Oxidative Stress and Reproduction Health: Physiology, Pathology, and Clinical Biomarkers

Reactive oxygen species (ROS) are free radicals derived from oxygen during normal cellular metabolism. Cells, under aerobic conditions, have a defense system against ROS, and in normal circumstances, there is an appropriate balance between prooxidants and antioxidants. When an overproduction of ROS develops or the body fails to eliminate ROS in excess, oxidative stress arises, during which ROS accumulate and damage cells and tissues. ROS plays a crucial role in the physiological processes and signaling pathways associated in both male and female fertility. In females, oxidative stress acts as a mediator in the modulation of important ovarian functions, and its complications such as abortions, recurrent pregnancy losses, preeclampsia, and gestational diabetes. In males, ROS plays an important role in normal physiological processes such as capacitation, hyperactivation, acrosome reaction, and sperm-oocyte fusion to ensure appropriate fertilization. However, high concentrations of ROS cause sperm pathologies (ATP depletion) in the form of inadequate axonemal phosphorylation or lipid peroxidation, resulting in a loss of sperm motility and viability. This chapter will highlight the mechanisms, production, physiological, and pathophysiological roles of ROS in relation to the male and female reproductive system, and recent advances in diagnostic methods that use ROS as biochemical markers

Dietary Regulation of Keap1/Nrf2/ARE Pathway: Focus on Acai Berries and Pistachios and Cashews as Natural Food Sources

Inflammation is a biological reaction to oxidative stress in which cell starts producing proteins, enzymes, and other substances to restore homeostasis, while oxidative stress could be intrinsically a biochemical imbalance of the physiologically redox status of the intracellular environment. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway, which controls the transcription of numerous antioxidant genes that protect cellular homeostasis and detoxification genes that process and eliminate all toxic compounds and substances before they can cause damage. The Nrf2 pathway is the heart of the daily biological response to oxidative stress. Transient activation of Nrf2 by diet can upregulate antioxidant enzymes to protect cells against oxidative stress inducers. In this chapter, we summarize the effects of some novel foods in the regulation of the Nrf2/ARE pathway and its cellular mechanisms

Editorial: Non-invasive brain stimulation techniques in neurological and neuropsychiatric disorders: Physiological and molecular evidence

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Neuroprotective Effect of Artesunate in Experimental Model of Traumatic Brain Injury

Traumatic brain injuries (TBI) are an important public health challenge. In addition, subsequent events at TBI can compromise the quality of life of these patients. In fact, TBI is associated with several complications for both long and short term, some evidence shows how TBI is associated with a decline in cognitive functions such as the risk of developing dementia, cerebral atrophy, and Parkinson disease. After the direct damage from TBI, a key role in TBI injury is played by the inflammatory response and oxidative stress, that contributes to tissue damage and to neurodegenerative processes, typical of secondary injury, after TBI. Given the complex series of events that are involved after TBI injury, a multitarget pharmacological approach is needed. Artesunate is a more stable derivative of its precursor artemisin, a sesquiterpene lactone obtained from a Chinese plant Artemisia annua, a plant used for centuries in traditional Chinese medicine. artesunate has been shown to be a pluripotent agent with different pharmacological actions. therefore, in this experimental model of TBI we evaluated whether the treatment with artesunate at the dose of 30 mg\Kg, had an efficacy in reducing the neuroinflammatory process after TBI injury, and in inhibiting the NLRP3 inflammasome pathway, which plays a key role in the inflammatory process. We also assessed whether treatment with artesunate was able to exert a neuroprotective action by modulating the release of neurotrophic factors. our results show that artesunate was able to reduce the TBI-induced lesion, it also showed an anti-inflammatory action through the inhibition of Nf-kb, release of proinflammatory cytokines IL-1β and TNF-α and through the inhibition NLRP3 inflammasome complex, furthermore was able to reduce the activation of astrocytes and microglia (GFAP, Iba-1). Finally, our results show that the protective effects of artesunate also occur through the modulation of neurotrophic factors (BDNF, GDNF, NT-3) that play a key role in neuronal survival

protective effect of a new hyaluronic acid carnosine conjugate on the modulation of the inflammatory response in mice subjected to collagen induced arthritis

Abstract Several studies demonstrated the pharmacological actions of carnosine as well as hyaluronic acid (HA) during joint inflammation. In that regard, the aim of this study was to investigate the protective effect of a new HA -Carnosine conjugate (FidHycarn) on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). CIA was induced by two intradermal injections of 100 μl of an emulsion of collagen (CII) and complete Freund's adjuvant (CFA) at the base of the tail on day 0 and 21. At 35 day post CIA induction, the animals were sacrificed. CII injection caused erythema and edema in the hind paws, histological alterations with erosion of the joint cartilage as well as behavioral changes. Oral treatment with FidHycarn starting at the onset of arthritis (day 25) ameliorated the clinical signs, improved behavioral deficits as well as decreased histological and radiographic alterations. The degree of oxidative damage evaluated by inducible nitric oxide synthase (iNOS), nitrotyrosine, poly-ADP-ribose (PAR) expressions and malondialdehyde (MDA) levels, was also significantly reduced in Carnosine+HA association and FidHycarn treated mice. Moreover, the levels of proinflammatory cytokines and chemokines and cyclo-oxygenase COX-2 enzyme were also more significantly reduced by Carnosine+HA and FidHycarn compared to carnosine alone. However, interestingly, in some cases, the effects of FidHycarn were more important than Carnosine+HA association and not statistically different to methotrexate (MTX) used as positive control. Thus, the conjugation of Carnosine with HA (FidHycarn) could represent an interesting therapeutic strategy to combat arthritis disorders

Atrazine Inhalation Worsen Pulmonary Fibrosis Regulating the Nuclear Factor-Erythroid 2-Related Factor (Nrf2) Pathways Inducing Brain Comorbidities.

BACKGROUND/AIMS: Pulmonary fibrosis can be caused by genetic abnormalities, autoimmune disorders or exposure to environmental pollutants. All these causes have in common the excessive production of oxidative stress species that initiate a cascade of molecular mechanism underlying fibrosis in a variety of organs, including lungs. The chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Additionally, Bleomycin is a chemotherapeutic agent often used for different lymphoma with a seriously pulmonary complication. The most accredited hypothesis that may explain the mechanism of toxicity induced by ATR or bleomycin is exactly the production of reactive oxygen species (ROS) that leads to an unbalance in the physiological anti-oxidant system. However, until today, nobody has investigated the effect of ATR exposure during pulmonary fibrosis. METHODS: Mice were subject to ATR exposure, to bleomycin injection or to both. At the end of experiment, the lungs and blood were collected. Additionally, we analyzed by different test such as open field, pole and rotarod test or other we investigated the effects of ATR or bleomycin exposure on behavior. RESULTS: Following ATR or bleomycin induction, we found a significant increase in lung damage, fibrosis, and oxidative stress. This condition was significantly worsened when the animals injected with bleomycin were also exposed to ATR. Additionally, we observed significant motor and non-motor impairment in animals exposed to ATR. CONCLUSION: Our study demonstrates that ATR exposure, decrease nuclear factor-erythroid 2-related factor (Nrf2) pathways in both lung and brain

Physiological and Biochemical Changes in NRF2 Pathway in Aged Animals Subjected to Brain Injury.

Background/Aims: Oxidative stress plays a key role in aging, which in turn represents a substantial risk factor for brain injuries. The aim of the present study was to investigate the differences in physiological and biochemical changes in the brain during injury-related inflammation and oxidative stress, comparing young and old mice. Methods: Young and old mice were subjected to focal cerebral ischemia induced by transient middle cerebral artery occlusion or to traumatic brain injury performed by a controlled cortical impactor. At the end of both experiments, mice were sacrificed 24h after injuries and brains were collected to perform biochemical analysis. Results: In both ischemic stroke and traumatic brain injury, aging has not only led to damage-induced worsening of motor function and behavioural changes but also increased of infarct area compared to young animals. Moreover, aged mice show increased evidence of oxidative stress and reduced antioxidant capacity when compared to younger animals, as demonstrated by Nrf2-Keap1 signalling pathway and lower expression of antioxidant enzymes, such as HO-1, SOD-1 and GSH-Px. Additionally, brain tissues collected from elderly mice showed an increased IκB-α degradation into the cytoplasm and consequently NF-κB translocation into the nucleus, compared to young mice subjected to same injuries. The elderly mice showed significantly higher levels of iNOS and CoX-2 expression than the young mice, as well as higher levels of inflammatory cytokines such as TNFα, IL-1β, and IL-6 after MCAO and TBI. Conclusion: Preserving and keeping the NRF-2 pathway active counteracts the onset of oxidative stress and consequent inflammation after ischemic and traumatic brain insult, particularly in the elderly. Not only that, NRF-2 pathway could represent a possible therapeutic target in the management of brain injuries