Stress,Oxidative Injury and Disease

The living system on earth is largely using oxygen for burning metabolic fuel for energy. The toxicity of oxygen is largely due to the formation of free radicals in living systems. Stress is also responsible for the generation of free radicals. The evidence for the involvement of free radicals and oxidative injury in producing metabolic disturbance, maladjustment and many diseases has been accumulating since long. It is largely believed that the root cause of many chronic diseases is stress induced free radicals and resultant oxidative injury.     

Oxidative Stress and Skin Cancer: An Overview

Skin is the largest body organ that serves as an important environmental interface providing a protective envelope that is crucial for homeostasis. On the other hand, it is a major target for toxic insult by a broad spectrum of physical and chemical agents that are capable of altering its structure and function. There are a large number of dietary contaminants and drugs can manifest their toxicity in skin. These environmental toxicants or their metabolites are inherent oxidants and/or directly or indirectly drive the production of a variety of reactive oxidants also known as reactive oxygen species. These are short-lived entities that are continuously generated at low levels during the course of normal aerobic metabolism. These are believed to activate proliferative and cell survival signaling that can alter apoptotic pathways that may be involved in the pathogenesis of a number of skin disorders. The skin possesses an array of antioxidant defense mechanisms that interact with toxicants to obviate their deleterious effect. The “antioxidant power” of a food is an expression of its capability both to defend the human organism from the action of the free radicals and to prevent degenerative disorders. Plants like olive trees have their own built-in protection against the oxidative damage of the sun, and these built-in protectors function as cell protectors in our own body. Although many antioxidants have shown substantive efficacy in cell culture systems and in animal models of oxidant injury, unequivocal confirmation of their beneficial effects in human populations has proven elusive.     

Evaluation of Oxidative Stress and Antioxidant Status in Pregnant Anemic Women

The present study was conducted to investigate the oxidant–antioxidant status in iron deficient pregnant anemic women. One hundred thirty pregnant women with iron deficiency anemia (IDA) were divided into three groups, namely mild (50), moderate (50) and severe (30) anemic along with pregnant healthy women as controls (50). The complete blood count, plasma lipid peroxidation products, enzymatic and non-enzymatic antioxidants were measured according to respective protocols. The levels of complete blood count, iron, ferritin along with antioxidant enzymes namely catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and reduced glutathione were significantly reduced in all IDA groups. However, the level of oxidized glutathione, lipid peroxides, protein carbonyls, conjugated dienes were found significantly increased in all anemic patients. Antioxidant vitamins, namely C, E and A were also found significantly decreased in IDA patients. On the basis of our results, it may be concluded that IDA tends to increase the pro-oxidant components, which may result in various complications including peroxidation of vital body molecules resulting in increased risk for pregnant women as well as fetus.     

Evaluation of Oxidative Stress and hsCRP in Polycystic Ovarian Syndrome in a Tertiary Care Hospital

PCOS is a heterogeneous endocrine disorder with diverse clinical presentation. Oxidative stress plays a key role in the pathophysiology of this disease. Serumhigh sensitive C-reactive protein (hsCRP), a marker of chronic low grade inflammation, is indicative of future development of cardiovascular disease. Our aim is to evaluate the oxidant status and hsCRP levels in PCOS. The study involved 61 cases and 61 controls in the age group of 18–40 years diagnosed with PCOS. Erythrocyte malondialdehyde (MDA), superoxide dismutase (SOD), serum hsCRP, gonadotrophins, thyroid stimulating hormone, prolactin, glycemic status and lipid profile were estimated. Erythrocyte MDA (p < 0.001), SOD (p = 0.007) and serum hsCRP (p < 0.001) were significantly elevated in PCOS patients than controls. Oxidative stress is present in women with PCOS along with elevated hsCRP.     

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

The antioxidants are essential molecules in human system but are not miracle molecules. They are neither performance enhancers nor can prevent or cure diseases when taken in excess. Their supplemental value is debateable. In fact, many high quality clinical trials on antioxidant supplement have shown no effect or adverse outcomes ranging from morbidity to all cause mortality. Several Chochrane Meta-analysis and Markov Model techniques, which are presently best available statistical models to derive conclusive answers for comparing large number of trials, support these claims. Nevertheless none of these statistical techniques are flawless. Hence, more efforts are needed to develop perfect statistical model to analyze the pooled data and further double blind, placebo controlled interventional clinical trials, which are gold standard, should be implicitly conducted to get explicit answers. Superoxide dismutase (SOD), glutathione peroxidase and catalase are termed as primary antioxidants as these scavenge superoxide anion and hydrogen peroxide. All these three enzymes are inducible enzymes, thereby inherently meaning that body increases or decreases their activity as per requirement. Hence there is no need to attempt to manipulate their activity nor have such efforts been clinically useful. SOD administration has been tried in some conditions especially in cancer and myocardial infarction but has largely failed, probably because SOD is a large molecule and can not cross cell membrane. The dietary antioxidants, including nutrient antioxidants are chain breaking antioxidants and in tandem with enzyme antioxidants temper the reactive oxygen species (ROS) and reactive nitrogen species (RNS) within physiological limits. Since body is able to regulate its own requirements of enzyme antioxidants, the diet must provide adequate quantity of non-enzymic antioxidants to meet the normal requirements and provide protection in exigent condition. So far, there is no evidence that human tissues ever experience the torrent of reactive species and that in chronic conditions with mildly enhanced generation of reactive species, the body can meet them squarely if antioxidants defense system in tissues is biochemically optimized. We are not yet certain about optimal levels of antioxidants in tissues. Two ways have been used to assess them: first by dietary intake and second by measuring plasma levels. Lately determination of plasma/serum level of antioxidants is considered better index for diagnostic and prognostic purposes. The recommended levels for vitamin A, E and C and beta carotene are 2.2–2.8 μmol/l; 27.5–30 μmol/l; 40–50 μmol/l and 0.4–0.5 μmol/l, respectively. The requirement and recommended blood levels of other dietary antioxidants are not established. The resolved issues are (1) essential to scavenge excess of radical species (2) participants in redox homeostasis (3) selective antioxidants activity against radical species (4) there is no universal antioxidant and 5) therapeutic value in case of deficiency. The overarching issues are (1) therapeutic value as adjuvant therapy in management of diseases (2) supplemental value in developing population (3) selective interactivity of antioxidant in different tissues and on different substrates (4) quantitative contribution in redox balance (5) mechanisms of adverse action on excess supplementation (6) advantages and disadvantages of prooxidant behavior of antioxidants (7) behavior in cohorts with polymorphic differences (8) interaction and intervention in radiotherapy, diabetes and diabetic complications and cardiovascular diseases (9) preventive behavior in neurological disorders (10) benefits of non-nutrient dietary antioxidants (11) markers to assess optimized antioxidants status (12) assessment of benefits of supplementation in alcoholics and heavy smokers. The unresolved and intriguing issues are (1) many compounds such as vitamin A and many others possessing both antioxidant and non-antioxidant properties contribute to both the activities in vivo or exclusively only to non-antioxidant activity and (2) since human tissues do not experience the surge of FR, whether there is any need to develop stronger synthetic antioxidants. Theoretically such antioxidants may do more harm than good.     

Free Radical Status in Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is a major cause of blindness in children. Free radicals are implicated in the development of this retinopathy. We studied the role of free radicals in ROP and enrolled 60 preterm neonates at 30–32 weeks age. Thirty neonates predisposed to development of ROP, were placed in study group and 30 normal neonates in control group. Malondialdehyde and antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) were measured in blood spectrophotometrically. Both the groups were followed-up to 40–42 weeks age. Serum MDA levels, erythrocyte SOD and plasma GPX were significantly high in study group at 30–32 weeks as compared to control group. At follow up visit significant increase in MDA level and decrease in SOD and GPX level among the study group was seen. This disturbance in equilibrium of oxidant and antioxidant status initiates an inflammatory process in retinal tissue leading to development of ROP.     

Role of reactive oxygen species and antioxidants on pathophysiology of male reproduction

The excessive generation of reactive oxygen species (ROS) by abnormal spermatozoa and contaminating leukocytes has been defined as one of the few etiologies for male infertility. Administration of antioxidants in patients with ‘male factor’ infertility has begun to attract considerable interest. The main difficulty of such an approach is our incomplete understanding of the role of free radicals in normal and abnormal sperm function leading to male infertility. Mammalian spermatozoa membranes are very sensitive to free radical induced damage mediated by lipid peroxidation, as they are rich in polyunsaturated fatty acids. Limited endogenous mechanisms exist to reverse these damages. ROS attacks the fluidity of the sperm plasma membrane and the integrity of DNA in the sperm nucleus. ROS induced DNA damage accelerate the germ cell apoptosis. Unfortunately spermatozoa are unable to repair the damage induced by excessive ROS as they lack the cytoplasmic enzymes required to accomplish the repair. Assessment of such oxidative stress status (OSS) may help in the medical treatment. Treatment strategies must be directed toward lowering of ROS levels to keep only a small amount necessary to maintain normal cell function.     

Evaluation of Oxidative Stress and DNA Damage in Benign Prostatic Hyperplasia Patients and Comparison with Controls

In the present study, oxidative stress and lymphocytic DNA damage in both pre-op and post-op benign prostrate hyperplasia (BPH) patients with age >50 years was evaluated and compared with normal healthy subjects (controls- without any evidence of disease) of the same sex and age group. From December 2007 to November 2009, oxidative stress in 45 BPH patients were evaluated both before (pre-op patients) and after 7 days of surgery (post-op patients) in terms of measurements of plasma levels of (1) various anti-oxidative enzymes, (2) non-enzymatic antioxidants and (3) malondialdehyde which is a product of lipid peroxidation. The lymphocyte DNA damage was also evaluated by single cell alkaline gel electrophoresis in terms of tail length migration in these patients. These values were compared with their respective control subjects of similar sex and age group. The activities of antioxidant enzymes and the levels of antioxidant, reduced glutathione were found significantly decreased (p < 0.05) in serum samples of pre-operative group of BPH patients as compared to the controls. These altered parameters increased significantly (p < 0.05) and returned to their near normal control values, but not up to baseline values, in post operative patients i.e. after the cancer load was decreased by surgery. Lymphocytic DNA damage was found to be significantly increased in pre-op group as compared to controls and was reduced after surgery in post-op group. The present study therefore, shows significantly increased levels of oxidative stress and DNA damage in BPH patients which were reduced after removal of tumour load. Thus oxidative damage plays an important role in prostate tumourogenesis and timely management of oxidative stress can be of importance in preventing the occurrence of BPH.     

Oxidative stress and antioxidant status in normolipidemic AMI patients

The objective of the study was to observe the correlation between oxidative stress and antioxidants in myocardial infarct patients with normal lipid profile. In the present study investigation of lipid peroxidation and antioxidants were done in patients. This study was carried out on 165 AMI patients, (123 males and 42 females). The control group consisted on 165 normal healthy age-sex matched subjects (123 males and 42 females). Levels of Superoxide dismutase, Glutathione Peroxidase, Catalase, Malondialdehyde and Conjugated dienes were measured. The study found Superoxide dismutase, Glutathione Peroxidase, Catalase were significantly lower in activities (p<0.001) in AMI patients compared to controls. The markers of lipid peroxidation namely Malondialdehyde and Conjugated dienes were higher in AMI patients as compared to controls (p<0.001). The present study is clearly suggestive of increased oxidative stress in AMI patients. Oxidative stress appears as an etiological factor for myocardial infraction as a consequence the free radical scavengers levels are lowered in AMI patient.     

Oxidative stress and disturbance in antioxidant balance in beta thalassemia major

Repeated blood transfusion in beta thalassemia major patients may lead to peroxidative tissue injury by secondary iron overload. In the present study, 72 children with beta thalassemia major were included. Serum levels of total lipid peroxides, Iron, Total Iron Binding Capacity, Copper, Zinc, Vitamin E, plasma Total Antioxidant Capacity, activity of Erythrocyte Superoxide Dismutase, were measured. The findings were compared with 72 age matched healthy controls irrespective of sex. A significant increase in the levels of lipid peroxide and Iron (p<0.001), whereas, significant decrease in the levels of vitamin-E, Total Antioxidant Capacity and Total Iron Binding Capacity (p<0.001) was observed. Serum Zinc was significantly increased (p<0.001) with significant decrease in the levels of copper (p<0.001). Non Significant increase in the activity of Erythrocyte Superoxide Dismutase (p>0.05) was found in the patients when compared with controls. This suggest that oxidative stress and reduced antioxidant defense mechanism play an important role in pathogenesis of beta thalassemia major.     

Assessment of Oxidative DNA Damage by Alkaline Comet Assay in Human Essential Hypertension

The objective of the present study was to investigate the antioxidant status and the extent of oxidative DNA damage in lymphocytes and their relation with essential hypertension (EHT). A total of 100 South Indian subjects aged 30–65 were included for the study. Of these 50 were normotensive controls (group-1) with blood pressure ≥120/80 mm Hg, 50 were newly diagnosed (group-2) and were not on any antihypertensive drugs, but had systolic blood pressure ranging between 140 and 160 mmHg and diastolic blood pressure 95–100 mmHg and 50 newly diagnosed essential hypertensive patients underwent drug therapy for 1 year was considered as group-3. Enzymatic and non-enzymatic antioxidants significantly decreased and lymphocyte DNA damage was significantly increased in newly diagnosed hypertensive patients compared with control group. The major decrease in DNA damage and significant improvement in enzymatic and non-enzymatic antioxidants were observed after 1 year of antihypertensive therapy in treated group compared with newly diagnosed hypertensive patients. Total antioxidant status and lymphocyte DNA damage showed a strong negative correlation in all the three groups. Essential hypertension associated with oxidative stress which in turn causes genotoxic susceptibility to variety of disease including cancer. In the absence of DNA repair process and DNA checkpoint mechanisms, the genomic integrity is susceptible to extensive damage. In our study, increased oxidative DNA damage and decreased antioxidant levels were frequently observed in the newly diagnosed essential hypertensive patients, suggesting that oxidative stress is important in the pathogenesis of EHT. Therefore, the present study has additional clinical implication. Further investigations with large number of patients along with antioxidant supplement are highly warranted.     

Protective Role of <Emphasis Type="SmallCaps">l</Emphasis>-Arginine Against Free-Radical Mediated Oxidative Damage in Patients with Unstable Angina

Unstable angina is a critical condition of heart resulting from narrowing of vessels supplying blood to heart. Ischemia of the myocardium leads to oxidative stress and severe tissue damage. The objective of the present study was to determine the effect of l-arginine administration on the oxidant–antioxidant homeostasis which otherwise gets imbalanced in patients with cardiovascular diseases. The results obtained, show improvement in the oxidant–antioxidant levels of the subjects upon incorporation of l-arginine. Our findings suggest that supplementation of l-arginine along with regular anti-anginal therapy may be beneficial to the patients of unstable angina.     

Assessment of Oxidative Stress and Inflammatory Process in Patients of Multiple Myeloma

Multiple myeloma is a disseminated malignancy of monoclonal plasma cells that accounts for 15 % of all hematological cancers. The present study was conducted to evaluate the role of inflammation and oxidant-antioxidant dynamics in the etiology of this disease. The study population comprised of 20 cases of multiple myeloma and 20 healthy controls. The parameters evaluated were serum malondialdehyde (MDA), superoxide dismutase (SOD) and ferritin levels. The serum MDA levels were 1.9 ± 0.96 nmol/ml in cases as compared to 0.98 ± 0.55 nmol/ml in the controls. Similarly, a statistically significant difference was noted in the SOD and ferritin levels between the cases and controls (93.2 ± 23.8 vs. 210.1 ± 190.5 U/ml and 285.8 ± 216.4 vs. 131.8 ± 30.1 ng/ml respectively). Our study highlights the imbalance in the oxidant-anti oxidant mechanism and the role of smoldering inflammation in the etiology of multiple myeloma.     

Association of Elevated Serum Uric Acid with the Components of Metabolic Syndrome and Oxidative Stress in Abdominal Obesity Subjects

Abdominal obesity (AO) and metabolic syndrome (MetS) are associated with the cardiovascular disease and type 2 diabetes. Serum uric acid (SUA) is often elevated in subjects with the AO. We aimed to investigate the association of elevated SUA with the components of MetS, oxidative stress and TG/HDL-C ratio in AO subjects. This cross-sectional study used data from a Health Survey for Prevention of Hypertension and Type 2 Diabetes Mellitus in residents of two districts in Phitsanulok province, including 443 subjects. Anthropometric, blood pressure (BP) and biochemical variables were measured. We categorized the participants to two-group as 248 AO subjects (median age = 58, interquartile range 50.0–65.0 years) and 195 non-AO subjects (median age = 53, interquartile range 47.0–62.0 years). Waist circumference was significantly correlated with SystBP, DiastBP, Glu and SUA (P < 0.05) and SUA was significantly correlated with Glu, TG, HDL-C and TG/HDL-C ratio (P < 0.05). By using multiple logistic regression, we found the association of elevated SUA with abdominal obesity, hyperglycemia, hypertriglyceridemia, reduced HDL-C, elevated TG/HDL-C ratio, MetS and increased oxidative stress after adjusting for their covariates. Our study demonstrated that circulating UA is a major antioxidant and might help protect against free-radical oxidative damage. However, elevated SUA concentrations associated with oxidative stress, MetS, insulin resistance, and components of MetS. Then, SUA may be a marker of increased oxidative stress, insulin resistance and MetS, implying an increased risk of vascular disease and T2DM.     

Oxidative Stress-Induced Response of Some Endogenous Antioxidants in Schizophrenia

Reactive oxygen species (ROS) formed in various metabolic reactions cause unlimited damage by attacking and oxidizing the macromolecules. An arsenal of antioxidant substances neutralizes these ROS at various sites of their metabolic cascade, and if disequilibrium exists between the pro and antioxidant system, oxidative stress persists. The present study was undertaken in schizophrenia, to highlight the response and role of some endogenous antioxidants viz. reduced glutathione (GSH), bilirubin, total proteins, albumin and uric acid in scavenging the ROS. The effect of severity of disease, age factor, and substance abuse was also studied. In all, 50 schizophrenics and 50 age and sex-matched controls were enrolled in the present study. Fasting blood samples were drawn for estimating malondialdehyde (MDA), GSH, bilirubin, total proteins, albumin and uric acid in both the groups. The results were statistically analyzed by Z-test and correlated using correlation coefficient (r). The study shows reduction in MDA levels and decline in the level of endogenous antioxidants, but within the normal range. Chronic schizophrenics were at a higher risk of oxidative stress and age and substance abuse seems to worsen the situation.     

Changes in antioxidant enzyme levels and DNA damage during aging

Multiple mechanisms underlie the human aging process, but interest continues in the role that free radicals and antioxidants may play. The concentrations of lymphocyte free radical generation (O₂ ⁻& H₂O₂), DNA damage and antioxidant enzyme levels (glutathione Stransferase, superoxide dismutase and catalase) were evaluated in 110 healthy individuals with an age range of 20–80 years. The antioxidant enzyme levels were significantly less in very old age when compared to young. Moreover, the levels of free radical concentration and DNA damage were increased in the same age group with respect to younger group. Cigarette smoking had a positive relation with free radicals and DNA damage, and inverse relation with antioxidants. On the other hand, body mass was found to have positive relation with free radical generation only. The data indicate that depletion of antioxidant enzyme levels would render the older people more susceptible to free radical stress and DNA damage.     

Antioxidants: Basis concepts in relation to the eye

Antioxidants are a small group of substances that protect living cells from the destructive consequences of powerful oxidizing intermediates that can be formed from oxygen. Situations in which pro-oxidant mechanisms within the body are more active than the antioxidant mechanisms (oxidative stress) predispose and contribute to the pathogenesis of several ailments in various organs of the body. In the eye, pro-oxidant factors have been blamed for the causation of diseases such as age related macular degeneration and senile cataract. The role of pro-oxidants in the genesis of certain diseases is well established however, the effectivity of antioxidants provided to the body by dietary supplementation is inconclusive. In this article we provide a review on the basic concepts of antioxidant-pro-oxidant interaction in relation to its effects on the eye.     

Assessment of Some Biochemical Oxidative Stress Markers in Male Smokers with Chronic Periodontitis

The present study aims to assess and compare the biochemical oxidative stress markers in male smokers and non-smokers with chronic periodontitis. One hundred thirty-four male chronic periodontitis patients and 64 apparently healthy male volunteers were recruited for the study. The periodontal status was evaluated by measuring gingival index, plaque index, papillary bleeding index and clinical attachment loss using UNC-15 probe. The biochemical markers estimated were total antioxidant capacity, RBC-superoxide dismutase, glutathione peroxidase, vitamin C, malondialdehyde and C-reactive protein. The obtained results indicate higher oxidative stress in chronic periodontitis. Smokers with chronic periodontitis show significantly higher periodontal clinical parameters and relatively higher systemic oxidative stress. Vitamin C estimation may be an important biochemical parameter in conjunction with clinical parameters for diagnosis of chronic periodontitis in smokers.     

Role of Oxidative Stress in Various Stages of Psoriasis

Psoriasis is a chronic inflammatory, proliferative skin disease characterized by pathological skin lesions due to various exogenous and endogenous factors. It is associated with a number of biochemical and immunological disturbances. Recently, it has been suggested that increased reactive oxygen species (ROS) production and compromised function of antioxidant system may be involved in the pathogenesis of this disease. In the present study, 90 psoriasis patients were selected. Disease severity was assessed by psoriasis area severity index score and grouped as mild, moderate and severe (each group consists of 30 subjects) and compared with 30 healthy controls. Serum levels of malondialdehyde, nitric oxide end products and the activities of antioxidant enzymes such as erythrocyte-superoxide dismutase, catalase and total antioxidant status were investigated in these groups/subjects. As compared to controls, we found severitywise significantly increased serum malondialdehyde, nitric oxide end products with decrease in erythrocyte-superoxide dismutase activity, catalase activity and total antioxidant status in patients with psoriasis suggesting worsening of the disease. It seems to be linked with the enhancement of Reactive Oxygen Species production and decreased antioxidant potential in psoriasis.     

Oxidative stress and antioxidant status in patients with chronic myeloid leukemia

Chronic myeloid leukemia is a myeloproliferative disorder with a unique rearrangement, the Philadelphia chromosome. Oxidative stress, a pervasive condition of an increased number of reactive oxygen species, is now recognized to be prominent feature of various diseases and their progression. Thus antioxidants, which control the oxidative stress state, represent a major line of defense regulating overall true state of health. The relationship between antioxidants status and levels of well-known markers of oxidative stress that are measured as lipid peroxides and oxidized proteins reflect better health indices and postures. The aim of this study was to evaluate the role of oxidative stress in pathophysiology of Chronic myeloid leukemia by measuring the circulating plasma lipid peroxide levels in terms of malonyldialdehyde, total lipid hydroperoxide and oxidized proteins as protein carbonyl whereas antioxidant status were estimated in terms of reduced glutathione and total thiol in plasma of Chronic myeloid leukemia patients. The present study included 47 Chronic myeloid leukemia patients and 20 age-and sex-matched healthy subjects. Out of 47 Chronic myeloid leukemia patients, 31 were in chronic phase (CML-CP) and 16 in accelerated phase (CML-AP). The median age of Chronic myeloid leukemia patients was 33 years and that of controls was 32 years. Oxidative stress and antioxidant status in plasma were evaluated by spectrophotometric procedures. There was a significant increase (p<0.05) in plasma malonyldialdehyde, total lipid hydroperoxide and protein carbonyl levels in Chronic myeloid leukemia patients as compared to healthy subjects. Our results also showed that plasma malonyldialdehyde and protein carbonyl levels were markedly elevated (p<0.05) in both chronic phase (CML-CP) and accelerated phase (CML-AP) as compared to healthy volunteers. Antioxidant status was found to be significantly decreased (p<0.05) in Chronic myeloid leukemia patients and its phases as compared to healthy participants. It could be concluded that oxidative stress may be associated with the pathophysiology of Chronic myeloid leukemia.