Evaluation of the Oxidative Effect of Long-Term Repetitive Hyperbaric Oxygen Exposures on Different Brain Regions of Rats

Hyperbaric oxygen (HBO2) exposure affects both oxidative and antioxidant systems. This effect is positively correlated with the exposure time and duration of the treatment. The present study aims enlightening the relation of HBO2 with oxidative/antioxidant systems when administered in a prolonged and repetitive manner in brain tissues of rats. Sixty rats were divided into 6 study (n = 8 for each) and 1 control (n = 12) group. Rats in the study groups were daily exposed 90-min HBO2 sessions at 2.8 ATA for 5, 10, 15, 20, 30 and 40 days. One day after the last session, animals were sacrificed; their whole brain tissue was harvested and dissected into three different regions as the outer grey matter (cortex), the inner white matter and cerebellum. Levels of lipid peroxidation and protein oxidation and activities of superoxide dismutase and glutathione peroxidase were measured in these tissues. Malondialdehyde, carbonylated protein and glutathione peroxidase levels were found to be insignificantly increased at different time-points in the cerebral cortex, inner white matter and cerebellum, respectively. These comparable results provide evidence for the safety of HBO treatments and/or successful adaptive mechanisms at least in the brain tissue of rats, even when administered for longer periods

Ozone Therapy and Hyperbaric Oxygen Treatment in Lung Injury in Septic Rats

Various therapeutic protocols were used for the management of sepsis including hyperbaric oxygen (HBO) therapy. It has been shown that ozone therapy (OT) reduced inflammation in several entities and exhibits some similarity with HBO in regard to mechanisms of action. We designed a study to evaluate the efficacy of OT in an experimental rat model of sepsis to compare with HBO. Male Wistar rats were divided into sham, sepsis+cefepime, sepsis+cefepime+HBO, and sepsis+cefepime+OT groups. Sepsis was induced by an intraperitoneal injection of Escherichia coli; HBO was administered twice daily; OT was set as intraperitoneal injections once a day. The treatments were continued for 5 days after the induction of sepsis. At the end of experiment, the lung tissues and blood samples were harvested for biochemical and histological analysis. Myeloperoxidase activities and oxidative stress parameters, and serum proinflammatory cytokine levels, IL-1β and TNF-α, were found to be ameliorated by the adjuvant use of HBO and OT in the lung tissue when compared with the antibiotherapy only group. Histologic evaluation of the lung tissue samples confirmed the biochemical outcome. Our data presented that both HBO and OT reduced inflammation and injury in the septic rats' lungs; a greater benefit was obtained for OT. The current study demonstrated that the administration of OT as well as HBO as adjuvant therapy may support antibiotherapy in protecting the lung against septic injury. HBO and OT reduced tissue oxidative stress, regulated the systemic inflammatory response, and abated cellular infiltration to the lung demonstrated by findings of MPO activity and histopathologic examination. These findings indicated that OT tended to be more effective than HBO, in particular regarding serum IL-1β, lung GSH-Px and histologic outcome

Epigenetic perturbations in the pathogenesis of mustard toxicity; hypothesis and preliminary results

Among the most readily available chemical warfare agents, sulfur mustard (SM), also known as mustard gas, has been the most widely used chemical weapon. SM causes debilitating effects that can leave an exposed individual incapacitated for days to months; therefore delayed SM toxicity is of much greater importance than its ability to cause lethality. Although not fully understood, acute toxicity of SM is related to reactive oxygen and nitrogen species, oxidative stress, DNA damage, poly(ADP-ribose) polymerase (PARP) activation and energy depletion within the affected cell. Therefore several antioxidants and PARP inhibitors show beneficial effects against acute SM toxicity. The delayed toxicity of SM however, currently has no clear mechanistic explanation. One third of the 100,000 Iranian casualties are still suffering from the detrimental effects of SM in spite of the extensive treatment. We, therefore, made an attempt whether epigenetic aberrations may contribute to pathogenesis of mustard poisoning. Preliminary evidence reveals that mechlorethamine (a nitrogen mustard derivative) exposure may not only cause oxidative stress, DNA damage, but epigenetic perturbations as well. Epigenetic refers to the study of changes that influence the phenotype without causing alteration of the genotype. It involves changes in the properties of a cell that are inherited but do not involve a change in DNA sequence. It is now known that in addition to mutations, epimutations contribute to a variety of human diseases. Under light of preliminary results, the current hypothesis will focus on epigenetic regulations to clarify mustard toxicity and the use of drugs to correct possible epigenetic defects

Molecular, genetic and epigenetic pathways of peroxynitrite-induced cellular toxicity

Oxidative stress plays a key role in the pathogenesis of cancer and many metabolic diseases; therefore, an effective antioxidant therapy would be of great importance in these circumstances. Nevertheless, convincing randomized clinical trials revealed that antioxidant supplementations were not associated with significant reduction in incidence of cancer, chronic diseases and all-cause mortality. As oxidation of essential molecules continues, it turns to nitro-oxidative stress because of the involvement of nitric oxide in pathogenesis processes. Peroxynitrite damages via several distinctive mechanisms; first, it has direct toxic effects on all biomolecules and causes lipid peroxidation, protein oxidation and DNA damage. The second mechanism involves the induction of several transcription factors leading to cytokine-induced chronic inflammation. Finally, it causes epigenetic perturbations that exaggerate nuclear factor kappa-B mediated inflammatory gene expression. Lessons-learned from the treatment of several chronic disorders including pulmonary diseases suggest that, chronic inflammation and glucocorticoid resistance are regulated by prolonged peroxynitrite production

The oxidative and morphological effects of high concentration chronic toluene exposure on rat sciatic nerves

This study was designed to investigate the effects of chronic toluene inhalation in high concentration on lipid peroxidation, antioxidant enzyme activities and ultrastructural changes in the sciatic nerves of rats. Male Wistar albino rats (150-250 g) were divided in two experimental groups: the control and the toluene treated group (n=10 for each). Toluene treatment was performed by inhalation of 3000 ppm toluene, in a 8 h/day and 6 day/week order for 16 weeks. Blood and tissue samples were obtained for biochemical and histopathological investigation. The blood and sciatic nerves were assayed for toluene by gas chromatography. Toluene significantly increased blood and tissue malondialdehyde (MDA), and decreased tissue superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but not tissue catalase (CAT) levels when compared with controls. Electron micrographs of sciatic nerve in the toluene group shows myelin destructions with onion-bulb and bubble form protrusion on the myelin sheath and axolemma border of myelinated axons. The area of injury on the myelin sheath were measured by Image-Pro Plus. Mean of the injury area were estimated 34% each myelin. These findings indicate that chronic toluene inhalation might be involved with free radical processes

Melatonin and Melatonergic Drugs in Clinical Practice

XVII, 402 p. 46 illus., 19 illus. in color.onlin

The Similarity Between Aspirin Treatment and the Lack of Response to Epinephrine and the Frequency of Aspirin Resistance in Healthy Males

6th National Congress of Thrombosis, Haemostasis and Angiology -- MAY 05-07, 2006 -- Izmir, TURKEYWOS: 000288463500012PubMed ID: 20460337Objectives: The lack of response of platelets against epinephrine has been discovered with a frequency of 14% to 40% in previous studies. There are studies that have demonstrated the effect of aspirin on platelets may resemble the lack of response to epinephrine. In this study, the extent of the effects of aspirin treatment on aggregation and secretion in healthy males with a lack of response to epinephrine and the frequency of aspirin resistance were investigated. Methods: Blood samples were collected at the beginning and at the end of a 10-day aspirin usage in 52 healthy males. Epinephrine, adenosine diphosphate (ADP), collagen, arachidonic acid (AA) and thrombin aggregations, and adenosine triphosphate (ATP) secretion were studied. Participants were assigned to nonresponder ( 60%) groups, depending on their maximum aggregation responses to epinephrine. Participants who displayed an aggregation to AA at the end of the aspirin treatment were accepted to be aspirin resistant. Results: Of the 52 participants, 4 were found to be nonresponders and 3 of 52 of the participants were found to be semiresponders. Although the lack of response to epinephrine and aspirin treatment displayed similarities in aggregations using epinephrine, ADP, collagen, and thrombin, they differed in aggregations using AA and for ATP secretion. The ratio of aspirin resistance was determined to be 4:52. Conclusions: The observation of AA aggregation in the participants with a lack of response to epinephrine demonstrates that epinephrine nonresponse cannot substitute aspirin treatment. The fact that aspirin resistance is observed in healthy males supports the view that aspirin resistance exists even before the first usage