Excess Amounts Of Free Radicals Research Articles

Marked Reduction of Oxidant Species after Sulfureous Crenotherapy in Females with Joint Diseases and Psoriasis: A Retrospective Real-Life Study.

Oxidative stress, a condition induced by an excessive amount of free radicals, such as reactive oxygen species (ROS), shows several gender-related differences in basal cellular redox state and antioxidant responses. Crenotherapy with sulfureous mineral water can improve the cellular redox state. In this retrospective observational study, gender-related differences in the efficacy of sulfureous crenotherapy in decreasing oxidant species were investigated. Seventy-eight patients, stratified by sex, with osteoarthritis or degenerative joint disease and Vulgar psoriasis who have received a cycle of sulfureous mud-bath therapy + sulfureous hydropinotherapy were enrolled. Plasma concentration of oxidant species and clinical outcomes were measured at baseline and at the end of treatment. After 2 weeks of sulfureous crenotherapy, a significant amelioration of clinical outcomes and a significant reduction of oxidant species were observed in both sexes, more marked in females than in males (p = 0.0001 and p = 0.04, respectively). For patients with high oxidant species at baseline, females showed a greater reduction in itching compared to males (-95% vs. -50%), while men had a higher amelioration in pain and morning stiffness (-45% vs. -32%, and -50% vs. -37%, respectively). In conclusion, sulfureous crenotherapy can be a valuable strategy to improve cellular redox state in both sexes.

Free Radical and Viral Infection: A Review from the Perspective of Ferroptosis.

Free radicals, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), play critical roles in various physiological activities such as cell differentiation, apoptosis, and vascular tension when existing in cells at low levels. However, excessive amounts of free radicals are harmful, causing DNA damage, lipid peroxidation, protein degeneration, and abnormal cell death. Certain viral infections induce cells to produce excessive free radicals, which in multiple ways help the virus to replicate, mature, and exit. Iron is a necessary element for many intracellular enzymes, involved in both cellular activities and viral replication. Ferroptosis, a programmed cell death mode distinct from apoptosis, necrosis, and pyroptosis, is characterized by lipid peroxide accumulation and damage to the antioxidant system, affecting many cellular processes. Viral infection commonly manifests as decreased glutathione (GSH) content and down-regulated glutathione peroxidase 4 (GPX4) activity, similar to ferroptosis. Recent studies have suggested a possible relationship among free radicals, viral infections and ferroptosis. This review aims to elucidate the molecular mechanism linking free radicals and ferroptosis during viral infections and provide a new theoretical basis for studying viral pathogenesis and control.

Phytochemical Analysis, Antioxidant and Anticancer Effects of Clitoria ternatae Extract on Breast T47D Cancer Cells

Background: Breast cancer is one of the most common and deadly forms of cancer in the world. Cancer is a multi-factorial disease. Genetic factors, environment and lifestyle have a role in the development of cancer. One of the mechanisms of cancer development is when an imbalance between free radicals and antioxidants in the human body occurs. Uncontrolled and excessive amount of free radicals and cause cell damage and uncontrolled cell growth. Clitoria ternate is a plant that is often found in Asia and many of the benefits of this flower have been studied. This study aims to determine the phytochemical constituents, antioxidant activity, and cytotoxic activity of Clitoria ternatea against T47D breast cancer cells. Method: Clitoria ternatea in the form of dry powder is macerated in a multi-level manner with n-hexane, ethyl acetate, and ethanol as solvents, producing a Clitoria ternatea extract of the respective solvents. Each extract is then evaluated for its phytochemical constituents, antioxidant activity, and cytotoxic activity using phytochemical test, thin layer chromatography (TLC), DPPH assay, and MTT assay respectively. Results: Phytochemical analysis of Clitoria ternatea shows the presence of glycosides, flavonoids, tannins and triterpenoids with TLC revealing the presence of ten phytochemical constituents. DPPH assay reveals that Clitoria ternatea exhibits a very active antioxidant activity. MTT assay revels Clitoria ternatea has a high cytotoxic activity towards T47D breast cancer cell line with IC50 value ranging from 1.27 μg/mL to 32.38 μg/mL. Conclusion: Chemical constituents of Clitoria ternatea is responsible for the antioxidant and cytotoxic activity towards T47D breast cancer cell line.

New Entity-Thalassemic Endocrine Disease: Major Beta-Thalassemia and Endocrine Involvement.

New Entity-Thalassemic Endocrine Disease: Major Beta-Thalassemia and Endocrine Involvement.

Formulation and Evaluation of instant granules from Ketapang Badak fruit (Ficus lyrata Warb) using wet granulation method as an antioxidant supplement

Free radicals are naturally produced from the body's metabolic processes, but the excessive amount of free radicals can interfere with human health because they cause oxidative stress. Therefore we need antioxidants that can protect against free radicals. Ficus lyrata W. is one of the antioxidant sources. This study aims to formulate instant granules from the Ethanol extract of Ficus lyrata W. using the wet granulation method. The formula is optimized using the Design Expert with the two-level factorial method. The optimized factors are xanthan gum 0,8-1,5% and PVP 0,5-5%. Granules are evaluated and analyzed using a Design Expert. The results obtained showed that Formula 4 with a combination of xanthan gum 0,8% and PVP 5% is the best formula, which the evaluation result is Loss On Drying (LOD) 3,28%, Flowability 16.043 ± 0.221 (g/s), Angle of Rest 21.77 ± 0.862, no precipitate for15 minutes, pH = 4.7, dispersed in 31 seconds and sedimentation time is 52.213 ± 1.7878 (minutes), the results of the antioxidant activity test of the ethanol extract of Ficus lyrata is 38,27 µg/ml, and instant granules is 145,02 µg/ml.Keywords: Antioxidant, Ficus lyrata W., Instant granules, Design expert

Oxidative stress indices in ASD children in Sub-Sahara Africa

BackgroundThe pathogenesis of autism spectrum disorder (ASD) remains a medical challenge even in the developed world. Although genetics and epigenetic factors have been variously indicted as major causes of the disorder, development of oxidative stress especially in the formative years of children has equally gained prominence as an etiological basis of the disorder. Oxidative stress is characterized by the production of excessive amounts of free radicals, decreased levels of antioxidants with the attendant imbalance in oxidant/antioxidant ratio. This study was designed to determine the levels of essential metals [magnesium (Mg), zinc (Zn), and copper (Cu)] and toxic metal, lead (Pb), and generation of oxidative stress by their abnormal interaction.MethodTwenty-five children clinically diagnosed for ASD according to DSM-IV-TR and 25 neuro-typical (NT) children (controls), (aged 5.96 ± 1.40 years and 6.18 ± 2.59 years respectively) were recruited for this study. Essential and toxic metals were analyzed using induction-coupled plasma-mass spectrometry (ICP-MS); oxidative stress markers [malondialdehyde (MDA), total plasma peroxidase (TPP), and total antioxidant capacity (TAC)] were determined using appropriate biochemical methods. Oxidative stress index (OSI) was calculated.ResultsThe levels of TPP and TAC were significantly reduced while MDA was higher in ASD compared to NT. Although OSI was higher in ASD, the difference was not significant. Pb (lead) concentration was significantly increased while Mg, Zn, and Cu levels were reduced significantly in ASD compared to NT. A significant negative correlation between Mg and OSI (r = − 0.438; p = 0.029) was observed in NT.ConclusionReduction in Zn and Mg levels with a concurrent increase in Pb in children with ASD in this study may be the basis of inadequate TAC manifesting as increased MDA and reduced TPP levels. The attendant imbalance in oxidant/antioxidant ratio may result in abnormality in neuronal transduction leading to the abnormal cognitive and speech functions characteristic of ASD.

Effect of glutathione administration as adjuvant therapy to NO and MDA level in Wistar rat peritonitis model

Background: Excessive amounts of free radicals beyond the antioxidant levels in the body will cause a condition called oxidative stress. Nitric oxide (NO) and malondialdehyde (MDA) are produced under conditions of oxidative stress. Glutathione (GSH) is the most endogenous antioxidant synthesized in humans. Therefore this study aims to prove whether the administration of glutathione as an adjuvant therapy can reduce levels of NO and MDA in peritonitis.Methods: This is an experimental study with a post-test-only control group design. Twenty-four Wistar rats were randomly divided into four groups (6 rats/group). The first group (C) was a control group. The second group (P) was induced by peritonitis. The third group (P+Cef) was peritonitis-induced groups with given Ceftriaxone injection as therapy. The fourth group (P+Cef+Glu) was peritonitis-induced groups with given Ceftriaxone injection and glutathione as adjuvant therapy. After 24 hours, blood samples were taken for examination of NO and MDA levels. Data is considered significant if the p-value <0.05.Results: There was a significant increase in NO level from Group 2 to Group 4 (P<0,05). There were no significant differences between MDA levels groups (P>0,05).Conclusion: Glutathione as adjuvant therapy is not adequate to reduce NO and MDA levels in peritonitis.

Putative abrogation impacts of Ajwa seeds on oxidative damage, liver dysfunction and associated complications in rats exposed to carbon tetrachloride.

Industrial toxicants such as Carbon tetrachloride (CCl4) are known to disrupt the oxidative-antioxidative balance, which generates excessive amounts of free radicals leading to chronic or acute liver damage. Natural antioxidants, including Ajwa, play an important role in protecting against hepatotoxicity. This study investigated the prophylactic impacts of ajwa seeds aqueous extract (ASE) against hepatic oxidative injury in rats induced by CCl4. Eighty male Wistar albino rats were equally assigned to eight groups: one group receive no treatment, four groups were received CCl4-olive oil mixture [1:1(v/v)] (0.2ml/100g body weight (bw), intraperitoneally) two times/week for 4 weeks/rat alone or with 200mg Vit. C/kg bw or 5ml ASE/rat or both, and three groups received olive oil, Vit. C, or ASE. Vitamin C and ASE were orally administrated two weeks before CCl4 injection and 4 weeks concomitant with CCl4. Lipid peroxidation, lipogenesis-related genes, hepatic histopathology, Bax immunostaining and DNA fragmentation were assessed. ASE protected hepatic damage by suppressing oxidative stress and elevating activities of antioxidant enzymes, including superoxide dismutase and catalase. ASE also regulated hepatic dyslipidemia, hepatic lipid accumulation and expression of SREBP-1 and FAS genes in CCl4-treated rats. ASE decreased apoptosis through inhibition of CCl4 induced Bax activation in hepatocytes. These observations provide evidence for the hepatoprotective potential of ASE via inhibiting hepatic lipogenesis and oxidative stress, suggesting being used as a natural product in attenuating CCl4 induced oxidative damage, hepatotoxicity and associated dysfunction.

Evaluation of oxidative stress in seminal plasma of adolescents with varicocele.

SummaryVaricocele, defined by a dilation of efferent testicular veins, is the most commonly identifiable, surgically correctable lesion associated with male-factor infertility, starts at puberty and causes a progressive decline in fertility potential. The pathophysiology of infertility caused by this disease is still poorly understood, but it is suggested that the main mechanism is oxidative stress. Therefore, the aim of this study was to verify if the varicocele is associated with changes in enzymatic antioxidant mechanisms and seminal plasma lipid peroxidation levels in adolescents. We recruited 90 adolescents that were divided into control (C; n = 27); varicocele and normal semen (VNS; n =46); varicocele and altered semen (VAS; n =17). Seminal and serum levels of lipid peroxidation were quantified by thiobarbituric acid reactive substances (TBARS). Seminal plasma antioxidant profile was evaluated by the activities of catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). The VAS group had increased lipid peroxidation levels when compared to the other groups. The levels of serum lipid peroxidation and activities of the enzymes SOD and GPx did not differ between groups. CAT was undetectable by the method used. In conclusion, in adolescents with varicocele and altered semen analysis, there is an increase in seminal lipid peroxidation levels compared to adolescents with varicocele and without seminal change and adolescents without evident varicocele. However, the observed oxidative stress is not caused by a decrease in superoxide dismutase and glutathione peroxidase activities, which did not differ between adolescents with and without evident varicocele.Lay summaryVaricocele, defined by a dilation of efferent testicular veins, is the most commonly identifiable, surgically correctable lesion associated with male-factor infertility, starts at puberty and causes a progressive decline in fertile potential. There is still much that is not understood regarding how exactly it affects semen quality, but most studies agree that oxidative stress, which is defined as excessive amounts of free radicals in relation to antioxidant defense, is an important mechanism. In this study, we aimed to verify if the varicocele is associated with changes in antioxidant defense and semen oxidation in 90 adolescents with and without varicocele. In adolescents with varicocele and abnormal semen, there is an increase in semen oxidation compared to controls or to the group with varicocele and normal semen quality. Our results can help to understand how varicocele leads to infertility in adolescents, identifying changes in oxidative activity in semen, since the onset of varicocele and before damage to sperm production can be detected.

PENGARUH KOMBINASI EKSTRAK JERUK BRASTAGI DAN WORTEL PER ORAL SEBELUM AKTIVITAS FISIK TERHADAP PENURUNAN KADAR MDA PLASMA MENCIT SETELAH AKTIVITAS FISIK

Aerobic metabolism at the cellular level generates free radicals. Under normal conditions, there’s a balance between free radicals and endogenous antioxidants. An excessive amount of free radicals impair DNA, protein, fat, etc. The level of free radicals can be known by measuring plasma malondialdehyde level. Combination of Brastagi’s oranges and carrots juice as exogenous antioxidants supplementation expected to decrease free radicals level. The aim of this study is to investigate the difference of plasma MDA level during several time intervals on mice which are given and not given a combination of Brastagi’s oranges and carrots juice before physical activity using mice’s treadmill for 20 minutes. The research method used in this study is an experimental laboratory study. The objects of this study are 40 mice (mus musculus), white-colored, male, weighting 25-30 grams, which is randomly chosen. The objects are divided into 2 groups, Group A: 20 mice (given a combination of Brastagi’s oranges and carrots juice before physical activity using mice’s treadmill) and group B: 20 mice (not given a combination of Brastagi’s oranges and carrots juice before physical activity using mice’s treadmill). Group A is divided into 5 subgroups: A1 (measurement of plasma MDA level at 0 minutes after treadmill), A2 (measurement of plasma MDA level at 15 minutes after treadmill), and A3 (measurement of plasma MDA level at 30 minutes after treadmill), A4 (measurement of plasma MDA level at 60 minutes after treadmill), and A5 (measurement of plasma MDA level at 240 minutes after treadmill). The same procedures are employed for group B. Plasma MDA level measured after doing a physical activity using mice treadmill. The homogeneity of the result then was tested using Levene’s test and the normality of the result was tested using the Kolmogorov-Smirnov test (p>0.05). Further, the data were analyzed using an independent t-test (p≤0.05), one-way ANOVA (p≤0.05) then Duncan’s test were used. The results reveal significant lowering plasma MDA concentration in mice receiving a combination of Brastagi’s oranges and carrots juice before physical activity, which is measured during several time intervals: 0,15,30,60, and 240 minutes after physical activity than in mice not receiving a combination of Brastagi’s oranges and carrots juice before physical activity. The MDA level differences between groups that are given and not given combination of Brastagi’s orange and carrots juice before physical activity measured during several intervals are 11,44% (0,8920 vs 1,0071) measured 0 minutes after physical activity, 15,47% (0,7902 vs 0,9348) measured 15 minutes after physical activity, 14,42% (0,7473 vs 0,8732) measured 30 minutes after physical activity, 11,35% (0,6696 vs 0,7554) measured 60 minutes after physical activity, and 13,60% (0,5786 vs 0,6696) measured 240 minutes after physical activity.The conclusion of the study suggested that a combination of Brastagi’s orange and carrots juice supplementation has a lowering effect toward plasma MDA level measured during several time intervals.

Role of Edaravone as a Treatment Option for Patients with Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive and fatal neurodegenerative disease that leads to a loss of muscle control due to nerve cells being affected in the brain and spinal cord. Some of the common clinical presentations of ALS include weakness of muscles, changes in behavior, dysfunction in speech, and cognitive difficulties. The cause of ALS is uncertain, but through several studies, it is known that mutations in SOD1 or C9orf72 genes could play a role as a factor of ALS. In addition, studies indicate that an excessive amount of free radicals, the reactive oxygen species (ROS), leads to neuronal damage by the peroxidation of unsaturated fatty acids in the neuronal cells. Edaravone, the newly approved antioxidant drug for ALS, halts the progression of ALS in the early stages through its cytoprotective effect and protects the nerves by reducing ROS. In this review, different aspects of ALS will be discussed, including its pathology, genetic aspect, and diagnosis. This review also focuses on edaravone as a treatment option for ALS, its mechanism of action, and its pharmacological properties. Clinical trials and adverse effects of edaravone and care for ALS patient are also discussed.

Approaches and Methods to Measure Oxidative Stress in Clinical Samples: Research Applications in the Cancer Field.

Reactive oxygen species (ROS) are common by-products of normal aerobic cellular metabolism and play important physiological roles in intracellular cell signaling and homeostasis. The human body is equipped with antioxidant systems to regulate the levels of these free radicals and maintain proper physiological function. However, a condition known as oxidative stress (OS) occurs, when ROS overwhelm the body's ability to readily detoxify them. Excessive amounts of free radicals generated under OS conditions cause oxidative damage to proteins, lipids, and nucleic acids, severely compromising cell health and contributing to disease development, including cancer. Biomarkers of OS can therefore be exploited as important tools in the assessment of disease status in humans. In the present review, we discuss different approaches used for the evaluation of OS in clinical samples. The described methods are limited in their ability to reflect on OS only partially, revealing the need of more integrative approaches examining both pro- and antioxidant reactions with higher sensitivity to physiological/pathological alternations. We also provide an overview of recent findings of OS in patients with different types of cancer. Identification of OS biomarkers in clinical samples of cancer patients and defining their roles in carcinogenesis hold great promise in promoting the development of targeted therapeutic approaches and diagnostic strategies assessing disease status. However, considerable data variability across laboratories makes it difficult to draw general conclusions on the significance of these OS biomarkers. To our knowledge, no adequate comparison has yet been performed between different biomarkers and the methodologies used to measure them, making it difficult to conduct a meta-analysis of findings from different groups. A critical evaluation and adaptation of proposed methodologies available in the literature should therefore be undertaken, to enable the investigators to choose the most suitable procedure for each chosen biomarker.

Polyphenolic compounds of the stilbenoid class: classification, representatives, content in plant raw materials, structural features, use in the food industry and pharmacy

Nowadays, more than 300 representatives of stilbenoids are known - a group of natural, synthetic and semi-synthetic biologic active substances, according to the chemical structure belonging to the group of polyphenolic compounds - phenylpropanoids. Representatives of this group of compounds can be detected in such classes of plants as gymnosperms, angiosperms, bryophytes and pteridophyte. The main food sources are the fruits of grapes, blueberries, blueberries, peanuts, cocoa. The history of their detection is associated with the discovery of the protective functions of plants in response to the action of external stimuli. Further study revealed pronounced antioxidant properties. The mechanism of development of many diseases is associated with the processes of oxidation of free radicals, which can be interrupted by the effect of antioxidants. Possible mechanisms of antioxidant action of stilbenoids and their effect on diseases caused by excessive amounts of free radicals have been studied. Stilbenoids increase the tone and stability of the body to stress factors of the environment, improve the adaptive capacity of the nervous and immune systems, show antitumor, cardio-protective and lipid-lowering activities, inhibit lipid peroxidation. In this regard specialized products, food supplements and drugs containing stilbenoids have been developed. However, representatives of this group of compounds have low consumer properties, are sensitive to environmental factors and have low solubility and absorption. Therefore, solutions of these problems are important when developing new foods and drugs. Nowadays, auxiliary substances (solubilizers) are used, as well as such technological methods as microencapsulation, coacervation, polymerization, and others that can cope with problems of instability, poor solubility, low bioavailability, and unsatisfactory consumer qualities, which improve the effect of stilbenoids on the organism.

PENGARUH KOMBINASI EKSTRAK JERUK BRASTAGI DAN WORTEL PER ORAL SEBELUM AKTIVITAS FISIK TERHADAP PENURUNAN KADAR MDA PLASMA MENCIT SETELAH AKTIVITAS FISIK

Aerobic metabolism in the cellular level generates free radicals. Under normal condition,theres balance between free radicals and endogenous antioxidants. Excessive amount of freeradicals impair DNA, protein, fat, etc. The level of free radicals can be known by measuringplasma malondialdehyde level. Combination of Brastagis oranges and carrots juice asexogenous antioxidants supplementation expected to decrease free radicals level . The aim of thisstudy is to investigate the difference of plasma MDA level during several time intervals on micewhich is given and not given combination of Brastagis oranges and carrots juice before physicalactivity using mices treadmill for 20 minutes. The research method used in this study is anexperimental laboratory study. The objects of this study are 40 mice (mus musculus), whitecolored, male, weighting 25-30 grams, which is randomly chosen. The objects are divided into 2groups, Group A : 20 mice (given combination of Brastagis oranges and carrots juice beforephysical activity using mices treadmill) and group B : 20 mice (not given combination ofBrastagis oranges and carrots juice before physical activity using mices treadmill). Group Aare divided into 5 subgroups: A1 (measurement of plasma MDA level at 0 minute after treadmill),A2 (measurement of plasma MDA level at 15 minutes after treadmill), and A3 (measurement ofplasma MDA level at 30 minutes after treadmill), A4 (measurement of plasma MDA level at 60minutes after treadmill), and A5 (measurement of plasma MDA level at 240 minutes aftertreadmill). The same procedures are employed for the group B. Plasma MDA level measuredafter doing physical activity using mice treadmill. The homogenity of the result then was testedusing Levenes test and the normality of the result was tested using Kolmogorov-smirnov test (p>0.05). Further, the data was analyzed using independent t-test (p?0.05), one-way ANOVA(p?0.05) then Duncans test were used. The results reveal significant lowering plasma MDAconcentration in mice receiving combination of Brastagis oranges and carrots juice beforephysical activity, which is measured during several time intervals : 0,15,30,60, and 240 minutesafter physical activity than in mice not receiving combination of Brastagis oranges and carrotsjuice before physical activity. The MDA level differences between groups which is given and notgiven combination of Brastagis orange and carrots juice before physical activity measuredduring several intervals are 11,44% (0,8920 vs 1,0071) measured 0 minute after physical activity,15,47% (0,7902 vs 0,9348) measured 15 minutes after physical activity, 14,42% (0,7473 vs0,8732) measured 30 minutes after physical activity, 11,35% (0,6696 vs 0,7554) measured 60minutes after physical activity, and 13,60% (0,5786 vs 0,6696) measured 240 minutes afterphysical activity.The conclusion of the study suggested that combination of Brastagis orange andcarrots juice supplementation has lowering effect toward plasma MDA level measured duringseveral time intervals.

Activation of AMPK/Nrf2 signalling by Manuka honey protects human dermal fibroblasts against oxidative damage by improving antioxidant response and mitochondrial function promoting wound healing

Excessive amounts of free radicals are deleterious for cells, resulting in cell damage, affecting the wound healing process and causing premature ageing or even neoplastic transformation. Here the capacity of Manuka honey (MH) to protect against oxidative damage and improve the process of skin wound healing was investigated. Up to 16 compounds were identified in MH, with leptosin derivatives and methyl syringate as the major ones. MH protected against apoptosis, intracellular ROS production, and lipid and protein oxidative damage. MH also protected mitochondrial functionality, promoted cell proliferation and activated the AMPK/Nrf2/ARE signalling pathway, as well as the expression of the antioxidant enzymes such as SOD and CAT. Here we describe for the first time that one of the possible mechanisms by which MH exhibits its ability to promote wound healing could be due to its capacity to improve the antioxidant response by activating AMPK phosphorylation and the ARE response.

Edaravone leads to proteome changes indicative of neuronal cell protection in response to oxidative stress

Neuronal cell death, in neurodegenerative disorders, is mediated through a spectrum of biological processes. Excessive amounts of free radicals, such as reactive oxygen species (ROS), has detrimental effects on neurons leading to cell damage via peroxidation of unsaturated fatty acids in the cell membrane. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has been used for neurological recovery in several countries, including Japan and China, and it has been suggested that Edaravone may have cytoprotective effects in neurodegeneration. Edaravone protects nerve cells in the brain by reducing ROS and inhibiting apoptosis. To gain further insight into the cytoprotective effects of Edaravone against oxidative stress condition we have performed comparative two-dimensional gel electrophoresis (2DE)-based proteomic analyses on SH-SY5Y neuroblastoma cells exposed to oxidative stress and in combination with Edaravone. We showed that Edaravone can reverse the cytotoxic effects of H2O2 through its specific mechanism. We observed that oxidative stress changes metabolic pathways and cytoskeletal integrity. Edaravone seems to reverse the H2O2-mediated effects at both the cellular and protein level via induction of Peroxiredoxin-2.

Neutrophils: The Role of Oxidative and Nitrosative Stress in Health and Disease.

Neutrophils constitute the first line of the innate immunity in humans. They employ several strategies to trap and kill microorganisms, such as phagocytosis, degranulation, and the formation of extracellular traps (NETs). It has been well documented, that generation of reactive oxygen and nitrogen species (ROS and RNS) is crucial in the life cycle of a polymorphonuclear phagocyte. These compounds due to high reactivity act as powerful antimicrobial factors in the process of pathogens clearance and can also modulate immunological response. On the other hand, excessive amount of free radicals may have detrimental effect on host tissues and markers of oxidative and nitrosative stress are detectable in many diseases. It is necessary to maintain the balance between ROS/RNS formation and removal. The review highlights our current understanding of the role of ROS and RNS produced by neutrophils in health and disease.

The Effect of KIO3 and KI Salt Towards Iodium Levels (I2) in Urine, Malondialdehyde (MDA) and The Histology of Thyroid Gland of Goitrogenic Rat

Goitrogenic substances can inhibit of iodine taking by the thyroid gland. Thus iodine concentration in thyroid gland will be low, and this phenomena is indicated by inflammation in the thyroid gland. Moreover, it can cause releaseing of an excessive amount of free radicals. This radicals, in the body, causes oxidative stress and also increase the levels of malondialdehyde (MDA). This is also as an indicator for lipid peroxidation and the decreasing of urinary iodine excretion levels (EIU). The treatment with KIO 3 and KI salt was intended to study the level of supplementation of iodine (I 2 ) toward level of MDA in serum and histological description of rat’s thyroid gland. The MDA levels was determined through TBA test (Thio Barbituric Acid), meanwhile the histological pattern of rat thyroid gland was determined by Hematoxylen-Eosin staining (HE). The results indicated both of KIO 3 and KI salt significantly (p<0.01) reduced MDA level in the serum. Treatment with KIO 3 salt gave 33.62% while KI salt slightly higher (37,02%). In addition, both of treaments displayed an recovering effect in thyroid gland.

Role of free radicals and antioxidants in gynecological cancers: current status and future prospects

The potential role of free radicals and associated oxidative stress has been well documented in the development of many diseases. Free radicals are mainly derived from oxygen (reactive oxygen species, ROS) and nitrogen (reactive nitrogen species, RNS), under various physicochemical or pathological conditions. Excessive amount of free radicals eventually attack biomolecules including proteins, lipids and DNA, thus results in increased oxidative damage leads to alter the physiological functions of the cell and implicated in the activation of transcription factors and triggers a number of human diseases including carcinogenesis. Apart from many dietary components, mammalian cells have endowed with protective antioxidant defence system, which includes enzymatic (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) and non-enzymatic (glutathione, vitamin E (tocotrienols and tocopherols), vitamin C) antioxidants. The present review describes the role of the free radicals in the development of gynecological cancers and their key factors of the non-specific immune defence mechanism (antioxidants). The review also emphasizes the different potential applications of antioxidant/free radical manipulations in prevention and/or control of cancer. The novel and future approaches for better control of diseases are include gene therapy to produce more antioxidants, genetically engineered plant products with higher level of antioxidants, artificial antioxidant enzymes, novel biomolecules and the use of foods enriched with antioxidants.

The Third-Generation Beta-Blocker

In this issue of the Journal, Khan et al1 study the third-generation beta-blocker, nebivolol, in a rat model of aldosterone/salt treatment–induced hypertensive heart disease and show that myocyte necrosis is incited by oxidative stress secondary to an increase in cytosolic free calcium and mitochondrial calcium overload—a process that overwhelms the endogenous zinc (Zn)-based antioxidants. Using the first-generation beta-blocker atenolol as a control, treatment with nebivolol induced activation of endothelial nitric oxide synthase, nitric oxide (NO) generation, and a marked increase in intracellular Zn. Conversely, there was a concomitant decrease in intracellular and subsarcolemmal mitochondrial calcium levels. Likewise, there was attenuation of mitochondrial hydrogen peroxide production and lipid peroxidation, inhibition of microscopic myocardial scarring, and a reduction in collagen volume fractions. They postulate an intriguing pathophysiologic phenomenon whereby nebivolol, acting as a β3 agonist, increases NO formation leading to a rise in cytosolic free Zn. This inhibits intracellular and mitochondrial calcium overload, which ameliorates many of the detrimental effects of reactive oxygen species (ROS), lipid peroxidation, and the eventual myocardial scarring. Several important points can be gleaned from this study. First, this animal model of hypertensive cardiomyopathy serves as an effective model of sudden cardiac death as both myocardial fibrosis and adverse remodeling are key features of this disease process. This hypothesis, originally formulated by Weber and others, served as a fundamental basis for the RALES and EPHESUS trials. This concept was recently reviewed and confirmed by Esposito et al2 in a canine model of pacing-induced systolic heart failure, interstitial fibrosis, and myocardial electrical activation delays. They showed that mineralocorticoid receptor antagonism played a key role in preventing the activation of inflammatory pathways and in the development of ventricular arrhythmogenic foci. It is interesting to speculate that nebivolol may also induce similar cardioprotection. Nebivolol is approved for the treatment of hypertension in the United States and is marketed as Bystolic. In Europe, it is approved for the treatment of both hypertension and left ventricular failure. At low doses, it is a selective β1-receptor blocker, and as the dose is up-titrated, it loses its selectivity. It is unique in that unlike carvedilol (Coreg), it has a NO potentiating ability, a property that Khan et al1 have effectively shown in their study. Another plausible mechanism for the drug's efficacy is that it may act primarily within the mitochondria at the site of ROS production or as a ROS scavenger, inhibiting superoxide anion or hydrogen peroxide. Accordingly, the sequelae of pathology associated with excessive ROS production in hypertensive cardiomyopathy can effectively be targeted. Nebivolol is not the first beta-blocker to demonstrate antioxidant properties. Carvedilol, the first of the third-generation beta-blockers, has been shown in a number of studies to be both an antioxidant and free radical scavenger.3 Its antioxidant property resides in its carbazole moiety, a property partly shared by nebivolol. The apparent underlying protective mechanism of carvedilol is through inhibition of lipid peroxidation primarily through free radical scavenging. Khan et al1 showed that nebivolol could similarly protect against lipid peroxidation. This unique property has not received a great deal of attention from our clinical colleagues, except in the burgeoning field of Cardio-Oncology. The chemotherapeutic anthracyclines are known to be one of the most effective anticancer treatments available but produce an excessive amount of free radicals within the myocardium, leading to cardiotoxicity and heart failure. It is of no surprise then that carvedilol is currently considered the “beta-blocker of choice” for patients suffering from anthracycline-induced heart failure. Perhaps, it is time when nebivolol was investigated for its antioxidant properties in oxidative pathological conditions also? The use of the term “third-generation beta-blocker,” is a method we use to explain the hierarchy of beta-blockers in terms of development. Atenolol is a first-generation beta-blocker in terms of age, a drug known to have no antioxidant properties and a characteristic Khan et al1 use for control experiments. The second-generation beta-blockers include metoprolol, which although has cardioprotective effects, does not have any antioxidant effects. The current third-generation beta-blockers include carvedilol, a drug with antioxidant effects and free radical scavenging ability.4 Nebivolol can now be added to this list. It is rather interesting to recall that over the last several decades, both laboratory and clinical research with endogenous antioxidants such as superoxide dismutase, vitamin E, and catalase were all fraught with failure and frustration. Conceivably, the elusive and effective antioxidant has been right in front us for the past 20 years, and we were just a little slow in recognizing the potential expedient effects of these drugs.