Oxidative stress

About: Oxidative stress is a research topic. Over the lifetime, 86513 publications have been published within this topic receiving 3845790 citations. The topic is also known as: oxydative stress.

On the possible origins of DNA damage in human spermatozoa

Abstract: DNA damage in the male germ line has been linked with a variety of adverse clinical outcomes including impaired fertility, an increased incidence of miscarriage and an enhanced risk of disease in the offspring. The origins of this DNA damage could, in principle, involve: (i) abortive apoptosis initiated post meiotically when the ability to drive this process to completion is in decline (ii) unresolved strand breaks created during spermiogenesis to relieve the torsional stresses associated with chromatin remodelling and (iii) oxidative stress. In this article, we present a two-step hypothesis for the origins of DNA damage in human spermatozoa that highlights the significance of oxidative stress acting on vulnerable, poorly protaminated cells generated as a result of defective spermiogenesis. We further propose that these defective cells are characterized by several hallmarks of 'dysmaturity' including the retention of excess residual cytoplasm, persistent nuclear histones, poor zona binding and disrupted chaperone content. The oxidative stress experienced by these cells may originate from infiltrating leukocytes or, possibly, the entry of spermatozoa into an apoptosis-like cascade characterized by the mitochondrial generation of reactive oxygen species. This oxidative stress may be exacerbated by a decline in local antioxidant protection, particularly during epididymal maturation. Finally, if oxidative stress is a major cause of sperm DNA damage then antioxidants should have an important therapeutic role to play in the clinical management of male infertility. Carefully controlled studies are now needed to critically examine this possibility.

Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats.

Abstract: Omega-3 fatty acids (i.e., docosahexaenoic acid; DHA) regulate signal transduction and gene expression, and protect neurons from death. In this study we examined the capacity of dietary omega- 3 fatty acids supplementation to help the brain to cope with the effects of traumatic injury. Rats were fed a regular diet or an experimental diet supplemented with omega-3 fatty acids, for 4 weeks before a mild fluid percussion injury (FPI) was performed. FPI increased oxidative stress, and impaired learning ability in the Morris water maze. This type of lesion also reduced levels of brainderived neurotrophic factor (BDNF), synapsin I, and cAMP responsive element-binding protein (CREB). It is known that BDNF facilitates synaptic transmission and learning ability by modulating synapsin I and CREB. Supplementation of omega-3 fatty acids in the diet counteracted all of the studied effects of FPI, that is, normalized levels of BDNF and associated synapsin I and CREB, reduced oxidative damage, and counteracted learning ...

Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells.

Abstract: Mitochondrial respiratory function is impaired in the target tissues of patients with mitochondrial diseases and declines with age in various human tissues It is generally accepted that respiratory-chain defects result in enhanced production of reactive oxygen species and free radicals in mitochondria Recently, we have demonstrated that the copy number of mitochondrial DNA (mtDNA) is increased in the lung tissues of elderly human subjects The mtDNA copy number was suggested to be increased by a feedback mechanism that compensates for defects in mitochondria harbouring mutated mtDNA and a defective respiratory system However, the detailed mechanism remains unclear In this study, we treated a human lung fibroblast cell line, MRC-5, with H(2)O(2) at concentrations of 90-360 microM After the treatment for 24-72 h, we found that cells were arrested at G(0) and G(1) phases but that mitochondrial mass and mtDNA content were significantly increased in a concentration- and time-dependent manner Moreover, the oxidative stress induced by buthionine sulphoximine was also found to cause an increase in mitochondrial mass of the treated cells Increased uptake of a vital mitochondrial dye Rhodamine 123 and enhanced tetrazolium [MTT, 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] reduction revealed that the mitochondria increased by H(2)O(2) treatment were functional In addition, the increase in the mitochondrial mass was also observed in cell-cycle-arrested cells induced by mimosine, lovastatin and genistein Taken together, these findings suggest that the increase in mitochondrial mass and mtDNA content are the early molecular events of human cells in response to endogenous or exogenous oxidative stress through cell-cycle arrest

Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes.

Abstract: Hyperglycemia causes many of the pathological consequences of both type 1 and type 2 diabetes. Much of this damage is suggested to be a consequence of elevated production of reactive oxygen species by the mitochondrial respiratory chain during hyperglycemia. Mitochondrial radical production associated with hyperglycemia will also disrupt glucose-stimulated insulin secretion by pancreatic beta-cells, because pancreatic beta-cells are particularly susceptible to oxidative damage. Therefore, mitochondrial radical production in response to hyperglycemia contributes to both the progression and pathological complications of diabetes. Consequently, strategies to decrease mitochondrial radical production and oxidative damage may have therapeutic potential. This could be achieved by the use of antioxidants or by decreasing the mitochondrial membrane potential. Here, we outline the background to these strategies and discuss how antioxidants targeted to mitochondria, or selective mitochondrial uncoupling, may be potential therapies for diabetes.