Reactive oxygen species and human spermatozoa: physiology and pathology

The role of reactive oxygen species (ROS) in the pathophysiology of human sperm function has been emphasized in recent years. ROS production in semen has been associated with loss of sperm motility, decreased capacity for sperm–oocyte fusion and loss of fertility. There is a current presumption that the most prolific source of ROS in sperm suspensions is an NADPH oxidase located in leukocytes or in spermatozoa which produces superoxide which is further converted to peroxide by the action of superoxide dismutase. Hydrogen peroxide has been recognized as the most toxic oxidizing species for human spermatozoa, which are very sensitive to lipid peroxidation owing to the high content of polyunsaturated fatty acids in their plasma membrane, though this is not the sole mechanism by which sperm function might be impaired by ROS. Although the excessive production of ROS is detrimental to human spermatozoa, there is a growing body of evidence which suggests that ROS are also involved in the physiological control of some sperm functions. This review focuses on the nature and source of the ROS generated by human spermataozoa as well as their operational mechanisms and their effects, which may be detrimental or beneficial.     

Lipid peroxidation in several brain regions during development of post-stress depressions in rats with different strategies of adaptive behavior

Lipid peroxidation in the brain cortex, striatum, hippocampus, and hypothalamus of rats of the KLA and KHA lines which were distinguished by their strategies of adaptive behavior was investigated following emotional-painful stress. Significant long-term changes in lipid peroxidation were shown to occur in the brain. These had a phase character and depended on the behavioral characteristics of the animals. The investigated brain regions were characterized by different reactions of lipid peroxidation to the stress. The induced depressive-like states (on the 21st day after the stress) in rats of the KLA and KHA lines were distinguished by the largest changes in lipid peroxidation in the striatum and hypothalamus and in the striatum and hippocampus, respectively. One could conclude on the basis of these results that both identical and different mechanisms of formation and development of depression existed in the animals with different behavioral strategies.     

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.     

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.     

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。     

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     

同型半胱氨酸对胚胎海马神经元细胞的影响

目的 观察同型半胱氨酸(homocysteine，HCY)对海马神经元细胞分化和增殖的作用机理。方法 采用大鼠胚胎海马神经元细胞进行体外培养。观察不同浓度的HCY(0．01、0．1、1．0、10．0、100．0)mmol／L对细胞分化和增殖的影响。结果 随着剂量的增加．同型半胱氨酸对胚胎海马神经元细胞分化和增殖具有抑制作用，并用流式细胞术分析证明对脂质过氧化(LPO)的影响而使得神经元蛋白质含量增高。结论 同型半胱氨酸可抑制胚胎海马神经元细胞分化和增殖的影响，HCY可能在导致神经管畸形的过程起着重要作用。     

刺梨汁对慢性氟中毒的影响及机理研究

用高氟饲料喂养大鼠６个月，复制出慢性氟中毒模型，再自由饮用刺梨汁３个月，探讨刺梨汁对慢性氟中毒的影响及机理。结果表明：刺梨汁可明显改善氟中毒的一般状况，对已形成的氟斑牙影响不大，但可促进尿氟排泄，降低血清和骨氟含量及尿羟脯氦酸含量，提高血清中维生素Ｃ、维生素Ｅ和血清、肝、肾ＧＳＨ含量，增强血、肝、肾ＧＳＨ－Ｐｘ和ＳＯＤ活性，降低血清、肝和肾ＬＰＯ含量，降低尿γ－ＧＴ和血清ＧＰＴ活性及肝ＴＧ含量，提示：刺梨汁具有明显桔抗慢性氟中毒作用，其机理可能是通过促进尿氟排泄和抗氧化作用。     

Effect of pentoxifylline on veno-occlusive priapism-induced corporeal tissule lipid peroxidation in a rat model

Objective: To investigate whether pentoxifylline could play a role in attenuation of the hazardous effects of ischemia/reperfusion on corporeal tissue in a rat model of veno-occlusive priapism (VOP). Materials and methods: Placebo and pentoxifylline were given to eight groups of rats prior to priapism being induced by a vacuum constrictive device for durations of 6 and 12 h, respectively. Half of the groups of rats that underwent the same duration of priapism (ischemic) were subjected to 1 h of detumescence after band removal (reperfusion). One group underwent no manipulation and no drug administration and served as a baseline determination (control). Corporeal homogenates were examined for lipid peroxidation (LP) derived malondialdehyde (MDA) accumulation via thiobarbituric acid assay. Results: MDA concentration differed significantly between VOP rats and controls (P < 0.001) but did not differ significantly between ischemic-only groups and reperfused groups (P > 0.05). In the pentoxifyllinepretreated groups, although MDA accumulation tended to be slightly lower than in the placebo groups, the difference was not statistically significant (P > 0.05) either in the 6- or 12-h duration priapic groups. Conclusions: LP, an indicator of radical oxygen metabolite (ROM) induced injury, occurs in rat corporeal tissue during and after abolishment of VOP. Single-dose pentoxifylline pretreatment failed to exert a protective effect on corporeal tissue in a rat model of VOP in terms of attenuation of LP.