Importance Of Oxidative Stress Research Articles

P0917N-ACETYL CYSTEINE FAILS TO IMPACT ON PLASMA ANTIOXIDANT CAPACITY IN BOTH A PLACEBO CONTROLLED CROSSOVER STUDY AND A PARALLEL GROUP TRIAL OF PATIENTS WITH CKD STAGE III: IMPLICATIONS FOR ITS USE AS A PROPHYLACTIC FOR CONTRAST INDUCED NEPHROPATHY

Abstract This project has been funded by the EU’s INTERREG VA programme, managed by the special EU Programmes Body (SEUPB) Background and Aims N-acetyl-L-cysteine (NAC) has been proposed as a prophylactic for the prevention of contrast induced nephropathy (CIN), a serious, adverse complication following administration of contrast media in patients with diabetes and chronic kidney disease (CKD). However, clinical trial results have failed to demonstrate consistently the beneficial qualities of NAC in this setting. The suggested mechanism by which NAC has been proposed to be effective is via antioxidant activity, but NAC itself appears not to be a powerful antioxidant; intracellular conversion of NAC to glutathione (GSH) is essential for antioxidant effects. We tested the hypothesis that oral or intravenous NAC fails to increase antioxidant activity in the plasma of healthy volunteers or CKD stage III patients undergoing elective coronary angiography. Method 16 healthy volunteers (8 receiving contrast media) and 8 patients with chronic renal failure were recruited to 3 separate groups as a part of a crossover design study. 66 patients with CKD stage III undergoing elective coronary angiography were recruited to a parallel group randomized controlled trial. Each volunteer or patient was randomised to receive NAC (i.v.; 50 mg/kg/hr infusion for 2 h, followed by 20 mg/kg/hr infusion for a further 5 h), or NAC (oral; 1200 mg twice daily, commencing the day before the study visit) or placebo. Participants attended the Clinical Research Facility on three occasions for the crossover groups, but only once in the parallel group trial. Patients were infused with para-aminohippurate (PAH) and inulin to enable measurement of renal function parameters. Plasma and paired buffy coat samples were collected at several time points for 2 hours before contrast infusion and for 6 hours after. Samples were used to measure various clinical parameters, along with intracellular and plasma thiol concentrations and the plasma antioxidant capacity (oxygen radical antioxidant capacity; ORAC). Results Plasma NAC concentrations peaked at 222 µM (healthy volunteers), 354 µM (CKD patients), 271 µM (healthy volunteers receiving contrast) and 348 µM (CKD patients undergoing elective coronary angiography) following infusion of NAC. The corresponding peak concentrations were ∼2 µM following oral NAC across all groups. No comparable increase in the plasma compartment ORAC antioxidant capacity was measured in any of the treatment groups. Equally, contrast infusion itself did not significantly reduce antioxidant capacity in plasma, even in the placebo group. Buffy coat measures showed that there was a significant increase of intracellular GSH in some patients. Also, no clear additional benefit was witnessed by increasing plasma NAC ∼100-fold through infusion of NAC over oral administration. Conclusion NAC fails to influence ORAC antioxidant capacity in the plasma compartment of CKD stage III patients receiving contrast media. Our results question the importance of oxidative stress in contrast-induced nephropathy. Furthermore, the findings fail to demonstrate a direct antioxidant impact of NAC in the plasma compartment and question the antioxidant hypothesis related to contrast-induced nephropathy and NAC.

NF-κB and Keap1 Interaction Represses Nrf2-Mediated Antioxidant Response in Rabbit Hemorrhagic Disease Virus Infection.

The rabbit hemorrhagic disease virus (RHDV), which belongs to the family Caliciviridae and the genus Lagovirus, causes lethal fulminant hepatitis in rabbits. RHDV decreases the activity of antioxidant enzymes regulated by Nrf2 in the liver. Antioxidants are important for the maintenance of cellular integrity and cytoprotection. However, the mechanism underlying the regulation of the Nrf2-antioxidant response element (ARE) signaling pathway by RHDV remains unclear. Using isobaric tags for relative and absolute quantification (iTRAQ) technology, the current study demonstrated that RHDV inhibits the induction of ARE-regulated genes and increases the expression of the p50 subunit of the NF-κB transcription factor. We showed that RHDV replication causes a remarkable increase in reactive oxygen species (ROS), which is simultaneously accompanied by a significant decrease in Nrf2. It was found that nuclear translocation of Keap1 plays a key role in the nuclear export of Nrf2, leading to the inhibition of Nrf2 transcriptional activity. The p50 protein partners with Keap1 to form the Keap1-p50/p65 complex, which is involved in the nuclear translocation of Keap1. Moreover, upregulation of Nrf2 protein levels in liver cell nuclei by tert-butylhydroquinone (tBHQ) delayed rabbit deaths due to RHDV infection. Considered together, our findings suggest that RHDV inhibits the Nrf2-dependent antioxidant response via nuclear translocation of Keap1-NF-κB complex and nuclear export of Nrf2 and provide new insight into the importance of oxidative stress during RHDV infection.IMPORTANCE Recent studies have reported that rabbit hemorrhagic disease virus (RHDV) infection reduced Nrf2-related antioxidant function. However, the regulatory mechanisms underlying this process remain unclear. The current study showed that the NF-κB p50 subunit partners with Keap1 to form the Keap1-NF-κB complex, which plays a key role in the inhibition of Nrf2 transcriptional activity. More importantly, upregulated Nrf2 activity delayed the death of RHDV-infected rabbits, strongly indicating the importance of oxidative damage during RHDV infection. These findings may provide novel insights into the pathogenesis of RHDV.

Plant Polyphenols as Neuroprotective Agents in Parkinson's Disease Targeting Oxidative Stress.

Parkinson's disease (PD) is the second most prevalent progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the human midbrain. Various ongoing research studies are competing to understand the pathology of PD and elucidate the mechanisms underlying neurodegeneration. Current pharmacological treatments primarily focused on improving dopamine metabolism in PD patients, despite the side effects of long-term usage. In recent years, it is recognized that oxidative stress-mediated pathways lead to neurodegeneration in the brain, which is associated with the pathophysiology of PD. The importance of oxidative stress is often less emphasized when developing potential therapeutic approaches. Natural plant antioxidants have been shown to mediate the oxidative stress-induced effects in PD, which has gained considerable attention in both in vitro and in vivo studies. Yet, clinical trials on natural polyphenol compounds are limited, restricting the potential use of these compounds as an alternative treatment for PD. Therefore, this review provides an understanding of the oxidative stress-induced effects in PD by elucidating the underlying events contributing to oxidative stress and explore the potential use of polyphenols in improving the oxidative status in PD. Preclinical findings have supported the potential of polyphenols in providing neuroprotection against oxidative stress-induced toxicity in PD. However, limiting factors, such as safety and bioavailability of polyphenols, warrant further investigations so as to make them the potential target for clinical applications in the treatment and management of PD.

Methyl parathion causes genetic damage in sperm and disrupts the permeability of the blood-testis barrier by an oxidant mechanism in mice

Methyl parathion (Me-Pa) is an extremely toxic organophosphorus pesticide still used in developing countries. It has been associated with decreased sperm function and fertility and with oxidative and DNA damage. The blood-testis barrier (BTB) is a structure formed by tight junction (TJ) proteins in Sertoli cells and has a critical role in spermatogenesis. We assessed the effect of repeated doses of Me-Pa (3−12 mg/kg/day for 5 days, i.p.) on sperm quality, lipid oxidation, DNA integrity, and BTB permeability in adult male mice and explored oxidation as a mechanism of toxicity. Me-Pa caused dose-dependent effects on sperm quality, lipoperoxidation, and DNA integrity. Testis histology results showed the disruption of spermatogenesis progression and atrophy of seminiferous tubules. The pesticide opened the BTB, as evidenced by the presence of a biotin tracer in the adluminal compartment of the seminiferous tubules. This effect was not observed after 45 days of exposure when a spermatogenic cycle had completed. The coadministration of the antioxidant α-tocopherol (50 mg/kg/day for 5 days, oral) prevented the effects of Me-Pa on sperm quality, DNA and the BTB, indicating the importance of oxidative stress in the damage generated by Me-Pa. As evidenced by immunochemistry, no changes were found in the localization of the TJ proteins of the BTB, although oxidation (carbonylation) of total proteins in testis homogenates was detected. Our results show that Me-Pa disturbs the BTB and that oxidation is involved in the observed toxic effects on sperm cells.

Adjuvant Therapies in Diabetic Retinopathy as an Early Approach to Delay Its Progression: The Importance of Oxidative Stress and Inflammation.

Diabetes mellitus (DM) is a progressive disease induced by a sustained state of chronic hyperglycemia that can lead to several complications targeting highly metabolic cells. Diabetic retinopathy (DR) is a multifactorial microvascular complication of DM, with high prevalence, which can ultimately lead to visual impairment. The genesis of DR involves a complex variety of pathways such as oxidative stress, inflammation, apoptosis, neurodegeneration, angiogenesis, lipid peroxidation, and endoplasmic reticulum (ER) stress, each possessing potential therapeutic biomarkers. A specific treatment has yet to be developed for early stages of DR since no management is given other than glycemic control until the proliferative stage develops, offering a poor visual prognosis to the patient. In this narrative review article, we evaluate different dietary regimens, such as the Mediterranean diet, Dietary Pattern to Stop Hypertension (DASH) and their functional foods, and low-calorie diets (LCDs). Nutraceuticals have also been assessed in DR on account of their antioxidant, anti-inflammatory, and antiangiogenic properties, which may have an important impact on the physiopathology of DR. These nutraceuticals have shown to lower reactive oxygen species (ROS), important inflammatory factors, cytokines, and endothelial damage biomarkers either as monotherapies or combined therapies or concomitantly with established diabetes management or nonconventional adjuvant drugs like topical nonsteroidal anti-inflammatory drugs (NSAIDs).

The effect of coenzyme Q10 supplementation on oxidative stress status and insulin resistance in diabetic rats

Background and Aim: Coenzyme Q10 is an antioxidant it is now used in diseases associated with oxidative stress. Given the importance of oxidative stress in the complications of diabetes, this study aimed to investigate the effect of CoQ10 supplementation on the status of oxidative stress and insulin resistance was performed in diabetic rats. Materials and Methods: 18 Sprague-Dawley male rats were randomly divided into 3 groups (n=6). The control group received the physiological serum, the diabetic group (STZ: 55 mg/kg) received sesame oil, and the supplement group, which was diabetic, received Q10 intraperitoneal (i.p) at a dose of 2 mg/kg per day for 10 days. At the end of the tenth day, a venous blood sample was collected. Plasma levels of glucose, insulin, vitamin D, total antioxidant capacity, malondialdehyde (MDA), and protein thiol groups were measured using the corresponding colorimetric methods. Results: The results showed that treatment of diabetic rats with CoQ10 supplementation significantly reduced fasting blood sugar (FBS) and MDA levels and significantly increased serum insulin and vitamin D levels compared to diabetic rats (P<0.05).The average weight, thiol groups, insulin resistance, and total antioxidant capacity in the treated diabetic rats with CoQ10 supplementation varied compared with the diabetic control group but were not significant (p>0.05). Conclusion: Consumption of CoQ10 supplementation can reduce the oxidative stress caused by diabetes through its antioxidant effects. Key Words: Antioxidant; Coenzyme Q10; Diabetes Mellitus; Vitamin D

The Importance of Oxidative Stress in Determining the Functionality of Mammalian Spermatozoa: A Two-Edged Sword.

This article addresses the importance of oxidative processes in both the generation of functional gametes and the aetiology of defective sperm function. Functionally, sperm capacitation is recognized as a redox-regulated process, wherein a low level of reactive oxygen species (ROS) generation is intimately involved in driving such events as the stimulation of tyrosine phosphorylation, the facilitation of cholesterol efflux and the promotion of cAMP generation. However, the continuous generation of ROS ultimately creates problems for spermatozoa because their unique physical architecture and unusual biochemical composition means that they are vulnerable to oxidative stress. As a consequence, they are heavily dependent on the antioxidant protection afforded by the fluids in the male and female reproductive tracts and, during the precarious process of insemination, seminal plasma. If this antioxidant protection should be compromised for any reason, then the spermatozoa experience pathological oxidative damage. In addition, situations may prevail that cause the spermatozoa to become exposed to high levels of ROS emanating either from other cells in the immediate vicinity (particularly neutrophils) or from the spermatozoa themselves. The environmental and lifestyle factors that promote ROS generation by the spermatozoa are reviewed in this article, as are the techniques that might be used in a diagnostic context to identify patients whose reproductive capacity is under oxidative threat. Understanding the strengths and weaknesses of ROS-monitoring methodologies is critical if we are to effectively identify those patients for whom treatment with antioxidants might be considered a rational management strategy.

Reperfusion syndrome: state of the art

Reperfusion syndrome is a complex series of clinical manifestations resulting from restoration of blood flow to previously ischaemic tissues. It is accompanied by damage to cells, tissues and organs at various levels, followed by the development of multiple organ failure. This review deals with the main pathophysiological mechanisms of the development of reperfusion syndrome in lesions of cardiac, cerebral and lower-limb vessels. Oxidative stress is considered to be the most important marker of ischaemia-reperfusion injury irrespective of the type of tissues affected. Presented herein are the data on contemporary possibilities of influencing various stages and components of the development of reperfusion injury by means of drug therapy, demonstrating that due to the importance of oxidative stress as a key link of reperfusion injury, antioxidant therapy should be the main component of prevention and treatment of reperfusion injury.

The SOD Mimic MnTnHex-2-PyP5+ Reduces the Viability and Migration of 786-O Human Renal Cancer Cells.

Clear-cell renal carcinoma (ccRCC) is the most common type of renal cancer. The importance of oxidative stress in the context of this disease has been described, although there is only little information concerning the role of superoxide dismutase (SOD) enzymes. The importance of SOD in different pathological conditions promoted the development of SOD mimics (SODm). As such, manganese(III) porphyrins can mimic the natural SOD enzymes and scavenge different reactive oxygen species (ROS), thus modulating the cellular redox status. In this study, the exposure of 786-O human renal cancer cells to MnTnHex-2-PyP5+ (MnP), a very promising SODm, led to a concentration and time-dependent decrease in cell viability and in the cell proliferation indices, as well as to an increase in apoptosis. No relevant effects in terms of micronuclei formation were observed. Moreover, the exposure to MnP resulted in a concentration-dependent increase in intracellular ROS, presumably due to the generation of H2O2 by the inherent redox mechanisms of MnP, along with the limited ability of cancer cells to detoxify this species. Although the MnP treatment did not result in a reduction in the collective cell migration, a significant decrease in chemotactic migration was observed. Overall, these results suggest that MnP has a beneficial impact on reducing renal cancer cell viability and migration and warrant further studies regarding SODm-based therapeutic strategies against human renal cancer.

Hyperviscous Semen Causes Poor Sperm Quality and Male Infertility through Induction of Oxidative Stress

Background/Aims: Semen hyperviscosity (SHV) is one of the significant factors involved in poor semen quality and male infertility. It also leads major problems during assisted reproduction techniques and in vitro fertilization process. Although influence of SHV on sperm quality, fertilization rate and male infertility have been widely considered, molecular and cellular mechanisms for these abnormalities are not well understood. In this review, we aimed to discuss the proposed cellular and molecular mechanisms of SHV on male reproductive system, the importance of oxidative stress (OS) and the mechanisms by which SHV induces OS and impairment of other antioxidants. Methods: A PubMed/Medline and EM-BASE search was performed using keywords: “hyperviscosity semen”, “oxidative stress”, and “male infertility”. Conclusion: OS induced by reactive oxygen species can be considered as a major mechanism in patients with hyperviscosity semen that is associated with DNA fragmentation, lipid peroxida-tion and sperm membrane disintegrity, apoptosis, depletion of antioxidants, and subsequently poor sperm quality and male infertility. Therefore, antioxidant therapy may improve main pathological effects of hyperviscosity semen, especially oxidative damages and inflammation, on sperm quality and function. Further, randomized controlled studies are necessary to confirm these results and make a comparison between effects of various antioxidants such as N-acethyl-cysteine and Curcumin on fertility problem in patients with hyperviscous semen.

Evaluation of thiol/disulfide homeostasis in patients with pityriasis rosea

Purpose: Pityriasis rosea (PR) is a common, self-limiting, inflammatory skin disease with an acute onset. The etiology of PR is not yet clearly known but the defect in the oxidation system involved in many papulosquamous skin diseases may play a role. Thiol/disulfide homeostasis is a new marker of oxidative stress and has been studied in many diseases in recent years. The aim of this study to investigate thiol/disulfide homeostasis in PR patients.Material and methods: Thirty-four patients (18 females, 16 males; median age 26 years) that presented to the Dermatology Clinic of Istanbul Medipol Mega University Hospital between November 2017 and December 2018 and were clinically and/or histopathologically diagnosed with PR, and 30 healthy individuals (16 females, 14 males; median age 27 years) were included in the study. The serum native thiol and total thiol were measured by a novel colorimetric, automated method. The disulfide levels and disulfide/native thiol ratios were also calculated from these measured parameters.Results: There was no statistically significant difference in the serum native thiol and total thiol concentration between the PR and control groups (p = 0.711 and 0.788, respectively). Disulfide, disulfide/native thiol, and disulfide/total thiol levels were significantly higher in patients with PR (p = 0.002, 0.006 and 0.006, respectively).Conclusions: The thiol-disulfide balance shifted toward disulfide in patients with PR. This demonstrates the importance of oxidative stress in the etiopathogenesis of PR using a new marker.

Oxidative stress and deregulations in base excision repair pathway as contributors to gallbladder anomalies and carcinoma – a study involving North-East Indian population

Gallbladder cancer (GBC) is a fatal condition with dismal prognosis and aggressive local invasiveness; and with uncharacterised molecular pathology relating to non-specific therapeutic modalities. Given the importance of oxidative stress in chronic diseases and carcinogenesis, and the lacunae in literature regarding its role in gallbladder diseases, this study aimed to study the involvement of oxidative stress and deregulation in the base excision repair (BER) pathway in the pathogenesis of gallbladder diseases including GBC. This study involved patients from the North-East Indian population, where the numbers of reported cases are increasing rapidly and alarmingly. Oxidative stress, based on 8-OH-dG levels, was found to be significantly higher in gallbladder anomalies (cholelithiasis [CL] and cholecystitis [CS]) and GBC at the plasma and DNA level, and was associated with GBC severity. The expressions of key BER pathway genes were downregulated in gallbladder anomalies and GBC compared to controls, and in GBC compared to both non-neoplastic controls and gallbladder anomalies. Expression of XRCC1 and hOGG1 was significantly associated with both susceptibility and severity of GBC. The XRCC1 codon280 polymorphism was associated with disease susceptibility; and significantly higher oxidative stress was observed in hOGG1 genotypic variants. The genomes of GBC patients were found to be more hypermethylated compared to controls, with the promoters of XRCC1 and hOGG1 being hypermethylated and, therefore, being silenced. This study underlined the prognostic significance of the oxidative stress marker 8-OH-dG and BER pathway genes, especially hOGG1 and XRCC1, in gallbladder anomalies and GBC, as well as stated their potential for therapeutic targeting.

SERUM STATUS OF ENDOGENOUS ANTIOXIDANT M ARKERS: BILIRUBIN, ALBUMINS, TOTAL PROTEINS AND CREATININE IN MYASTHENIA GRAVIS PATIENTS

There is a lot of evidence pertaining to the ethiopathogenetic importance of oxidative stress in a number of autoimmune diseases, including some immune-mediated neurological diseases such as multiple sclerosis. However, the role of oxidative stress and oxidative status in patients with myasthenia gravis is still an under-researched area. The aim of our research was to compare serum total and direct bilirubin, albumin, total proteins and creatinine levels in myasthenia gravis (MG) patients with healthy controls, and patients with multiple sclerosis (MS). The subjects were divided into three groups (92 MG patients, 68 healthy controls and 74 MS patients). All MG patients were newly diagnosed, classified with MGFA Clinical Classification, and divided into two groups regarding onset age (early < 50 years, late ≥50 years), sex (male, female), thymus pathology (present, absent). Serum antioxidant status was significantly lower in MG and MS group compared to the healthy controls (p < 0.05). There was no significant difference in serum antioxidant status between patients with MG and those with MS. Regarding MGFA Classification we have not found any correlation with serum levels of measured parameters. Our findings suggested that there was a potential role of oxidative process in MG pathology. Among the analyzed parameters, direct bilirubin showed significantly lower value in women, the elderly and in the group of MG patients with pathologically altered thymus gland.

Does curcumin or metformin attenuate oxidative stress and diabetic nephropathy in rats?

Background: Since the importance of oxidative stress in the development of diabetic nephropathy (DN) has previously been established, the therapeutic effects of various natural antioxidant agents or synthetic drugs have so far been investigated. Objectives: The aim of this study was to investigate the beneficial effects of curcumin (a natural polyphenol) and metformin (a common therapeutic medicine for type 2 diabetes) on oxidative status in kidney of type 1 diabetic rats. Materials and Methods: In this experimental study 60 male Wistar rats were divided into 10 groups. Type 1 diabetes was induced by streptozotocin. Rats received chow diet and treated with either normal saline in control (N) and diabetic control (D) groups or different doses of metformin (Met) (300 or 500 mg/kg body weight) or curcumin (Cur) (50 or 150 mg/kg body weight) in N+Met300, N+Met500, N+Cur50, N+Cur150, D+Met300, D+Met500, D+Cur50, and D+Cur150 groups. Urinary creatinine, urea, and protein were measured. Total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), and the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase were assessed in kidney tissues. Results: Both metformin and curcumin showed significant effects on urinary creatinine, urea, and protein levels (P value for all was &lt;0.001). Unlike metformin, curcumin completely restored TAC and TOS (P&lt;0.001), and MDA (P=0.012) in kidney tissues and significantly recovered the activities of SOD (P= 0.003), GPx (P&lt; 0.001), and catalase (P=0.011). Conclusions: Curcumin was found more effective than metformin in attenuating oxidative status in DN.

Sialic Acid-Functionalized PEG-PLGA Microspheres Loading Mitochondrial-Targeting-Modified Curcumin for Acute Lung Injury Therapy.

Acute lung injury (ALI) is a serious illness without resultful therapeutic methods commonly. Recent studies indicate the importance of oxidative stress in the occurrence and development of ALI, and mitochondria targeted antioxidant has become a difficult and hot topic in the research of ALI. Therefore, a sialic acid (SA)-modified lung-targeted microsphere (MS) for ALI therapy are developed, with triphenylphosphonium cation (TPP)-modified curcumin (Cur-TPP) loaded, which could specifically target the mitochondria, increasing the effect of antioxidant. The results manifest that with the increase of microsphere, lung distribution of microsphere is also increased in murine mice, and after SA modification, the microsphere exhibits the ideal lung-targeted characteristic in ALI model mice, due to SA efficiently targeting to E-selectin expressed on inflammatory tissues. Further investigations indicate that SA/Cur-TPP/MS has better antioxidative capacity, decreases intracellular ROS generation, and increases mitochondrial membrane potential, contributing to a lower apoptosis rate in human umbilical vein endothelial cells (HUVECs) compared to H2O2 group. In vivo efficacy of SA/Cur-TPP/MS demonstrates that the inflammation has been alleviated markedly and the oxidative stress is ameliorated efficiently. Significant histological improvements by SA/Cur-TPP/MS are further proved via HE stains. In conclusion, SA/Cur-TPP/MS might act as a promising drug formulation for ALI therapy.

Determination of Parameters of Oxidative Stress in vitro Models of Neurodegenerative Diseases-A Review.

Oxidative stress is a major mechanism underlying the development of various neurodegenerative diseases (Alzheimer, Parkinson, Huntington and amyotrophic lateral sclerosis). Excessive formation of reactive oxygen species (ROS) and nitrogen (RNSs) can overburden the ability of the enzymatic antioxidant defense mechanisms (superoxide dismutase, catalase and glutathione reductase) and non-enzymatic (uric acid, ascorbic acid, α-tocopherol and reduced glutathione), causing the development of oxidative stress, and consequently, impairing the neuronal system cells by means of oxidative damage to a variety of important biological molecules such as lipids, DNA and proteins. Considering the importance of oxidative stress in neurodegenerative diseases, the present review aims to address the main parameters evaluated in in vitro studies on oxidative stress in different models of neurodegenerative diseases.The literary review was conducted through Pubmed, Science Direct, LILACS, Scielo and Google using following keywords: oxidative stress, neurodegenerative diseases and parameters of oxidative stress. We selected articles published between 2002 and 2017.The in vitro evaluation of the oxidative stress related parameters has provided a preliminary view about the pathogenesis of many neurodegenerative diseases (Alzheimer's, Parkinson's, Huntington's and Amyotrophic lateral sclerosis). In this way, it has demonstrated the mechanism of action of ROS/RNSs in these diseases by direct or indirect detection through several experimental procedures in vitro.

Toward understanding genomic instability, mitochondrial dysfunction and aging.

The biology of aging is an area of intense research, and many questions remain about how and why cell and organismal functions decline over time. In mammalian cells, genomic instability and mitochondrial dysfunction are thought to be among the primary drivers of cellular aging. This review focuses on the interrelationship between genomic instability and mitochondrial dysfunction in mammalian cells and its relevance to age-related functional decline at the molecular and cellular level. The importance of oxidative stress and key DNA damage response pathways in cellular aging is discussed, with a special focus on poly (ADP-ribose) polymerase 1, whose persistent activation depletes cellular energy reserves, leading to mitochondrial dysfunction, loss of energy homeostasis, and altered cellular metabolism. Elucidation of the relationship between genomic instability, mitochondrial dysfunction, and the signaling pathways that connect these pathways/processes are keys to the future of research on human aging. An important component of mitochondrial health preservation is mitophagy, and this and other areas that are particularly ripe for future investigation will be discussed.

Mechanisms of diazinon effects on impaired spermatogenesis and male infertility.

Diazinon (DZN) is an organophosphate insecticide that has cytotoxic and pathological effects on the reproductive system. It causes a wide variety of pathological effects on the reproductive system such as testicular atrophy, disturbance in sex hormones, impaired spermatogenesis, low quality of sperm, and fertility problems. However, molecular and cellular mechanisms of its adverse effects are not well understood. General events such as testicular damage, inflammation, mitochondrial deficiency, DNA fragmentation, disintegration of sperm plasma membrane, apoptosis, and cell death are observed in DZN-exposed animals. Oxidative stress (OS) induced by reactive oxygen species may be a main mechanism, which can be associated with sperm DNA fragmentation, reduced integrity of sperm cell membrane, apoptosis, depletion of antioxidants, and subsequently poor sperm quality and male infertility. Therefore, identification of these pathways may provide valuable information regarding the mechanisms of DZN action on the male reproductive system. In this review, we aim to discuss the proposed cellular and molecular mechanisms of DZN action on male reproductive system, the importance of OS and mechanisms by which DZN induces OS and depletion of other antioxidants.

Laser-based spectrometer for optical trace gas detection in young adults with autism

Autism is known as a complex neurodevelopmental disability that involve a combination of impairments in communication, reciprocal social interaction, and stereotypic behaviors. Many studies linked oxidative stress (OS) with the etiopathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. The aim of our study was to evaluate ethylene as a by-products of OS in human body, in people with autism. We used a laser-based spectrometer for optical trace ethylene detection. The results indicated that OS was not significantly increased in this disorder. As a by-product of OS exhaled ethylene from adults with autism presented very small concentration differences compared to healthy controls. The possible responsible factor for the normality between the concentrations of breath ethylene at young adults with autism and control adults could be explained by the antioxidants intake together with the lifestyle and dietary patterns. Additional studies are needed to determine carefully which antioxidant will have the greatest therapeutic benefit considering the importance of oxidative stress in many biological reactions.

Abstract P307: pNaKtide Attenuates Dyslipidemia and Atherosclerosis by Blocking Na/K- ATPase/Reactive Oxygen Species Amplification in ApoE -/- Mice

Background: We have previously reported that the α1 subunit of the sodium potassium adenosine triphosphatase (Na/K-ATPase) acts as an amplifier for reactive oxygen species (ROS) in addition to its ion pumping function. We have also shown that blockade of this amplification with a novel peptide, pNaKtide, ameliorates oxidative stress and obesity in mice subjected to a high-fat diet. Hypothesis: Given the importance of oxidative stress in the pathophysiology of atherosclerosis, we chose to examine whether pNaKtide might be effective in ameliorating dyslipidemia and atherosclerosis in ApoE -/- mice. Methods: pNaKtide was administered in ApoE -/- mouse fed western diet. 25 mg/Kg pNaKtide was administered intraperitoneally once every 7 days. Lipid profile, glucose insulin levels, and ROS levels were measured. Aortas were dissected and quantification of aortic lesions was done. Results: Our results show that pNaKtide improved glucose tolerance and HOMA-IR scores in ApoE-/- mice fed a western diet (p&lt;0.05). Also, pNaKtide administered to these mice significantly decreased plasma ALT, triglycerides, FFA, and LDL levels. Further, our results show that ApoE -/- mice fed a western diet had decreased plasma HDL levels and this decrease was reversed by pNaKtide. Plasma ROS levels were significantly attenuated by pNaKtide treatment. Mice fed a western diet had increased plaque size. Plaque size was significantly decreased by pNaKtide treatment. Conclusion: This study suggests that the Na/K-ATPase/ROS signaling cascade is a possible mechanism for the development of dyslipidemia and atherosclerosis associated with the metabolic syndrome phenotype and pNaKtide presents a potential novel treatment for these pathologies.