Oxidative stress in otosclerosis

Objectives: Otosclerosis is a disease involving abnormal bone turnover in the human otic capsule that results in hearing loss. Several hypotheses have been suggested for the etiopathogenesis of otosclerosis; however, its etiology remains unclear.

Methods: This study evaluated the correlation between otosclerosis and levels of paraoxonase-1 (PON1), arylesterase, total antioxidant status, total oxidant status (TOS), oxidative stress index (OSI), total sulfhydryl (-SH) groups, lipid hydroperoxide, and ceruloplasmin in the serum of otosclerosis patients and healthy subjects with respect to oxidative stress.

Results: In our study, TOS and OSI levels were higher in the otosclerosis patients than in the controls. The PON1 levels showed that oxidative stress was severe, and as a result, antioxidants were consumed and depleted.

Discussion: When an imbalance between oxygen free radical production and antioxidative defense mechanisms occurs, reactive oxygen species levels may increase, which in turn may damage cells and tissues through the peroxidation of phospholipid membrane structures. The body initially responds with increased antioxidant production, but if the oxidative stress is severe, decreased antioxidant levels may result. This study reports expression levels of oxidative stress species in otosclerosis patients.     

Oxidative stress in mature rat testis and its developmental changes

Active oxygen causes various problems including male infertility through the oxidation of DNA, proteins, and lipids. In the present study, we examined the immunohistochemical localization of molecules involved in oxidative stress including 8-hydroxy-2-deoxyguanosine (8-OHdG), superoxide dismutase (SOD), and protein disulfide isomerase (PDI) in mature and developing rat testes. In mature rat testes, 8-OHdG was detected in leptotene, zygotene, and early pachytene spermatocytes, while its expression was weak in late pachytene stage spermatocytes. On the other hand, SOD was detected in late pachytene spermatocytes but not in early pachytene and former spermatocytes, suggesting the efficient removal of active oxygen by SOD in late pachytene spermatocytes. In developing rat testes, 8-OHdG expression peaked at 4 weeks when spermatocytes started to differentiate to the late pachytene stage, while SOD started to be expressed at 4 weeks after birth. These findings suggest that the defense system against oxidative stress by SOD is developed in late pachytene stage spermatocytes at 4 weeks after birth. The present findings aid our understanding of the defensive mechanism against oxidative stress in developing and mature testes.     

DNA oxidation and superoxide dismutase in the kidney of diabetic animals: effects of pioglitazone and repaglinide

In the present study, DNA oxidative damage was elevated and superoxide dismutase (Cu,Zn-SOD) metabolism was disturbed in the kidney of alloxan-induced diabetic animals. The effects of pioglitazone and repaglinide, new oral antidiabetics, on 8-hydroxy-2′-deoxyguanosine (8-OHdG) and Cu,Zn-SOD were studied. Diabetic versus control levels (mean ± SE) of 8-OHdG were 24.9 ± 0.2 vs. 21.8 ± 0.1 and 21.5 ± 0.2 vs 20.1 ± 0.2 pmol/μg DNA after 4 and 8 weeks, respectively. At p<0.05, pioglitazone diminished this parameter in diabetic animals (22.0 ± 0.2 and 20.1 ± 0.3 pmol/μg DNA). The level was not affected in diabetic groups receiving repaglinide (24.9 ± 0.2 and 21.5 ± 0.3 pmol/μg DNA). In diabetic kidney, Cu,Zn-SOD mRNA was diminished relative to control animals and was modulated by pioglitazone and repaglinide treatments. Simultaneously, Cu,Zn-SOD activity was also diminished (1.5 ± 0.2 vs. 2.8 ± 0.3 and 1.8 ± 0.1 vs 2.9 ± 0.3 U/mg protein after 4 and 8 weeks, respectively) and partly changed after pioglitazone (2.1 ± 0.4 and 2.3 ± 0.3 U/mg protein) and repaglinide (2.0 ± 0.1 and 2.4 ± 0.2 U/mg protein). These results suggest that a reduction in oxidative stress in diabetic kidney can be achieved with the administration of pioglitazone and to some extent using repaglinide treatment.     

Oxidative stress and eicosanoids in the kidneys of hyperglycemic rats treated with dehydroepiandrosterone

Oxidative stress plays a crucial role in the pathogenesis of chronic diabetic complications. Normoglycemic and streptozotocin-diabetic rats were treated with dehydroepiandrosterone (DHEA) (4 mg/d per rat) for 3 weeks. At the end of treatment, hydroxynonenal, hydroperoxyeicosatetraenoic acids and antioxidant levels, as well as Na/K-ATPase activity and membrane fatty acids composition were evaluated in kidney homogenates. Chronic hyperglycemia caused a marked increase of both hydroxynonenal and lipoxygenase pathway products and a drop in both GSH levels and membrane Na/K-ATPase activity. DHEA treatment restored the antioxidant levels to close to the control value and considerably reduced hydroxynonenal and hydroperoxyeicosatetraenoic acid levels. Moreover, DHEA counteracted the detrimental effect of hyperglycemia on membrane function: the drop of Na/K-ATPase activity in diabetic animals was significantly inhibited by DHEA treatment. These results show that DHEA reduces oxidative stress and the consequent increase of lipoxygenase pathway products induced by experimental diabetes in rat kidney; they also suggest that, by reducing the inflammatory response to oxidative stress, DHEA treatment might delay the progression of diabetic kidney disease.     

Oxidative stress in the placenta

Pregnancy is a state of oxidative stress arising from increased placental mitochondrial activity and production of reactive oxygen species (ROS), mainly superoxide anion. The placenta also produces other ROS including nitric oxide, carbon monoxide, and peroxynitrite which have pronounced effects on placental function including trophoblast proliferation and differentiation and vascular reactivity. Excessive production of ROS may occur at certain windows in placental development and in pathologic pregnancies, such as those complicated by preeclampsia and/or IUGR, overpowering antioxidant defenses with deleterious outcome. In the first trimester, establishment of blood flow into the intervillous space is associated with a burst of oxidative stress. The inability to mount an effective antioxidant defense against this results in early pregnancy loss. In late gestation increased oxidative stress is seen in pregnancies complicated by diabetes, IUGR, and preeclampsia in association with increased trophoblast apoptosis and deportation and altered placental vascular reactivity. Evidence for this oxidative stress includes increased lipid peroxides and isoprostanes and decreased expression and activity of antioxidants. The interaction of nitric oxide and superoxide produces peroxynitrite, a powerful prooxidant with diverse deleterious effects including nitration of tyrosine residues on proteins thus altering function. Nitrative stress, subsequent to oxidative stress is seen in the placenta in preeclampsia and diabetes in association with altered placental function.     

Increased oxidative stress during hyperglycemic cerebral ischemia

In this review, we summarize the role of hyperglycemia during cerebral ischemia. Hyperglycemia occurring during experimental and clinical stroke has been associated with increased cerebral damage. Increased oxidative stress resulting from hyperglycemia is believed to contribute to the exacerbated damage. More specifically, superoxide, nitric oxide and peroxynitrite are believed to play an important role in cerebral damage. This also involves increased recruitment of various blood cells to the ischemic zone that contribute to inflammation. We present data from our group and others that demonstrate that free radical production is increased during hyperglycemic stroke in rodents. Recent data suggest that inflammation is an important component of ischemic damage under both normo- and hyperglycemic conditions. We summarize numerous studies that indicate that a variety of antioxidant (inhibition of free radical production, scavenging of free radicals and increasing free radical degradation) and anti-inflammatory strategies decrease cerebral infarction. Finally, we compare the success of some of these strategies in clinical trials compared to the animal models.     

Oxidative and nitrative stress markers in glaucoma

Glaucoma is a progressive optic neuropathy and is the leading cause of blindness in the United States and other industrialized countries. Elevated pressure in the eye is a risk factor for glaucoma and indeed experimental studies of induced pressure elevation in nonhuman primate's results in typical glaucomatous optic nerve damage. However, normal intraocular pressure can also lead to loss of vision in glaucoma. Although the initiating causes leading to glaucoma are unknown, oxidative and nitrative stress appears to play a role in the progressive neuronal death that is characteristic of glaucomatous optic nerve damage. Increased markers of oxidative stress that have been reported in glaucoma include protein nitrotyrosine, carbonyls in proteins, lipid oxidation products and oxidized DNA bases. Studies have also highlighted the role of nitric oxide in glaucoma by reporting the presence of inducible nitric oxide synthase in the iris-ciliary body, retina and in the glaucomatous optic nerve head of experimental rat models. This review discusses the role of reactive oxygen and nitrogen species in the pathogenesis of glaucoma and examines the relevance of antioxidants in neurodegeneration associated with the disease. It is concluded that oxidative and nitrative stress have a pathogenic role in glaucoma.     

Oxidative stress in industrial fungi

Fungi are amongst the most industrially important microorganisms in current use within the biotechnology industry. Most such fungal cultures are highly aerobic in nature, a character that has been frequently referred to in both reactor design and fungal physiology. The most fundamentally significant outcome of the highly aerobic growth environment in fermenter vessels is the need for the fungal culture to effectively combat in the intracellular environment the negative consequences of high oxygen transfer rates. The use of oxygen as the respiratory substrate is frequently reported to lead to the development of oxidative stress, mainly due to oxygen-derived free radicals, which are collectively termed as reactive oxygen species (ROS). Recently, there has been extensive research on the occurrence, extent, and consequences of oxidative stress in microorganisms, and the underlying mechanisms through which cells prevent and repair the damage caused by ROS. In the present study, we critically review the current understanding of oxidative stress events in industrially relevant fungi. The review first describes the current state of knowledge of ROS concisely, and then the various antioxidant strategies employed by fungal cells to counteract the deleterious effects, together with their implications in fungal bioprocessing are also discussed. Finally, some recommendations for further research are made.     

Oxidative stress and antioxidant strategies in dermatology

Oxidative stress results from a prooxidant-antioxidant imbalance, leading to cellular damage. It is mediated by free radicals, such as reactive oxygen species or reactive nitrogen species, that are generated during physiological aerobic metabolism and pathological inflammatory processes. Skin serves as a protective organ that plays an important role in defending both external and internal toxic stimuli and maintaining homeostasis. It is becoming increasingly evident that oxidative stress is involved in numerous skin diseases and that antioxidative strategies can serve as effective and easy methods for improving these conditions. Herein, we review dysregulated antioxidant systems and antioxidative therapeutic strategies in dermatology.     

Oxidative stress and apoptosis in preeclampsia

We aimed to determine the oxidative stress and antioxidant status in preeclamptic placenta. Also, we investigated the apoptotic index of villous trophoblast and proliferation index of cytotrophoblasts. The study included 32 pregnant with preeclampsia and 31 normotensive healthy pregnant women. Malondialdehyde (MDA) and total antioxidant status (TAS) levels were measured in the placenta. For detection of apoptosis and proliferation in trophoblast, apoptosis protease activating factor 1 (APAF-1) and Ki-67 were used. Placental MDA levels in preeclamptic women were significantly higher than normal pregnancies (p = 0.002). There was no significant difference between the groups in the TAS levels of placenta (p = 0.773). Also, the apoptotic index in villous trophoblasts increased (p < 0.001), but proliferation index did not change in preeclampsia (p = 0.850). Increased oxidative stress and apoptosis in pathological placenta are not balanced by antioxidant systems and proliferation mechanisms.     

Endoplasmic reticulum stress and Oxidative stress in the pathogenesis of Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. The underlying causes of the disease progression in NAFLD are unclear. Recent evidences suggest endoplasmic reticulum stress in the development of lipid droplets (steatosis) and subsequent generation of reactive oxygen species (ROS) in the progression to non-alcoholic steatohepatitis (NASH). The signalling pathway activated by disruption of endoplasmic reticulum (ER) homoeostasis, called as unfolded protein response, is linked with membrane biosynthesis, insulin action, inflammation and apoptosis. ROS are important mediators of inflammation. Protein folding in ER is linked to ROS. Therefore understanding the basic mechanisms that lead to ER stress and ROS in NAFLD have become the topics of immense interest. The present review focuses on the role of ER stress and ROS in the pathogenesis of NAFLD. We also highlight the cross talk between ER stress and oxidative stress which suggest and encourage the development of therapeutics for NAFLD. Further we have reviewed various strategies used for the management of NAFLD/NASH and limitations of such strategies. Our review therefore highlights the need for newer strategies with regards to ER stress and oxidative stress.     

姜黄素及其类似物J7对2型糖尿病大鼠睾丸氧化应激损伤的干预作用*

目的: 研究姜黄素(CUR)及其类似物J7对糖尿病大鼠睾丸氧化应激损伤的干预作用。方法: 60只SD大鼠随机分组,其中10只作为正常(NC)组,余50只通过高脂饮食和腹腔注射链脲佐菌素诱导建立糖尿病大鼠模型,造模成功后将其再分为4组:糖尿病(DM,n=12)组、姜黄素治疗(CUR,n=10)组、J7高剂量治疗(J+,n=10)组、J7低剂量治疗(J-,n=10)组。CUR组大鼠每天予以姜黄素20 mg/kg灌胃治疗,J+及J-组分别予以J7 20 mg/kg、10 mg/kg灌胃治疗,8周后处死大鼠,测量各组大鼠体重、空腹血糖,羟胺法和硫代巴比妥酸法分别检测超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,Western blot法检测tNrf2、pNrf2、CAT、NQO1蛋白表达水平,qRT-PCR检测CAT、NQO1、HO1 mRNA表达水平,光镜下观察大鼠睾丸形态学改变,免疫组化检测Nrf2及CAT蛋白表达情况。结果: DM组血糖、MDA水平升高(P＜0.05),体重、SOD活性、pNrf2/tNrf2、CAT、NQO1蛋白及CAT、NQO1、HO1 mRNA水平均有下降(P＜0.05);光镜下见睾丸各级生精细胞减少、排列紊乱;免疫组化显示Nrf2蛋白核周表达量下降,CAT蛋白表达水平降低。经姜黄素及J7治疗后,三个治疗组的MDA水平均下降(P＜0.05),SOD活性、pNrf2/tNrf2、CAT、NQO1蛋白及NQO1、HO1 mRNA水平均上升(P＜0.05),J+及J-组血糖显著下降(P＜0.05),J+组CAT mRNA水平显著上升(P＜0.05);J+组pNrf2/tNrf2比值明显高于CUR组及J-组(P＜0.05),J+组CAT蛋白水平也明显高于J-组(P＜0.05),其余指标在三个治疗组间不具有显著性差异。光镜下见三个治疗组睾丸形态学病变减轻;免疫组化显示Nrf2蛋白核周表达量上升,CAT蛋白表达水平升高。提示高剂量J7抗糖尿病大鼠睾丸的氧化应激损伤的能力较强。结论: 姜黄素及J7可在一定程度上对抗糖尿病大鼠睾丸的氧化应激损伤,其机制可能与Nrf2-ARE信号通路的激活相关。     

Oxidative stress, osmotic stress and apoptosis: impacts on sperm function and preservation in the horse

Oxidative stress is an important component of the cytopathology of equine spermatozoa undergoing storage as liquid or frozen semen. Damage to chromatin, membranes and proteins of sperm are important components of oxidative damage to sperm. Similarly, sperm are exposed to a variety of osmotic stresses during storage that result from exposure to hypertonic media or result as a consequence of osmotic changes induced during freezing. A number of changes induced during processing and storage of equine sperm also appear to induce apoptotic-like changes which may adversely affect sperm survival and function. These processes appear in many cases to be interrelated, and this review will examine current understanding of these processes on the equine sperm function.     

Expression of stress inducible protein 1 (Stip1) in the mouse testis

Phthalate esters are considered endocrine disruptors that interfere with the endocrine balance and development of the mammalian testis. Mono-2-ethylhexyl phthalate (MEHP), the active metabolite of the ubiquitously used plasticizer di-2-ethylhexyl phthalate (DEHP), acts upon Sertoli cells as initial target. By subtractive cDNA libraries we identified genes deregulated as response to MEHP in primary cultures of mouse Sertoli cells. The expression of mouse stress inducible protein 1 (Stip1) was detected as upregulated as a result of MEHP exposure. Stip1 is a cochaperone protein that is homologous to the human heat shock cognate protein 70 (hsc70)/heat shock protein 90 (hsp90)-organizing protein (Hop). To assess the presence and localization of Stip1 in mouse testis and its potential role in stress defense, we studied the expression pattern of the Stip1 protein by immunohistochemistry and of the mRNA by in situ hybridization. Both the protein and the mRNA of Stip1 were mainly found in the cytoplasm of all types of spermatogonia and spermatocytes up till zygotene, the expression decreased during late pachytene and was very weak in diplotene spermatocytes and round spermatids. Interestingly, this expression pattern resembled the pattern of stress sensitivity of spermatogenic cells in that the most sensitive cell types show the weakest expression of Stip1. This suggests an important role for Stip1 in the ability of germ cells to survive in stress conditions including high temperatures.     

Oxidative stress in the rat heart,studies on low-level chemiluminescence

Detection of ultraweak chemiluminescence (CL) emission from the surface of the organ is a sensitive and non-disruptive tool to evaluate the oxidative stress in rat heart. Indeed, an increased photon emission rate can be observed when cellular antioxidants such as glutathione or vitamin E are depleted, or when organic hydroperoxides are infused. We used CL recording to demonstrate in rat heart that: (i) different diets may lead to different heart sensitivity to an oxidative stress; and (ii) post-ischaemic reoxygenation induces an oxidative stress. CL emission induced by an oxidative stress is accompanied by an increased release of eicosanoids. However, while non-steroid anti-inflammatory drugs (aspirin, indomethacin and ibuprofen) prevented eicosanoid release, these compounds dramatically enhanced hydroperoxide-dependent CL. The nature of this phenomenon is still obscure, but the increase of steady-state concentration of excited species caused by anti-inflammatory drugs seems to be pathophysiologically relevant, since in all our experimental conditions tissue damage was proportional to CL emission rate.     

Oxidative stress and antioxidant defenses in pregnant women

Abstract

Objectives

Oxidative stress (OS) is defined as an imbalance in the production of reactive oxygen species and the capacity of antioxidant defenses. The objective of this work was to investigate OS and antioxidant capacity in pregnant women.

Methods

Parameters of the oxidative status and antioxidant capacity in serum and whole blood were evaluated in thirty-nine women with normal pregnancy.

Results

The assessment of antioxidants indicated an increase in superoxide dismutase and catalase activities (P < 0.05 and P < 0.01) and a decrease in ascorbic acid levels and the total content of sulfhydryl (P < 0.05 and P < 0.001). Additionally, when the pro-oxidant system was investigated we found an increase (P < 0.01) in malondialdehyde and no significant change (P > 0.05) in protein carbonylation.

Discussion

This study demonstrates that there is a change in the pro-oxidant and antioxidant defenses associated with body and circulation changes that are inherent to the pregnancy process.     

Oxidative stress alters global histone modification and DNA methylation

The JmjC domain-containing histone demethylases can remove histone lysine methylation and thereby regulate gene expression. The JmjC domain uses iron Fe(II) and α-ketoglutarate (αKG) as cofactors in an oxidative demethylation reaction via hydroxymethyl lysine. We hypothesize that reactive oxygen species will oxidize Fe(II) to Fe(III), thereby attenuating the activity of JmjC domain-containing histone demethylases. To minimize secondary responses from cells, extremely short periods of oxidative stress (3 h) were used to investigate this question. Cells that were exposed to hydrogen peroxide (H₂O₂) for 3 h exhibited increases in several histone methylation marks including H3K4me3 and decreases of histone acetylation marks including H3K9ac and H4K8ac; preincubation with ascorbate attenuated these changes. The oxidative stress level was measured by generation of 2′,7′-dichlorofluorescein, GSH/GSSG ratio, and protein carbonyl content. A cell-free system indicated that H₂O₂ inhibited histone demethylase activity where increased Fe(II) rescued this inhibition. TET protein showed a decreased activity under oxidative stress. Cells exposed to a low-dose and long-term (3 weeks) oxidative stress also showed increased global levels of H3K4me3 and H3K27me3. However, these global methylation changes did not persist after washout. The cells exposed to short-term oxidative stress also appeared to have higher activity of class I/II histone deacetylase (HDAC) but not class III HDAC. In conclusion, we have found that oxidative stress transiently alters the epigenetic program process through modulating the activity of enzymes responsible for demethylation and deacetylation of histones.     

Modification of cardiac oxidative stress in alloxan-induced diabetic rabbits with repaglinide treatment

The aim of this study was to analyze the antioxidative effect of repaglinide in the heart of alloxan-induced diabetic rabbits. The activities of superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione (GSH), ascorbic acid (AA), products of lipid peroxidation (LPO) and protein carbonyl groups (PCG) were estimated after 4 and 8 weeks of repaglinide treatment (1 mg daily). At significance level p<0.05, in diabetic heart the activities of Cu,Zn-SOD and CAT were elevated as compared to control values (by 60.7% and 55.3% for Cu,Zn-SOD, and by 89.7% and 77.4% for CAT after 4 and 8 weeks, respectively). The level of AA was diminished by 52.5% and 41.5% while GSH-Px and GSSG-R activities were decreased after 4 weeks of experiment (by 11.5% and 14.4%, respectively). GSH level was diminished by 33.2% after 8 weeks. Simultaneously, in diabetic heart the levels of LPO and PCG were elevated as compared to control values (by 51.6% and 111.3% for LPO, and by 72.0% and 132.9% for PCG after 4 and 8 weeks, respectively). In diabetic animals, repaglinide normalized GSH-Px activity and GSH level. It modified the activities of Cu,Zn-SOD, CAT and AA as compared to diabetic non-treated animals. In diabetic-treated rabbits the level of LPO was diminished as compared to diabetic non-treated animals, while the level of PCG was not affected. In the present study, repaglinide did not affect blood glucose and plasma insulin concentrations in diabetic rabbits. Nevertheless, the drug showed some beneficial antioxidative properties in the heart tissue.