:TCF对CCL4实验性肝纤维化大鼠有较好的防治作用,其作用机制可能与抗氧化、抗脂质过氧化有关。     

Distribution of ethanol-induced protein adducts in vivo: relationship to tissue injury

Generation of oxygen free radicals and reactive aldehydes as a result of excessive ethanol consumption has been well established. Recent studies in human alcoholics and in experimental animal models have indicated that acetaldehyde, the first metabolite of ethanol, and the aldehydic products of lipid peroxidation can bind to proteins in tissues forming stable adducts. The demonstration of such adducts in zone 3 hepatocytes in alcoholics with an early phase of histological liver damage indicates that adduct formation may have an important role in the sequence of events leading to alcoholic liver disease. There may be interference with cellular functions, stimulation of fibrogenesis, and immunological responses. Autoantibodies towards distinct types of adducts have been shown to be associated with the severity of liver disease in alcoholic patients. High fat diet and/or iron supplementation combined with ethanol may increase the amount of aldehyde-derived epitopes and promote fibrogenesis in the liver. Recently, ethanol-derived protein modifications have also been found from other tissues exposed to ethanol and acetaldehyde, including rat brain after lifelong ethanol administration, pancreas, and rat muscle. Elevated adduct levels also occur in erythrocytes of alcoholics, which may be related to ethanol-induced morphological aberrations in hematopoiesis.