ReviewA Review of the Role of Reactive Oxygen and Nitrogen Species in Alcohol-induced Mitochondrial Dysfunction

Our understanding of the mechanisms involved in the development of alcohol-induced liver disease has increased substantially in recent years. Specifically, reactive oxygen and nitrogen species have been identified as key components in initiating and possibly sustaining the pathogenic pathways responsible for the progression from alcohol-induced fatty liver to alcoholic hepatitis and cirrhosis. Ethanol has been demonstrated to increase the production of reactive oxygen and nitrogen species and decrease several antioxidant mechanisms in liver. However, the relative contribution of the proposed sites of ethanol-induced reactive species production within the liver is still not clear. It has been proposed that chronic ethanol-elicited alterations in mitochondria structure and function might result in increased production of reactive species at the level of the mitochondrion in liver from ethanol consumers. This in turn might result in oxidative modification and inactivation of mitochondrial macromolecules, thereby contributing further to mitochondrial dysfunction and a loss in hepatic energy conservation. Moreover, ethanol-related increases in reactive species may shift the balance between pro- and anti-apoptotic factors such that there is activation of the mitochondrial permeability transition, which would lead to increased cell death in the liver after chronic alcohol consumption. This article will examine the critical role of these reactive species in ethanol-induced liver injury with specific emphasis on how chronic ethanol-associated alterations to mitochondria influence the production of reactive oxygen and nitrogen species and how their production may disrupt hepatic energy conservation in the chronic alcohol abuser.     

Screening and evaluation of antioxidant activity of some amido-carbonyl oxime derivatives and their radical scavenging activities

The antioxidant activity of some amido-carbonyl oximes containing a C=O and –NH–R adjacent to the oxime group, [Phenyl-C(=O)-C(=N-OH)-N(-H)-Phenyl(-R)] where R= H, 4-chloro, 4-methyl, 4-methoxy, 3,4-dichloro, 3,4-dimethyl, 3-chloro-4-dimethyl, 3-chloro-4-methoxy, naphthyl and an amido-carbonyl dioxime were investigated in vitro by ferric thiocyanate, total reducing power by potassium ferricyanide reduction, 1,1-diphenyl-2- picryl-hydrazyl (DPPH^·) free radical scavenging, ferrous ions chelating, superoxide anion radical scavenging and hydrogen peroxide scavenging activity assays. The results indicated that the amido-carbonyl oximes have powerful antioxidant capacity.     

模拟空气潜水对大鼠脾组织氧自由基生成的影响

目的:观察模拟空气潜水对大鼠脾组织氧自由基(OFR)生成的影响。方法:腹腔注射自旋捕捉剂,高气压处理后检测大鼠脾组织生成的OFR。结果:模拟空气潜水后大鼠脾组织OFR生成增多,并检测到了.OH信号。结论:空气模拟潜水时呼吸气中高分压氧可促进脾组织OFR生成,主要类型可能为羟自由基。     

Effect of quercetin on chronic enhancement of spatial learning and memory of mice

In this study we evaluated the effect of quercetin on D-galactose-induced aged mice using the Morris water maze (MWM) test. Based on the free radical theory of aging,experiments were performed to study the possible biochemical mechanisms of glutathione (GSH) level and hydroxyl radical (OH-) in the hippocampus and cerebral cortex and the brain tissue enzyme activity of the mice. The results indicated that quercetin can enhance the exploratory behavior,spatial learning and memory of the mice. The effects relate with enhancing the brain functions and inhibiting oxidative stress by quercetin,and relate with increasing the GSH level and decreasing the OH-content. These findings suggest that quercetin can work as a possible natural anti-aging pharmaceutical product.     

Dual effects of copper-zinc superoxide dismutase

Copper-zinc superoxide dismutase (CuZnSOD) specifically catalyzes the removal of superoxide radicals to protect cellular function against the generation of superoxide-dependent hydroxyl radicals ((.)OH). However, an unexpected observation reveals that denatured CuZnSOD (dCuZnSOD) itself induces (.)OH formation. This dCuZnSOD-dependent (.)OH generation was not inhibited by active CuZnSOD, suggesting that it is a superoxide-independent process. Sodium cyanide, histidine, and N,N'-diethyldithiocarbamate abolished (.)OH generation, implying that Cu may be responsible for dCuZnSOD-induced (.)OH formation. Catalase eliminated ()OH generation, suggesting that hydrogen peroxide may be involved in the mechanism of dCuZnSOD-mediated (.)OH production. Furthermore, nitric oxide ((.)NO) completely inhibited dCuZnSOD-induced (.)OH radical generation, indicating that (.)NO is an important (.)OH radical scavenger. Our results shed new light on the effect of dysfunctional CuZnSOD and suggest that structural disorder of the enzyme may be one of the endogenous pathways of toxic (.)OH formation in biological systems.     

Athenolide A,a New Steroidal Lactone from the Leaves of Athenaea martiana (Solanaceae) Determined by Means of HPLC‐HR‐MS‐SPE‐NMR Analysis

Athenaea (Solanaceae) is an endemic genus belonging to the Brazilian Atlantic Rainforest. Recently, botanical investigations suggested the re‐evaluation of the generic status of the genus Athenaea as a synonym of Aureliana. In this study, the first investigation of the Athenaea genus performed on Athenaea martiana by means of HPLC‐HR‐MS‐SPE‐NMR combined with high‐resolution radical scavenging profile led to identification of several phenolic acids as radical scavengers: protocatechuic acid ( 1 ), 4‐hydroxybenzoic acid ( 2 ), caffeic acid ( 3 ), vanillic acid ( 4 ), and ferulic acid ( 6 ). Additional analysis revealed a new steroidal lactone, named athenolide A ( 9 ). Their structures were elucidated by extensive use of NMR spectroscopy as well as HR‐MS. Chemotaxonomic considerations based on these results supported the chemical relationships between the Athenaea and Aureliana genera, in agreement with the recent botanical findings.     

迷迭香对运动大鼠肝脏组织脂质过氧化损伤保护作用的研究

本实验选用SD(Sprague Dawley)大鼠,建立大强度耐力训练模型,研究迷迭香对运动大鼠肝脏组织脂质过氧化损伤保护作用。结果显示,1)迷迭香可降低血清丙氨酸氨基转移酶活性,升高肝组织丙氨酸氨基转移酶的活性,都有显著性差异(P<0.05);2)迷迭香可以不同程度地增强肝脏组织中抗氧化酶SOD(superoxide dis-mutase)、CAT(catalase)和GSH-Px(glutathione peroxidase)的活性,其中SOD和CAT的活性增加在安静和运动状态下都有显著性差异(P<0.05),GSH-Px的活性增加在运动状态下具有显著性差异(P<0.05);3)迷迭香可以降低肝脏组织中MDA(malondialdehyde)的含量,无显著性差异(P>0.05)。结论:迷迭香可以增加肝脏组织中的抗氧化酶活性,减轻大强度耐力训练对大鼠肝脏组织造成的脂质过氧化损伤。并且在同一状态下对不同的抗氧化酶活性影响不同。     

力竭游泳对大鼠不同类型肌纤维自由基代谢和血清酶的影响

本研究观察了负重力竭游泳前后大鼠不同类型肌纤维中与自由基代谢有关的若干指标 ,如丙二醛 (MDA)、超氧化物歧化酶 (SOD)和血清肌酸激酶 (CK)、乳酸脱氢酶 (LDH)、谷草转氨酶 (GOT)活性的变化     

Formation of raloxifene homo-dimer in CYP3A4, evidence for multi-substrate binding in a single catalytically competent P450 active site

Raloxifene is a polyaromatic compound which has been reported to form radicals when incubated with horseradish peroxidase resulting in formation of a homo-dimer product. Polyaromatic phenols have also been reported to undergo oxidation by P450 enzymes to form reactive intermediates, presumably through the formation of phenoxy radical species. Recently, we observed that a raloxifene homo-dimer was formed in vitro when incubated with CYP3A4. In response to this finding, a series of experiments were designed to determine whether the observed raloxifene homo-dimer was formed via solution phase chemistry similar to that previously documented with horseradish peroxidase or if generation of the homo-dimer occurred within the P450 active site. To this end, a series of experiments were carried out to determine the structure of the CYP3A4 generated raloxifene homo-dimer using analytical techniques including: high resolution MS, NMR and H/D exchange. In addition, a variety of in vitro techniques were applied to characterize the mechanism responsible for formation of the raloxifene homo-dimer. Collectively, the results of these experiments suggest that unlike the homo-dimer formed by peroxidase enzymes, raloxifene homo-dimer formation mediated by CYP3A4 is a consequence of two raloxifene molecules binding simultaneously within the active site of a catalytically competent P450 enzyme.     

Photosynthetic rate,chlorophyll fluorescence parameters,and lipid peroxidation of maize leaves as affected by zinc deficiency

Pot trial in greenhouse was conducted using cumulic cinnamon soil from North China to study the effects of zinc deficiency on CO₂ exchange, chlorophyll fluorescence, the intensity of lipid peroxidation, and the activity of superoxide dismutase (SOD) in leaves of maize seedlings. Zn deficiency resulted in a reduction of net photosynthetic rate and stomatal conductance to H₂O. The maximum quantum efficiency of photosystem 2 (PS2) and the PS2 activity were depressed, while the pool size of the plastoquinone molecules was not affected by Zn deficiency. The content of super oxygen anion radical (O₂ ^·−) and the intensity of lipid peroxidation as assessed by malonyldialdehyde content in Zn-deficient leaves were higher than those in Zn-sufficient leaves. The activity of SOD increased with Zn application. The adverse influence of Zn-deficiency on the light stage of photosynthesis is probably one of possible reasons for the limitation of photosynthetic capacity in maize leaves.