Infection and reactive oxygen species

Summary. In previous years the physiologic and pathophysiologic significance of reactive oxygen species (ROS) on sperm function has been recognized. The impact of ROS during the invasion, adhesion and multiplication of microorganisms in the male genital tract are largely unknown. However, it is known that the resulting activation of leukocytes leads to an increased generation of ROS. There is growing evidence that spermatozoa are protected from detrimental ROS effects by the powerful antioxidants in seminal plasma since disturbances of sperm function by ROS were demonstrated in the absence of seminal plasma, i.e., during epididymitis or after semen preparation. If seminal plasma is present, ROS generated by physiologic numbers of granulocytes (< 1 times 10⁶ ml⁻¹) apparently do not damage spermatozoa. Interestingly, ROS generated by leukocytes during male genital tract infections are critical for the techniques of semen preparation for assisted reproduction. These ROS impair sperm function if the protective effects of seminal plasma are not present. The relevance of ROS production by higher leukocyte numbers in human semen is presently unknown as is the relevance of ROS generated in the female reproductive tract.
In previous years the ambiguous role of reactive oxygen species (ROS) generation in human semen has been recognized. On one hand, ROS appear to be involved in physiologic reactions such as capacitation (De Lamirande & Gagnon, 1995; Griveau et al. , 1995a), while on the other hand, there is ample evidence that an increased ROS production impairs sperm functions and the fertilizing capacity of spermatozoa (Ochsendorf & Fuchs, 1993; Aitken, 1994; Griveau et al. , 1995b). The objective of this review is to summarize the relevance of reactive oxygen species during infections of the male genital tract.     

精子功能与氧自由基

本文综述了精液内氧自由基的产生系统和拮抗系统 ,以及氧自由基对精子功能和形态的影响。精液中一定水平的氧自由基是精子获能和发生顶体反应所必需的 ,但氧自由基生成量增加 ,超过精子所需的生理剂量 ,则会导致精子受损 ,影响人类受精和家畜繁殖     

Targeting reactive oxygen species in hypertension

PURPOSE OF REVIEW: Hypertension is a major risk factor for vascular diseases such as stroke, myocardial infarction, and renal microvascular disease. The mechanism by which vascular disease develops is complex, and growing evidence suggests that an increase in reactive oxygen species during hypertension is a major contributing factor. NADPH oxidase, the primary source of reactive oxygen species in the cardiovascular system, is a strong candidate for the development of therapeutic agents to ameliorate hypertension and end-organ damage. RECENT FINDINGS: Various scavengers and inhibitors of reactive oxygen species have been proposed for use in animal as well as human studies. While many of these agents are effective at lowering tissue reactive oxygen species levels, their specificity is a serious concern. Our laboratory has developed cell-permeant peptidic inhibitors targeting key interactions among the different NAD(P)H oxidase homologues. One of these inhibitors targeting nox2 and p47-phox interaction has proven useful in attenuating target neoplasia and hypertrophy. SUMMARY: Strategies aimed at specifically inhibiting NAD(P)H oxidase have proven effective in attenuating cardiovascular oxidative stress. The development of new inhibitors targeting novel oxidase homologues appears to hold significant promise for clarifying the physiologic role of these homologues as well as for the development of new antioxidant therapies.     

Direct detection of reactive oxygen species ex vivo

Oxidative stress is thought to play an important role in the initiation and progression of renal, cardiovascular, neoplastic, and neurodegenerative diseases. It is also widely believed that oxidative stress is a main cause of aging. Although considerable progress has been made in the understanding of the sources and actions of oxidative stress, the true role of oxygen-derived free radicals in the pathology of most human diseases largely remains to be determined. One major obstacle for radical research is the lack of specific and sensitive methods to quantify oxidative stress in vivo and in vitro. Although a multitude of different assays is available to assess free radical generation, each of these methods has substantial limitations. This article will provide a brief review on the most frequently used techniques to assess oxygen-derived free radical generation in isolated tissue preparations and cells. Emphasis will be put on most recent technical innovations and the shortcomings associated with current techniques.     

Comparative study on nephrotoxicity of ionic and non-ionic contrast agents for drip infused urography]

The effects on renal function of an ionic and hyperosmolaric contrast agent (diatrizoate) and a non-ionic and slightly hypertonic agent (iohexol) for drip infused urography were compared on 60 patients with normal renal function. Urine samples were collected before and 30 minutes after drip infusion of contrast agent, and analyzed for albumin (ALB), gamma-glutamyl transpeptidase (gamma-GTP), N-acetyl-beta-glucosaminidase (NAG), beta 2 microglobulin (beta 2MG) and creatinine (CRE). The urinary excretion of proteins and enzymes was compared with urinary CRE. gamma-GTP, NAG and beta 2MG increased significantly after infusion of diatrizoate. gamma-GTP and beta 2MG increased significantly after infusion of iohexol. Excretion of ALB, gamma-GTP, NAG and beta 2MG was significantly higher after infusion of diatrizoate than after iohexol. The urinary concentration of CRE was significantly lower after infusion of diatrizoate than after iohexol. The degree of renal damage after urography was no related to the appearance of allergy to the contrast agent or age of patient. Therefore, the non-ionic and slightly hyperosmolaric iohexol may be less toxic to the kidneys than the ionic and hypertonic diatrizoate. This nephrotoxicity after drip infused urography is thought to be related mainly to the osmolarity of contrast agent.     

Rosacea, reactive oxygen species, and azelaic Acid

Rosacea is a common skin condition thought to be primarily an inflammatory disorder. Neutrophils, in particular, have been implicated in the inflammation associated with rosacea and mediate many of their effects through the release of reactive oxygen species. Recently, the role of reactive oxygen species in the pathophysiology of rosacea has been recognized. Many effective agents for rosacea, including topical azelaic acid and topical metronidazole, have anti-inflammatory properties. in-vitro models have demonstrated the potent antioxidant effects of azelaic acid, providing a potential mechanistic explanation for its efficacy in the treatment of rosacea.     

皮肤光老化、活性氧簇与抗氧化剂

皮肤长期反复暴露于日光紫外线（UV）下可导致皮肤光老化.近年来研究表明活性氧簇（ROS）在UV致皮肤光老化过程中起重要作用.UV可在皮肤中诱生高浓度ROS,这些具有一个或多个未配对电子的原子或分子如不能被皮肤抗氧化系统及时清除则会和皮肤中的核酸、脂质、蛋白质等生物大分子发生化学反应,并影响相关细胞信号转导途径和基因表达,导致皮肤光老化发生,使用抗氧化剂清除ROS可能成为一种重要的光老化防治策略.     

Interaction of lidocaine with reactive oxygen and nitrogen species.

BACKGROUND AND OBJECTIVE: To investigate the ability of lidocaine to inhibit reactive oxygen and/or nitrogen species generation by either human leukocytes or cell-free systems via luminol- and lucigenin-enhanced chemiluminescence. METHODS: Venous blood was obtained from healthy volunteers and leukocytes were isolated, from which chemiluminescence was generated. Also, chemiluminescence, induced by H(2)O(2), HOCl, peroxynitrite or ferrous iron, was generated in cell-free systems. RESULTS: Lidocaine produced a concentration-dependent inhibition in chemiluminescence generated by leukocytes (92 +/- 1%, 1 mM). In cell-free experiments, lidocaine (1 mM) markedly inhibited chemiluminescence of xanthine-xanthine oxidase (24 +/- 3%), while it slightly suppressed hypochlorous acid-induced chemiluminescence (9 +/- 2%). Peroxynitrite-induced luminol- and lucigenin-enhanced chemiluminescence were also inhibited by lidocaine at 1 mM (19 +/- 3% and 48 +/- 8%, respectively). Lidocaine did not affect chemiluminescence generated by FeSO(4). However, lidocaine produced a biphasic effect on H(2)O(2)-induced chemiluminescence (37 +/- 5% inhibition at 0.01 mM and 61 +/- 17% activation at 1 mM). CONCLUSIONS: Lidocaine can elicit direct scavenging activity at high concentrations that might be important at or near the site of injection in local anaesthetic use.     

活性氧在骨性关节炎发病中的作用机制（英文）

近年来越来越多的研究表明活性氧在骨性关节炎的发病中起到关键作用,主要涉及到软骨细胞的凋亡和细胞外基质的退化,后者包括基质合成减少、分解增加以及钙化形成。本文就活性氧在骨性关节炎发病机制研究中的进展作一综述。     

Phosphate enhances reactive oxygen species production and suppresses osteoblastic differentiation

Phosphate has been shown to work as a signaling molecule in several cells including endothelial cells and chondrocytes. However, it is largely unknown how phosphate affects osteoblastic cells. In the present study, we investigated the effects of phosphate on reactive oxygen species (ROS) production and osteoblastic differentiation in murine osteoblastic MC3T3-E1 cells. Phosphate increased production of ROS in MC3T3-E1 cells and the inhibitors of sodium-phosphate cotransporter and NADPH oxidase suppressed ROS production by phosphate. Silencing Nox1 and Nox4 also inhibited the increase of ROS by phosphate. Phosphate also decreased alkaline phosphatase activity induced by bone morphogenetic protein 2 and this inhibition was abrogated by an inhibitor of NADPH oxidase. Furthermore, phosphate decreased the expression of osteoblastic marker genes in MC3T3-E1 cells. These results indicate that phosphate suppresses osteoblastic differentiation at least in part by enhancing ROS production in MC3T3-E1 cells.     

Gastrodin: An ancient Chinese herbal medicine as a source for anti-osteoporosis agents via reducing reactive oxygen species

Increased levels of reactive oxygen species (ROS) are a crucial pathogenic factor of osteoporosis. Gastrodin, isolated from the traditional Chinese herbal agent Gastrodia elata, is a potent antioxidant. We hypothesized that gastrodin demonstrates protective effects against osteoporosis by partially reducing reactive oxygen species in human bone marrow mesenchymal stem cells (hBMMSCs) and a macrophage cell line (RAW264.7 cells). We investigated gastrodin on osteogenic and adipogenic differentiation under oxidative stress in hBMMSCs. We also tested gastrodin on osteoclastic differentiation in RAW264.7 cells. Hydrogen peroxide (H₂O₂) was used to establish an oxidative cell injury model. Our results showed that gastrodin significantly promoted the proliferation of hBMMSCs, improved some osteogenic markers, reduced lipid generation and inhibited the mRNA expression of several adipogenic genes in hBMMSCs. Moreover, gastrodin reduced the number of osteoclasts, TRAP activity and the expression of osteoclast-specific genes in RAW264.7 cells. Gastrodin suppressed the production of reactive oxygen species in both hBMMSCs and RAW264.7 cells. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our data revealed that gastrodin treatment reduced the activity of serum bone degradation markers, such as CTX-1 and TRAP. Importantly, it ameliorated the micro-architecture of trabecular bones. Gastrodin decreased osteoclast numbers in vivo by TRAP staining. To conclude, these results indicated that gastrodin shows protective effects against osteoporosis linking to a reduction in reactive oxygen species, suggesting that gastrodin may be useful in the prevention and treatment of osteoporosis.     

Glomerular macrophages produce reactive oxygen species in experimental glomerulonephritis

The production of reactive oxygen species by intraglomerular macrophages was assessed in a macrophage dependent model of diffuse proliferative glomerulonephritis in rabbits. Glomerular macrophages were obtained from isolated nephritic glomeruli by short term (60 min) culture. Control macrophage populations were simultaneously obtained from peripheral blood (blood monocytes) and lung lavage fluid (alveolar macrophages). Superoxide anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical (OH.) production was assessed. Glomerular macrophage production of O2- (48.9 +/- 5.5 nmol/hr/10(6) cells), H2O2 (4.4 +/- 2.5 nmol/hr/10(6) cells) and OH. (57.8 +/- 4.7 U/hr/10(6) cells) was significantly greater than the production of reactive oxygen species seen with control monocyte populations: alveolar macrophages, O2- 9.8 +/- 2.0 nmol/hr/10(6) cells; H2O2 0.6 +/- 0.3 nmol/hr/10(6) cells; OH. 11.0 +/- 1.8 U/hr/10(6) cells; blood monocytes, O2- 8.6 +/- 1.4 nmol/hr/10(6) cells; OH. 9.9 +/- 1.2 U/hr/10(6) cells, (all P less than 0.05 cf. glom macs). Hydrogen peroxide production by blood monocytes (1.6 +/- 0.9 nmol/hr/10(6) cells) was less than glomerular macrophages, however this difference was not statistically significant. The enhanced production of reactive oxygen species by glomerular macrophages in this macrophage dependent model of glomerulonephritis suggests that these mononuclear cells are locally activated within the glomerulus following recruitment from the circulation. Reactive oxygen species production by glomerular macrophages may contribute to their ability to induce glomerular basement membrane injury in this disease.     

Generation of reactive oxygen species in subgroups of infertile men

The capacity to generate reactive oxygen species (ROS), both basally and after stimulation with the calcium ionophore A23187, was examined in the motile fraction of sperm isolated after swim-up from the semen of 10 naturally fertile men and three groups of infertile patients. The latter included: (1) men with a non-bacterial inflammation of the genital tract (n = 10); (2) men unable to impregnate their partners during an intra-uterine insemination programme (IUI) (n = 8) and their matched controls (n = 6); and (3) men with hypogonadotrophic hypogonadism (HH) who remained infertile after induction of spermatogenesis with gonadotrophin or gonadotrophin-releasing hormone therapy (n = 3) and their matched controls (n = 3). The levels of ROS production were elevated in the sperm of some infertile men with inflammation of the genital tract compared to those found in 10 naturally fertile men. In addition, sperm from those patients who remained infertile after an IUI programme produced higher amounts of ROS compared to their control group who became fertile. Similarly, the production of ROS by sperm from three patients with HH who remained infertile was significantly higher than those of the three men who became fertile. These data suggest that an excessive production of ROS by sperm may explain some cases of idiopathic male infertility.