Excessive Free Radical Generation Research Articles

Mitochondrial Dysfunction as the Major Basis of Brain Aging.

The changes in the properties of three biological events that occur with cerebral aging are discussed. These adverse changes already begin to develop early in mid-life and gradually become more pronounced with senescence. Essentially, they are reflections of the progressive decline in effectiveness of key processes, resulting in the deviation of essential biochemical trajectories to ineffective and ultimately harmful variants of these programs. The emphasis of this review is the major role played by the mitochondria in the transition of these three important processes toward more deleterious variants as brain aging proceeds. The immune system: the shift away from an efficient immune response to a more unfocused, continuing inflammatory condition. Such a state is both ineffective and harmful. Reactive oxygen species are important intracellular signaling systems. Additionally, microglial phagocytic activity utilizing short lived reactive oxygen species contribute to the removal of aberrant or dead cells and bacteria. These processes are transformed into an excessive, untargeted, and persistent generation of pro-oxidant free radicals (oxidative stress). The normal efficient neural transmission is modified to a state of undirected, chronic low-level excitatory activity. Each of these changes is characterized by the occurrence of continuous activity that is inefficient and diffused. The signal/noise ratio of several critical biological events is thus reduced as beneficial responses are gradually replaced by their impaired and deleterious variants.

Why do we age? The main signs of aging

Aging is a gradual and irreversible pathophysiological process. This is manifested in the decline of tissue and cell functions and a significant variety of pathologies associated with aging, including neurodegenerative diseases, cardiovascular diseases, metabolic disorders, increased risk of diseases of the skeleton and the immune system. Although modern medical advances have made a certain contribution to human health and greatly extended life expectancy, along with the aging of society, various chronic diseases are gradually emerging, which are the most important causes of disability and death of the elderly. Aim. The aim of the work is to analyze modern ideas in the field of causes and manifestations of aging processes for the possibility of developing a strategy to slow down its course. At the molecular and cellular level, aging is a complex biological process involving the gradual deterioration of various cellular and molecular processes in the body over time. The length of a person’s life is closely related to the decrease in the possibilities of repair and regeneration of tissues and organs. In response to stress at the molecular, cellular, and systemic levels, genetic, epigenetic, and environmental regulatory factors cause a decrease in the body’s physiological capabilities. They use complex molecular mechanisms that together contribute to aging. Molecular mechanisms (such as telomere shortening, accumulation of DNA damage, metabolic changes, and excessive free radical generation) strongly link various factors to the rate of aging. Collectively, these mechanisms inhibit cell proliferation, alter metabolism and gene expression, and induce high levels of free radicals, maintaining a senescent cell phenotype. Although the number of early senescent cells is low, they can limit the regenerative capacity of tissue stem cells and lead to the accumulation of cellular damage, thereby contributing to age-related diseases. Conclusions. Current advances in high-throughput genomics, transcriptomics, proteomics, and metabolomics enable the characterization and quantification of thousands of epigenetic markers, transcripts, proteins, metabolites, and can reveal general changes that occur with age in complex organisms at the molecular level. Thus, the integration of these molecular markers and related molecular mechanisms into a comprehensive assessment of biological age to prevent age-related functional decline and morbidity is becoming an increasingly pressing issue in medical science and should be implemented in practice as soon as possible.

Magnesium and the Hallmarks of Aging.

Magnesium is an essential ion in the human body that regulates numerous physiological and pathological processes. Magnesium deficiency is very common in old age. Age-related chronic diseases and the aging process itself are frequently associated with low-grade chronic inflammation, called 'inflammaging'. Because chronic magnesium insufficiency has been linked to excessive generation of inflammatory markers and free radicals, inducing a chronic inflammatory state, we formerly hypothesized that magnesium inadequacy may be considered among the intermediaries helping us explain the link between inflammaging and aging-associated diseases. We show in this review evidence of the relationship of magnesium with all the hallmarks of aging (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, disabled autophagy, dysbiosis, and chronic inflammation), which may positively affect the human healthspan. It is feasible to hypothesize that maintaining an optimal balance of magnesium during one's life course may turn out to be a safe and economical strategy contributing to the promotion of healthy aging. Future well-designed studies are necessary to further explore this hypothesis.

Flavonoids - A Review on Natural Antioxidants

As a result of the modern lifestyle, which includes processed foods, exposure to a large number of toxins and a lack of exercise oxidative stress is induced, due to which free radical production happens continually in all cells as part of normal cellular activity. Excess free radical generation, which can come from a variety of endogenous or exogenous sources, is thought to have a role in the ageing process and the development of illnesses. High levels of reactive oxygen species, on the other hand, destroy lipids, proteins, and DNA by blocking, scavenging, or accelerating their breakdown. Consumer concerns about the safety of their health have prompted the food sector to look for natural alternatives to manufactured equivalents. So now antioxidant capabilities of medicinal plants are being utilised for their capacity to treat or prevent a variety of human illnesses, one of which appears to be oxidative stress. Flavonoids are a class of polyphenol secondary metabolite which serves as a natural antioxidant and is present in a variety of plants and diets. Antiviral, anti-inflammatory, cardioprotective, anti-diabetic, anti-cancer, anti-aging, and other bioactive qualities are known to exist in them. Flavonoids are the topic of this review, including their varieties and sources, structural characteristics, and therapeutic implications.

Analysis of the Prognostic Potential of Schlafen 11, Programmed Death Ligand 1, and Redox Status in Colorectal Cancer Patients.

The Schlafen 11 (SLFN11) protein has recently emerged as pivotal in DNA damage conditions, with predictive potential for tumor response to cytotoxic chemotherapies. Recent discoveries also showed that the programmed death ligand 1 (PD-L1) protein can be found on malignant cells, providing an immune evasion mechanism exploited by different tumors. Additionally, excessive generation of free radicals, redox imbalance, and consequential DNA damage can affect intestinal cell homeostasis and lead to neoplastic transformation. Therefore, our study aimed to investigate the significance of SLFN11 and PD-L1 proteins and redox status parameters as prognostic biomarkers in CRC patients. This study included a total of 155 CRC patients. SLFN11 and PD-L1 serum levels were measured with ELISA and evaluated based on redox status parameters, sociodemographic and clinical characteristics, and survival. The following redox status parameters were investigated: spectrophotometrically measured superoxide dismutase (SOD), sulfhydryl (SH) groups, advanced oxidation protein products (AOPP), malondialdehyde (MDA), pro-oxidant-antioxidant balance (PAB), and superoxide anion (O2•-). The prooxidative score, antioxidative score, and OXY-SCORE were also calculated. The results showed significantly shorter survival in patients with higher OXY-SCOREs and higher levels of serum SLFN11, while only histopathology-analysis-related factors showed significant prognostic value. OXY-SCORE and SLFN11 levels may harbor prognostic potential in CRC patients.

Effect of extraction temperature on the phytochemicals, minerals and antioxidant properties of<em> Telfairia occidentalis</em> leaf extracts

Telfairia occidentalis leaves are known to possess many therapeutic potentials such as antidiabetic, anti-inflammatory, anticholesterolemic etc. To maximize their use in phytomedicine, the conditions used in preparation methods are crucial. Therefore, this study estimated the effect of extraction temperature on the phytochemicals, minerals, and antioxidant properties of T. occidentalis leaves. The powdered samples of T. occidentalis leaves were extracted using water at 1000C and 250C, respectively, followed by the phytochemical, mineral and antioxidant analyses of the plant extracts. The concentration of most constituent metabolites in the cold extract of T. occidentalis leaves was significantly (p < 0.05) higher than that of the hot extract. The highest mineral concentrations in hot and cold extracts of T. occidentalis leaves were sodium (2.22 mg/L) and potassium (2.77 mg/L), respectively. In the antioxidant study, the EC50 values (131.20 ± 1.70 μg/ml and 105.08 ± 0.54 μg/ml) of the hot extract of T. occidentalis leaves were significantly (p < 0.05) lower than those of the cold extract (228.17 ± 23.03 μg/ml and 151.47 ± 14.68 μg/ml). The study reveals that the extracts hold varying biological importance. The cold aqueous extract can be an excellent nutritional adjuvant for the supply of essential nutrients, whereas the hot aqueous extract can act as an important agent in ameliorating pathological conditions thrive on excessive free radical generation. Therefore, the different extraction procedures can be utilized based on the desired biological outcome.

Indices of Inflammation, Oxidative Stress and DNA damage in T2DM patients with and without Insulin Therapy

Background: Type 2 Diabetes Mellitus is a metabolic disorder associated with excessive free radical generation and oxidative stress. Pharmacological interventions of T2DM targets on glycemic control and reduce the circulatory levels of oxidative stress and inflammation. Aim: The study compared the levels of oxidative stress, inflammation and the extent of DNA damage in T2DM patients undergoing different treatment modalities. Methods: 150 subjects recruited for this study belonged to the age group of 35-65 years. Participants were grouped as healthy controls (n=50), diabetics treated with oral hypoglycemic agent metformin (n=50) and diabetics undergoing combined therapy of insulin and metformin (n = 50). All the participants underwent the assessment of anthropometric measures, baseline blood pressure and blood samples were analysed for FBS, HbA1c, MDA, TAC, Hs-CRP and DNA damage. Results: Analysis using one-way ANOVA showed that despite the same age and duration of T2DM, patients in insulin therapy group had significantly higher levels of oxidative stress, inflammation and DNA damage when compared to T2DM patients treated with metformin alone. Further, significant correlations were observed for the above parameters with the duration of T2DM.Conclusion: The study concludes that oxidative stress, systemic inflammation and cellular senescence are more prominent in T2DM patients undergoing insulin therapy. Poor glycemic control observed in these patients could be attributed to increased insulin resistance as a consequence of oxidative stress and inflammation.

Ginger or Black Pepper Supplements Attenuate Oxidative stress and Renal Damage in Metabolic Syndrome-induced Wistar Rats

There has been an increasing occurrence of cardio-metabolic risk factors globally due to increasing consumption of fructosesweetened foods and drinks that cause excessive generation of free radicals. This research investigated the inclusion of ginger and black pepper in the diet as an easy and affordable means of managing oxidative stress and kidney damage in metabolic syndrome-induced rats. Fifteen metabolic syndrome-induced rats were divided into three groups and fed on diets supplemented with 2 % inclusions of ginger or black pepper. Serum activities of antioxidant enzymes and some indices of renal functions were determined. Compared with the normal control, there were significantly (p<0.05) lower activities of all the studied antioxidant enzymes (Superoxide dismutase, Glutathione peroxidase, Catalase, and glutathione reductase) in the groups of metabolic syndrome induced-rats fed ginger or black pepper-supplemented diets which had significantly higher activities of these enzymes if compared with the group of metabolic syndrome- induced rats fed standard diets. The serum concentrations of malondialdehyde in all the groups of metabolic syndrome-induced rats fed the spices-supplemented diets did not significantly (p>0.05) differ from the concentration in the control group. The groups of metabolic-syndrome-induced rats fed ginger or black pepper-supplemented diets had significantly (p<0.05) higher concentrations of urea, uric acid, and creatinine in comparison with the normal control, but significantly (p<0.05) lower concentrations of these metabolites if compared with the metabolic syndrome-induced rats fed a standard diet. Similarly, the concentrations of serum electrolytes were significantly higher (p<0.05) in the groups of metabolic-syndrome-induced rats fed spices-supplemented diets compared with the normal control. From the findings, it is concluded that including ginger or black pepper in diets could be useful in managing oxidative stress and kidney dysfunction resulting from the consumption of metabolic syndrome-causing diets.

Investigation of the Protective Effects of Urtica dioica, Capsella bursa-pastoris and Inula racemosa on Acetaminophen-Induced Nephrotoxicity in Swiss Albino Male Mice

Acetaminophen (APAP) is the most commonly used nonprescription antipyretic-analgesic drug. This medication is thought to be safe at the suggested dosage (4 g/24 h), but its overdose (up to 2.5 g/kg) can cause severe injuries to the human body, including renal injury. APAP has various toxic effects on nephrons, as it leads to an excessive free radical generation that, in turn, results in a disturbance in the redox homeostasis of cells, causing oxidative stress. To replenish this oxidative stress, there is an ultimate urge for natural therapies that can retain the cellular homeostasis of nephrons by diminishing the overdose impression of acetaminophen. The principle objective of this work is to appraise nephrotoxicity due to APAP and its amelioration through the antioxidant properties of aqueous extracts of selected medicinal plants: Urtica dioica, Capsella bursa-pastoris, and Inula racemosa (UD, CBP, and IR, respectively). The pH stability of the nutraceuticals used was examined by determining the impact of pH 4, pH 7 and pH 9 on the DPPH radical scavenging activity of aqueous plant extracts. Gas chromatography-Mass spectroscopy (GC–MS) analytical technique was performed to determine the volatile organic phytochemical profiles of all three medicinal plants. Male Swiss albino mice were used for the present investigation. The animals were distributed into five groups of (n = 6), a total of 30 mice, for in vivo analysis. Group 1 served as the control group; group 2 received a single IP dose of APAP (600 mg/kg); group 3 received APAP pretreated with UD (300 mg/kg); group 4 received APAP pretreated with CBP (300 mg/kg); and group 5 received APAP pretreated with IR (300 mg/kg). Overdose of the APAP- induced a significant (p < 0.05) alterations in the total protein concentration, weight and the nephrological architecture in renal tissue, as observed through biochemical assays and histopathological examinations. Due to nephrotoxicity, there was a substantial (p < 0.05) drop in body weight and total protein contents in the APAP alone group when compared to the treatment groups. There was remarkable protection against APAP-induced alterations in the total protein of renal homogenate in the treatment groups. Histopathological analysis (H&E staining) of the mice kidneys indicated severe deterioration in the APAP alone group, whereas the therapy groups showed considerable nephroprotection towards APAP-induced abnormalities. The biochemical findings and histopathological study of the kidneys revealed that the herbal extracts (UD, CBP, and IR) have a nephroprotective potential against APAP-induced nephropathy. The trend of efficacy was observed as UD > CBP > IR. However, extensive study is needed to determine the likely ameliorative mechanism of these nutraceuticals.

The Impact of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and highly fatal neurodegenerative disease. Although the pathogenesis of ALS remains unclear, increasing evidence suggests that a key contributing factor is mitochondrial dysfunction. Mitochondria are organelles in eukaryotic cells responsible for bioenergy production, cellular metabolism, signal transduction, calcium homeostasis, and immune responses and the stability of their function plays a crucial role in neurons. A single disorder or defect in mitochondrial function can lead to pathological changes in cells, such as an impaired calcium buffer period, excessive generation of free radicals, increased mitochondrial membrane permeability, and oxidative stress (OS). Recent research has also shown that these mitochondrial dysfunctions are also associated with pathological changes in ALS and are believed to be commonly involved in the pathogenesis of the disease. This article reviews the latest research on mitochondrial dysfunction and its impact on the progression of ALS, with specific attention to the potential of novel therapeutic strategies targeting mitochondrial dysfunction.

Modulatory effect of Luteolin on potassium dichromate‐induced nephrotoxicity, cardiotoxicity and genotoxicity via Kim‐1/Nrf2 signaling pathways

Environmental and occupational exposure to chromium compounds has become a potential aetiologic agent for kidney disease through excessive generation of free radicals, induction of apoptosis and exaggerated inflammatory responses. These are some pathophysiologic mechanisms of potassium dichromate (K2Cr2O7) toxicity with attendant nephrotoxicity and cardiotoxicity. The cardioprotective and nephroprotective effects of Luteolin, a known potent antioxidant were evaluated in this study as described; Group A (normal saline), Groups B (30 mg/kg K2Cr2O7), Group C (Luteolin 100 mg/kg and K2Cr2O7 30 mg/kg), and Group D (Luteolin 200 mg/kg and K2Cr2O7 30 mg/kg), respectively.Markers of antioxidant defense system, oxidative stress, blood pressure and micronucleated polychromatic erythrocytes (MnPEs) were determined. Immunohistochemistry of Kidney Injury molecule (Kim‐1), nuclear factor erythroid 2‐related factor 2 (Nrf2), and cardiac troponin I (CTnI) were also determined.Our results showed that administration of K2Cr2O7increased systolic, diastolic and mean arterial blood pressures, markers of oxidative stress, the frequency of micronucleated polychromatic erythrocytes together with a significant reduction in serum nitric oxide bioavailability.Immunohistochemical staining revealed higher expression of renal Kim‐1 and cardiac troponin I in rats intoxicated with K2Cr2O7. However, lower expression of renal and cardiac Nrf2 were also observed in Luteolin co‐administered rats. Furthermore, co‐treatment with Luteolin restored blood pressure parameters, with concomitant reduction in oxidative stress indicators, augmented in vivo antioxidant status and improved serum NO levels. Lowered expressions of Kim‐1, CTnI and up‐regulation of both cardiac and renal Nrf2, and reduced frequency of micronucleated polychromatic. Taken together, this study demonstrates for the first time the antihypertensive, cardioprotective, nephroprotective and antigenotoxic effects of Luteolin against potassium dichromate induced‐toxicity through antioxidant and radical scavenging mechanisms.

Flow reactor for preparation of lipid nanoparticles via temperature variations

Lipid nanoemulsions and nanosuspensions are used as flavor carriers and bubble stabilizers in soft drinks and foods, as well as delivery vehicles for lipophilic drugs in pharmaceutics. Common techniques for their formation are the high-pressure and ultrasonic homogenizers. These techniques dissipate most of the input energy, which results in excessive heating and generation of free radicals that might modify sensitive ingredients. Low energy methods are also used in some applications, but they have specific limitations restricting their universal use. In the current study, we propose an alternative approach - a flow reactor with a variable temperature, which utilizes the lipids' polymorphic transitions to induce spontaneous fragmentation of the lipid microparticles into nanoparticles. The reactor allows us to obtain emulsions or suspensions with particle diameters tunable between 20 and 800 nm when appropriate surfactants, temperature profiles, and flow rates are applied. The fragmentation is comparable to that in a high-pressure homogenizer at ca. 500 bars or higher, without creating emulsion overheating or cavitation typical for the conventional methods. The flow reactor can be scaled up to industrial applications using simple scaling rules.

Targeting COPD with PLGA-Based Nanoparticles: Current Status and Prospects.

Chronic obstructive pulmonary disease (COPD) is pulmonary emphysema characterized by blockage in the airflow resulting in the long-term breathing problem, hence a major cause of mortality worldwide. Excessive generation of free radicals and the development of chronic inflammation are the major two episodes underlying the pathogenesis of COPD. Currently used drugs targeting these episodes including anti-inflammatory, antioxidants, and corticosteroids are unsafe, require high doses, and pose serious side effects. Nanomaterial-conjugated drugs have shown promising therapeutic potential against different respiratory diseases as they are required in small quantities which lower overall treatment costs and can be effectively targeted to diseased tissue microenvironment hence having minimal side effects. Poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) are safe as their breakdown products are easily metabolized in the body. Drugs loaded on the PLGA NPs have been shown to be promising agents as anticancer, antimicrobial, antioxidants, and anti-inflammatory. Surface modification of PLGA NPs can further improve their mechanical properties, drug loading potential, and pharmacological activities. In the present review, we have presented a brief insight into the pathophysiological mechanism underlying COPD and highlighted the role, potential, and current status of PLGA NPs loaded with drugs in the therapy of COPD.

Computational Investigation of the Antioxidant Activity of Dihydroxybenzoic Acids in Aqueous and Lipid Media

Reactive free radicals have both beneficial and destructive effects. Indeed, at physiological levels, free radicals help to preserve homeostasis by acting as signal transducers. However, excessive generation of free radicals can harm and damage membranes, proteins, and DNA, among other cell structures. Dihydroxybenzoic acids (DHBAs) have proven their antioxidant capacity against a large variety of free radicals, as well as their ability to inhibit or restrict reactive species overproduction. In this paper, a computational analysis of the antioxidant activity of a series of DHBAs in polar and nonpolar media was carried out at the DFT/M06-2X/6-[Formula: see text] level of theory. The implicit SMD solvation model was used in order to rationalize the experimental findings and to investigate the solvent effect on the mechanism and the radical scavenging ability. The obtained results put in evidence that HAT is the predominant mechanism in nonpolar media, whereas SPLET is more favored in polar environment. The BDE[Formula: see text], [Formula: see text], and [Formula: see text] descriptors are used to predict the most reactive hydroxyl groups and the antioxidant activity order of the studied DHBAs. Our results are in total agreement with experimental findings (inhibition of lipid peroxidation and scavenging of hydrogen peroxide). Moreover, this study shows that the substitution of the hydrogen atom by strong electron-donating groups, namely NMe2, in the ortho positions of the best experimental DHBAs leads to a significant enhancement of their antioxidant activity.

Melatonin Alleviates Constant Light Induced Oxidative Stress Damages of Kidney and Spleen of Female Rat

Photoperiod refers to the relative duration of light and dark that an animal experiences over the course of a 24 h period. Light is the principal stimulus that causes profound physiological and behavioural changes in all living organism. By manipulating photoperiod, melatonin production changes and its secretion drives enduring changes in many physiological systems of our body. Taking into consideration that light can affect pineal function and melatonin can be used as reactive oxygen species scavenger, act as a potent antioxidant and immunomodulator in mammals, the present experiment was designed and conducted to explore the consequences of constant light exposure on oxidative stress and antioxidant status on kidney and spleen of rat. 16 young adult female rats were randomly divided into 3 groups. The 4 rats of first group were employed as Control. These animals were kept under a 12 h light (600 lux, 60 days)/12 h dark cycle. The 8 rats of second group were maintained under constant light condition (600 lux, 60 days). After 60 days of constant light exposure second group of rats were randomly divided into two. One of these group of rats were designated as constant light exposed rats (LL) and another group of rats exposed to constant light is treated with melatonin (LL+MEL) for 21 days. The 4 rats of third group were only supplemented melatonin (MEL). The results showed that constant light exposure (60 days, 600 lux) resulted in an increased lipid peroxidation rate in kidney and spleen tissue and could effectively disturb the immune cells function through excessive generation of free radicals and decreased antioxidant enzymes activity (superoxide dismutase, catalase, glutathione peroxidase) through physiological or functional pinealectomy. Exogenous melatonin administration (200 µg/100 g body weight/day) suppressed the constant light induced oxidative stress and increase the activity of antioxidant enzymes in kidney and spleen of rat. Hence, melatonin has a nephroprotective and immunoprotective effects following photoperiodic stress induced cellular damages in female rat model.

Free radical biology in neurological manifestations: mechanisms to therapeutics interventions.

Recent advancements and growing attention about free radicals (ROS) and redox signaling enable the scientific fraternity to consider their involvement in the pathophysiology of inflammatory diseases, metabolic disorders, and neurological defects. Free radicals increase the concentration of reactive oxygen and nitrogen species in the biological system through different endogenous sources and thus increased the overall oxidative stress. An increase in oxidative stress causes cell death through different signaling mechanisms such as mitochondrial impairment, cell-cycle arrest, DNA damage response, inflammation, negative regulation of protein, and lipid peroxidation. Thus, an appropriate balance between free radicals and antioxidants becomes crucial to maintain physiological function. Since the 1brain requires high oxygen for its functioning, it is highly vulnerable to free radical generation and enhanced ROS in the brain adversely affects axonal regeneration and synaptic plasticity, which results in neuronal cell death. In addition, increased ROS in the brain alters various signaling pathways such as apoptosis, autophagy, inflammation and microglial activation, DNA damage response, and cell-cycle arrest, leading to memory and learning defects. Mounting evidence suggests the potential involvement of micro-RNAs, circular-RNAs, natural and dietary compounds, synthetic inhibitors, and heat-shock proteins as therapeutic agents to combat neurological diseases. Herein, we explain the mechanism of free radical generation and its role in mitochondrial, protein, and lipid peroxidation biology. Further, we discuss the negative role of free radicals in synaptic plasticity and axonal regeneration through the modulation of various signaling molecules and also in the involvement of free radicals in various neurological diseases and their potential therapeutic approaches. The primary cause of free radical generation is drug overdosing, industrial air pollution, toxic heavy metals, ionizing radiation, smoking, alcohol, pesticides, and ultraviolet radiation. Excessive generation of free radicals inside the cell R1Q1 increases reactive oxygen and nitrogen species, which causes oxidative damage. An increase in oxidative damage alters different cellular pathways and processes such as mitochondrial impairment, DNA damage response, cell cycle arrest, and inflammatory response, leading to pathogenesis and progression of neurodegenerative disease other neurological defects.

Luteolin mitigates potassium dichromate-induced nephrotoxicity, cardiotoxicity and genotoxicity through modulation of Kim-1/Nrf2 signaling pathways.

Environmental and occupational exposure to chromium compounds has become potential aetiologic agent for kidney disease with excessive generation of free radicals, apoptosis, and inflammatory. These pathophysiologic mechanisms of potassium dichromate (K2 Cr2 O7 ) have been well correlated with nephrotoxicity and cardiotoxicity. The cardioprotective and nephroprotective effects of Luteolin, a known potent antioxidant were evaluated in this study with 40 healthy rats in four experimental groups: Group A (normal saline), Groups B (30 mg/kg K2 Cr2 O7 ), Group C (Luteolin 100 mg/kg and K2 Cr2 O7 30 mg/kg), and Group D (Luteolin 200 mg/kg and K2 Cr2 O7 30 mg/kg), respectively. Markers of antioxidant defense system, oxidative stress, blood pressure and micronucleated polychromatic erythrocytes (MnPEs), immunohistochemistry of Kidney, injury molecule (Kim-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and cardiac troponin I were determined. Administration of K2 Cr2 O7 increased blood pressure parameters in systolic, diastolic and mean arterial blood pressures, markers of oxidative stress, and frequency of micronucleated polychromatic erythrocytes, together with reduction in serum nitric oxide level. Renal Kim-1 and cardiac troponin I expressions were higher, but lower expressions of renal and cardiac Nrf2 were recorded with immunohistochemical analysis. Pre-treatment with Luteolin restored blood pressure parameters, with concomitant reduction in oxidative stress indicators, augmented antioxidant mechanisms and serum Nitric oxide level, lowered the expressions of Kim-1, cardiac troponin I and up-regulated of both cardiac and renal Nrf2, reduced the frequency of micronucleated polychromatic erythrocytes. Taken together, this study therefore demonstrates the cardioprotective, nephro protective and antigenotoxic effects of Luteolin through antioxidantive and radical scavenging mechanisms.

Chemical composition, antioxidant activities and antibacterial activities of essential oil from Erythrina caffra Thunb. growing in South Africa

IntroductionEssential oils from plants are recognized as one of the most promising secondary metabolites for the development of cheap and safer drugs. While Erythrina caffra has been prominently used in folk medicine for the treatment of microbial infections, there is dearth of information on the pharmacological effectiveness and chemical composition of its essential oil. The study, therefore, aimed at identifying the chemical composition and biological activities of the essential oil of Erythrina caffra. MethodsIn this study, the essential oil was extracted with all-glass Clevenger. The antioxidant activities of the essential oil and antibacterial susceptibility assay by agar well diffusion techniques were assessed while GC-MS analysis was performed to identify the chemical constituents of the essential oil. ResultsThe study showed that the radical scavenging activity of the essential oil increases as the concentration of the essential oil increases. All bacterial isolates were susceptible to essential oil with the exception of Salmonella typhimurium and Pseudomonas aeruginosa producing inhibition zones ranging between 22 ± 1.3 and 35 ± 2.1 mm in the susceptible isolates. The GC-MS chromatogram indicated there are 35 bioactive compounds in the essential oil and Caryophyllene oxide (53.54%), [1S-(1α,7α,8aβ)]-1,2,3,5,6,7,8,8a-octa-1 - hydro-1,8a-dimethyl-7-(1-methylethenyl)-Naphthalene (7.81%), Kauran-18-al (6.49%), 10,10-Dimethyl-2,6-dimethylenebicy clo[7.2.0]undecan-5.beta.-ol (5.83%), 10s,11s-Himachala-3(12),4-diene (4.51%), Caryophyllene (3.65%) and 1- Hexanol (3.31%) were the most prominent compounds. ConclusionExcessive production of free radicals or reactive oxygen species (ROS) causes oxidative stress and disease. Oxidative stress resulting from imbalance between excessive generation of free radicals and inadequate antioxidant defense system has been linked to pathogenesis of many diseases. The essential oil of E. caffra stem bark extract possess antimicrobial and good antioxidant activities and its rich level of phytochemicals can be used as either dietary or complementary agents.

A novel combined bioactivity / chemoactivity holistic approach for the evaluation of dietary supplements

There is increasing evidence that the excessive generation of free radicals in the human body plays a major role in the pathophysiology and development of various diseases, closely associated with oxidative damage. In this frame, the consumption of antioxidant nutrients through food or dietary supplements may prevent from the harmful effects of free radicals on human cells. This work proposes a holistic approach consisting of distinct methodologies, suitable to evaluate the antioxidant and chemoprotective activity of three novel dietary supplements, each one containing active substances with complementary properties. In the first step, this approach includes in vitro studies to evaluate the antioxidant activity of the dietary supplements by measuring the parameters of free radical scavenging capacity, of reducing power activity, as well as, their ability to protect biomolecules from oxidation. Furthermore, the evaluation of their antimutagenic and antigenotoxic effects is also presented. SubsequentlySub, the specific effects of the dietary supplements were examined in three cancer cell lines (HepG2, HeLa, MKN45), by measuring redox biomarkers such as glutathione, reactive oxygen species and thiobarbituric acid reactive substances, using flow cytometry and spectrophotometry. Our results indicate that all the dietary supplements exhibit high antioxidant, antimutagenic, antigenotoxic and lipid protective activity. The most prominent result is their capability to induce oxidative damage on cancer cells via the critical decrease of the levels of their intracellular glutathione, as well as the increase of ROS and lipid peroxidation levels after the administration of non-cytotoxic concentrations. We suggest that the proposed methodology could constitute a valuable tool for the characterization of dietary supplements based on their chemical and functional properties.

Evaluation of the in vitro and in vivo antioxidant potentials of food grade Phycocyanin.

Excessive generation of oxygen free radicals plays a pivotal role in destruction of biological molecules like DNA, proteins, lipids, carbohydrates and results in various pathologies including neuronal disorders. Antioxidant molecules from natural products are reported to have ability to mitigate their production or at least halt their progression and metastasis in the system. Different studies have been performed to spot antioxidants from natural sources and attempts have been made to integrate them in conventional therapy. In our present study, food grade Phycocyanin, a nutraceutical isolated from Spirulina platensis, has been evaluated for its in vitro and in vivo antioxidant potential using a battery of antioxidant assays viz. DPPH, TAC, FRAP, hydroxyl radical, hydrogen peroxide scavenging, SOD, GSH, and LPO assays. Reducing properties of Phycocyanin were also assessed by FRAC assay. For in vivo evaluation of antioxidant profile, animal model of intracerebroventricular administration of streptozotocin was employed. Levels of oxidative stress biomarkers were measured in cortex and hippocampal parts of brain. Results obtained depicted that Phycocyanin demonstrated a dose-dependent pattern in its efficacy, which indicates the presence of free radical scavenger moieties and possible role as a neuroprotective agent.