Endogenous Antioxidant Defense Research Articles

EFFECT OF PARTHENIUM HYSTEROPHORUS ON OXIDATIVE STRESS IN PANCREATIC TISSUE OF DIABETIC RATS

Increased oxidative stress and decreased endogenous antioxidant defense has been shown to be a prominent and early features in diabetes mellitus. The present study focused on investigating the possible protective role of Parthenium hysterophorus against free radical mediated damage in pancreatic tissue of alloxan induced diabetic rats. Diabetes was induced in rats by injecting 150 mg/kg Alloxan monohydrate IP. The results revealed that administration of 50 mg/kg & 100 mg/kg of Parthenium hysterophorus extract significantly increased pancreatic glutathione, superoxide dismutase, catalase level (p<0.01) as well as significantly reduced pancreatic total nitrate/nitrite content and lipid peroxidation (p<0.01) after 72 hr. In conclusion, the study suggests that Parthenium hysterophorus is effective in significantly reducing the oxidative stress in pancreatic tissue of diabetes rats as evidenced by the increase in antioxidant enzymes, reduction of lipid peroxidation and total nitrate/nitrite level.

Adenosine monophosphate-activated protein kinase modulation by berberine attenuates mitochondrial deficits and redox imbalance in experimental diabetic neuropathy

Adenosine monophosphate-activated protein kinase (AMPK) has been studied for its myriad metabolic and mitochondrial benefits in several chronic diseases. Recent studies have uncovered its therapeutic potential against mitochondrial dysfunction in cultured dorsal root ganglion (DRG) neurons isolated from streptozotocin (STZ) induced diabetic rats. The present study is aimed at evaluating the pharmacological efficacy of berberine (BRB), a natural AMPK activator against experimental diabetic neuropathy (DN) phenotype developed in STZ (55 mg/kg, i.p.) induced diabetic rats and neurotoxicity in high-glucose (30 mM) stimulated neuro 2a (N2A) cells. Diabetic-rats have shown reduced expression of p-AMPK (Thr 172) in sciatic nerves with a consequent reduction in mitochondrial biogenesis and autophagy. BRB (50 & 100 mg/kg, po) administration to diabetic rats for 2-weeks rescued mitochondrial functional deficits and autophagy impairment by increasing the p-AMPK expression. BRB administration also augmented the NEF-2 related factor 2 (Nrf2) mediated endogenous antioxidant defence systems to restrain neuronal damage and neuroinflammation. These effects after BRB administration resulted in enhanced conduction velocity, improved nerve blood flow and attenuated hyperalgesia. Similarly, BRB exposure (5 & 10 μM) to N2A cells attenuated high glucose induced ROS generation, mitochondrial membrane depolarization through the promotion of Nrf2 mediated antioxidant defence systems. BRB exposure augmented peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) mediated mitochondrial biogenesis in neuronal cells. Results from this study signify the importance of mitoprotection conferred by BRB in DN and can be used as a preliminary basis for further molecular exploration.

Oxidative Stress As an Indicator of Metabolic Impairments in the Pathogenesis of Cerebral Stroke

Objective. To verify oxidative stress as an indicator of metabolic impairments in the complex cascade of the pathogenesis of hemorrhagic (HS) and ischemic (IS) stroke. Materials and methods. A total of 50 patients with HS and 50 with IS, along with 20 healthy subjects, were studied. All patients underwent complex biochemical blood tests, assessment of free radical oxidation (ketodienes, diene conjugates, malondialdehyde, dityrosine, and Schiff bases), and evaluation of the endogenous antioxidant defense system (vitamin E, reduced glutathione, total antioxidant activity, superoxide dismutase, glutathione peroxidase, glutathione reductase, catalase) – a total of 12 indicators. Results. In patients with IS and HS, in contrast to the control group, complex biochemical investigations revealed an increase in the intensity of free radical oxidation of lipids and proteins, along with a functional imbalance in the nonenzymatic and enzymatic branches of the endogenous antioxidant defense systems. Conclusions. These results identify two factors in the formation of oxidative stress in IS and HS, widening our knowledge of the pathogenesis of this severe vascular process.

Diffuse Axonal Injury and Oxidative Stress: A Comprehensive Review.

Traumatic brain injury (TBI) is one of the world’s leading causes of morbidity and mortality among young individuals. TBI applies powerful rotational and translational forces to the brain parenchyma, which results in a traumatic diffuse axonal injury (DAI) responsible for brain swelling and neuronal death. Following TBI, axonal degeneration has been identified as a progressive process that starts with disrupted axonal transport causing axonal swelling, followed by secondary axonal disconnection and Wallerian degeneration. These modifications in the axonal cytoskeleton interrupt the axoplasmic transport mechanisms, causing the gradual gathering of transport products so as to generate axonal swellings and modifications in neuronal homeostasis. Oxidative stress with consequent impairment of endogenous antioxidant defense mechanisms plays a significant role in the secondary events leading to neuronal death. Studies support the role of an altered axonal calcium homeostasis as a mechanism in the secondary damage of axon, and suggest that calcium channel blocker can alleviate the secondary damage, as well as other mechanisms implied in the secondary injury, and could be targeted as a candidate for therapeutic approaches. Reactive oxygen species (ROS)-mediated axonal degeneration is mainly caused by extracellular Ca2+. Increases in the defense mechanisms through the use of exogenous antioxidants may be neuroprotective, particularly if they are given within the neuroprotective time window. A promising potential therapeutic target for DAI is to directly address mitochondria-related injury or to modulate energetic axonal energy failure.

Potential protective effects of Quercetin on metalaxyl-induced oxidative stress, impaired liver functions and hepatotoxicity in rat

The purpose of this study was to investigate the protective and anti-inflammatory influence ofquercetin against metalaxyl fungicide induced liver toxicity and oxidative stress in rats. Forty twomale albino rats were divided into three equal groups. Group I (normal group): rats administereddistilled water. Group II (metalaxyl exposed group): rats received metalaxyl 1/10 LD50 (130 mg/kgb.wt) orally three times per weeks for 8 weeks. Group III (metalaxyl + quercetin treated group): ratsreceived metalaxyl (130 mg/kg b.wt) and treated with quercetin (15 mg/kg b.wt/day/i.p). Theobtained results showed significant increase in serum liver marker enzymes (ALT, AST and ALP)activities, liver tissue L-MDA and inflammatory markers (MPO and IL-6) levels in metalaxylexposed rats. However, activities of liver tissue antioxidant enzymes (SOD, CAT) and GSH levelswere markedly decreased. Administration of quercetin with metalaxyl exposed rats causedsignificant improvement of all previous parameters towards its normal ranges. These resultssuggested that, quercetin treatment may have a protective effect against metalaxyl fungicideinduced liver damage and oxidative stress in rats via anti-inflammatory activity and free radicalscavenging as well as regenerating endogenous antioxidant defense system mechanisms.

Retinoic acid receptors α and γ are involved in antioxidative protection in renal tubular epithelial cells injury induced by hypoxia/reoxygenation

Renal interstitial fibrosis (RIF) is a common outcome in various chronic kidney diseases. Injury to renal tubular epithelial cell (RTEC) is major link in RIF. Hypoxia is one of the common factors for RTEC damage. Retinoic acid receptors (RARs), RARα, RARβ and RARγ, are evolutionary conserved and pleiotropic proteins that have been involved in various cellular functions, including proliferation, differentiation, apoptosis, and transcription. Recently, we discovered that aberrant expression of RARs was involved in the development of RIF in rats. Here, we investigated the role of RARs in the hypoxia/reoxygenation (HR) damage model in RTEC with virus-based delivery vectors to knockdown or overexpress RARs. Relevant indicators were detected. Our results showed that HR inhibited RARα and RARγ expressions in a time-dependent manner in RTECs; however, the expression of RARβ was not changed obviously. RARα and RARγ overexpression could protect cells from oxidative stress-induced injury by inhibiting HR-induced intracellular superoxide anion (O2−) generation, cell viability and mitochondria membrane potential (MMP) decrease and transforming growth factor β1 (TGF-β1) expression and promoting endogenous antioxidant defense components, superoxide dismutase (SOD) and glutathione (GSH). Meanwhile, inhibition of RARα and RARγ expressions by small interference RNAs (siRNA) resulted in a less resistance of RTEC to HR as shown in increased O2− production and TGF-β1 expression and decreased cell viability, MMP, SOD and GSH levels. These data indicates that RARα and RARγ act as positive regulators to offset oxidative damage and profibrosis cytokine accumulation and therefore has an antioxidative effect.

Medicinal Plants as Protective Strategies Against Parkinson's Disease.

Parkinson's disease is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra pars compacta region. An important mechanism contributing to its development is oxidative stress, induced by the imbalance between the endogenous antioxidant defenses and free radicals production. Naturally occurring bioactive compounds exhibit high antioxidant capacity that may help reducing oxidative stress and even reverse the damage induced by ROS. Fruits are particularly rich in phytochemicals with antioxidant effect, and their properties against the development of neurodegenerative diseases are of great interest. This review discusses how the fruits bioactive compounds and synthetic analogs have been assessed for their ability to regulate molecular pathways involved in neuronal survival such as MAPK, Nrf2, and NF-κB, thus elucidating the possible therapeutic and neuroprotective actions of these compounds.

Effect of biomechanical stress on endogenous antioxidant networks in bovine articular cartilage

Mechanosensitve pathways in chondrocytes are essential for maintaining articular cartilage homeostasis. Traumatic loading increases cartilage oxidation and causes cell death and osteoarthritis. However, sub-lethal doses of the pro-oxidant molecule tert-Butyl hydroperoxide (tBHP) protects against loading-induced chondrocyte death. We hypothesized that compressive cyclic loading at moderate strains (<20%) causes sub-lethal cartilage oxidation that induces an adaptive increase in the endogenous antioxidant defense network. We tested this hypothesis by subjecting healthy bovine articular cartilage explants to in vitro static or cyclic (1 Hz) compressive loading at 50 kPa (15% strain, "physiologic") versus 300 kPa (40% strain, "hyper-physiologic") for 12 h per day for 2 days. We also treated unloaded explants with 100 μM tBHP for 12 h per day for 2 days to differentiate between biomechanical and chemical pro-oxidant stimulation. All loading conditions induced glutathione oxidation relative to unloaded controls, but only the 50 kPa cyclic loading condition increased total glutathione content (twofold). This increase was associated with a greater expression of glutamate-cysteine ligase, the rate-limiting step in glutathione synthesis, compared to 300 kPa cyclic loading. 50 kPa cyclic loading also increased the expression of superoxide dismutase-1 and peroxiredoxin-3. Like 50 kPa loading, tBHP treatment also increased total glutathione content. However, tBHP treatment and 50 kPa cyclic loading differed in their effect on the expression of genes regulating antioxidant defense and cartilage matrix synthesis and degradation. These findings suggest that glutathione metabolism is a mechanosensitive antioxidant defense pathway in chondrocytes and that intermittent pro-oxidant treatment alone is insufficient to account for all changes in mediators of cartilage homeostasis associated with cyclic loading. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:760-769, 2018.

The disturbed redox-balance in pulmonary fibrosis is modulated by the plant flavonoid quercetin

Idiopathic pulmonary fibrosis (IPF) is characterized by a disturbed pulmonary redox balance associated with inflammation. To restore this balance, antioxidants are often suggested as therapy for IPF but previous clinical trials with these compounds and their precursors have not been successful in the clinic. The exogenous antioxidant quercetin, which has a versatile antioxidant profile and is effective in restoring a disturbed redox balance, might be a better candidate. The aim of this study was to evaluate the protective effect of quercetin on oxidative and inflammatory markers in IPF. Here, we demonstrate that IPF patients have a significantly reduced endogenous antioxidant defense, shown by a reduced total antioxidant capacity and lowered glutathione and uric acid levels compared to healthy controls. This confirms that the redox balance is disturbed in IPF. Ex vivo incubation with quercetin in blood of both IPF patients and healthy controls reduces LPS-induced production of the pro-inflammatory cytokines IL-8 and TNFα. This anti-inflammatory effect was more pronounced in the blood of the patients. Our pro-fibrotic in vitro model, consisting of bleomycin-triggered BEAS-2B cells, shows that quercetin boosts the antioxidant response, by increasing Nrf2 activity, and decreases pro-inflammatory cytokine production in a concentration-dependent manner. Collectively, our findings implicate that IPF patients may benefit from the use of quercetin to restore the disturbed redox balance and reduce inflammation.

Modulation of Nrf2 by Olive Oil and Wine Polyphenols and Neuroprotection.

Strong adherence to a Mediterranean diet is associated with improved cognitive function and a lower prevalence of mild cognitive impairment. Olive oil and red wine are rich sources of polyphenols which are responsible in part for the beneficial effects on cognitive functioning. Polyphenols induce endogenous antioxidant defense mechanisms by modulating transcription factors such as the nuclear factor (erythroid-derived 2)-like 2 (Nrf2). This review discusses the scientific data supporting the modulating effect of olive oil and red wine polyphenols on Nrf2 expression, and the potential health benefits associated with cognitive functioning.

Mitigation of Acute Aluminum Toxicity by Sodium Selenite and N-Acetylcysteine in Adult Male Rats.

The objective of this study is to investigate the toxic effects of aluminum and the potential alleviation of selenite and N-acetylcysteine (NAC) on this toxicity. Acute aluminum toxicity was induced by intraperitoneal (i.p.) injection of AlCl3 (30mg Al3+/kg) for four consecutive days. Al3+ damaged the synthetic capability and regeneration power of liver cells and induced inflammation. It also damaged the kidney and disturbed the lipid profile enhancing the total cholesterol level and LDL-cholesterol level increasing the risks of atherosclerosis. Al3+ reduced the cellular antioxidant milieu typified by the decrease in reduced glutathione, vitamin E, and four antioxidant enzymes and induced lipid peroxidation (LPO). Selenite at 1mg Se/kg and NAC at 150mg/kg injected either simultaneously with or after Al3+ mitigated most of these damaging effects probably by the virtue of scavenging the free radicals, binding aluminum and stimulating its excretion and reducing its bioavailability, bolstering the endogenous antioxidant defense systems, stabilizing the cell membrane, and preventing LPO. The beneficial effects of selenite and NAC against aluminum toxicity were also confirmed by the light and electron histopathology study. There were no significant differences between the two regimens used (protection and therapeutic) in the current study probably due to the short time of exposure, and the abrogation of Al3+ toxicity offered by selenite was better than that provided by NAC on the histopathology level.

Glutathione peroxidases as oncotargets.

Oxidative stress is a disturbance in the equilibrium among free radicals, reactive oxygen species, and endogenous antioxidant defense mechanisms. Oxidative stress is a result of imbalance between the production of reactive oxygen and the biological system’s ability to detoxify the reactive intermediates or to repair the resulting damage. Mounting evidence has implicated oxidative stress in various physiological and pathological processes, including DNA damage, proliferation, cell adhesion, and survival of cancer cells. Glutathione peroxidases (GPxs) (EC 1.11.1.9) are an enzyme family with peroxidase activity whose main biological roles are to protect organisms from oxidative damage by reducing lipid hydroperoxides as well as free hydrogen peroxide. Currently, 8 sub-members of GPxs have been identified in humans, all capable of reducing H2O2 and soluble fatty acid hydroperoxides. A large number of publications has demonstrated that GPxs have significant roles in different stages of carcinogenesis. In this review, we will update recent progress in the study of the roles of GPxs in cancer. Better mechanistic understanding of GPxs will potentially contribute to the development and advancement of improved cancer treatment models.

O17 Identification and characterisation of phytochemicals activating endogenous cytoprotective mechanisms

Improved health span and lifespan extension in a wide phylogenetic range of species is associated with upregulation of the environmental stress response (ESR). The ESR, driven by the transcription factor Nrf2, provides endogenous antioxidant defence to maintain intracellular redox balance. Phytochemicals which stimulate the ESR thus upregulate cytoprotective mechanisms and ultimately contribute towards delaying the onset of age-related degenerative diseases. Two bioluminescent reporter cell lines were constructed to identify and characterise inducers of the ESR, specifically induction of Nrf2 target genes NQO1 and HMOX1 . The first cell line was generated using random integration of an exogenous luciferase gene under control of an NQO1 gene promoter, and allowed rapid and sensitive high throughput screening of natural chemical libraries. The second assay system employed a more targeted strategy using an adeno-associated virus (AAV) vector to mediate the site-specific integration of a luciferase reporter into the locus of the endogenous ESR gene HMOX1 , thus allowing predictive indexing of the gene’s transcription. The two cell lines were validated with potent ESR inducers sulforaphane and curcumin. A compound identified in the screening of a chemical library from the Marine Biodiscovery Centre (University of Aberdeen, UK) was further characterised in a microarray experiment and compared to known phytochemicals. In combination, these in vitro cell-based assay systems will allow a better understanding of the activity-structure relationship of ESR inducers, and assess the bioactivity of phytochemical metabolites from human serum samples following intervention trials.

Role of Antioxidants in the Management Diabetes Mellitus

Diabetes mellitus (DM), commonly referred to as diabetes, is a group of metabolic diseases in which there are high blood sugar levels over a prolonged period. Symptoms of high blood sugar include frequent urination, increased thirst and increased hunger. If left untreated, diabetes can cause many complications. Acute complications can include diabetic ketoacidosis, nonketotic hyperosmolar coma, or death. Serious long-term complications include heart disease, stroke, chronic kidney failure, foot ulcers, and damage to the eyes. Oxidative stress plays a major role in the pathogenesis and development of complications of both types of DM. However, the exact mechanism by which oxidative stress could contribute to and accelerate the development of complications in diabetic mellitus is only partly known and remains to be clarified. On the one hand, hyperglycemia induces free radicals; on the other hand, it impairs the endogenous antioxidant defense system in patients with diabetes. Endogenous antioxidant defense mechanisms include both enzymatic and non-enzymatic pathways. Their functions in human cells are to counter balance toxic reactive oxygen species (ROS). Common antioxidants include the vitamins A, C, and E, glutathione (GSH), and the enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GRx). Many natural antioxidants can be used in lowering blood glucose level. This review describes the importance of natural antioxidants to be included in the diet to reduce the hyperglycemic effect.

Naringenin Ameliorates Behavioral Dysfunction and Neurological Deficits in a d-Galactose-Induced Aging Mouse Model Through Activation of PI3K/Akt/Nrf2 Pathway.

In this study, we evaluated the protective effects of naringenin on aging mice induced by d-galactose (d-gal). Open field test and Morris water maze test were performed to evaluate the effect of naringenin on behavioral dysfunction. Hematoxylin-eosin staining, TUNEL staining, and Nissl staining were used to estimate the effect of naringenin on neurological deficits. Furthermore, naringenin markedly activated PI3K/Akt signaling, eventually promoted the nuclear translocation of nuclear factor-erythroid 2-related factor 2, and induced the expression of heme oxygenase 1 and NAD(P)H-quinone oxidoreductase 1. Superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid reactive substances (TBARS) assays were conducted to evaluate oxidative stress in d-gal-induced aging mice. Our finding demonstrated that naringenin was a promising agent for attenuating the aging process, and enhancing endogenous antioxidant defense capacity was a reliable strategy to delay the senescence process.

Genipin attenuates cisplatin-induced nephrotoxicity by counteracting oxidative stress, inflammation, and apoptosis

Cisplatin (CP) is a potent and widely used chemotherapeutic agent. However, the clinical benefits of CP are compromised because it elicits nephrotoxicity and ototoxicity. In this study, we investigated the nephroprotective effects of the phytochemical genipin (GP) isolated from the gardenia (Gardenia jasminoides) fruit, using a murine model of CP-induced nephropathy. GP pretreatment attenuated the CP-induced renal tissue injury by diminishing the serum blood urea nitrogen, creatinine, and cystatin C levels, as well as those of kidney injury molecule-1. In addition, GP attenuated the CP-induced oxidative/nitrative stress by suppressing the activation of NADPH oxidase, augmenting the endogenous antioxidant defense system, and diminishing the accumulation of 4-hydroxynonenal and 3-nitrotyrosine in renal tissues. Furthermore, reduced levels of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 beta indicated that CP-induced renal inflammation was mitigated upon the treatment with GP. GP also attenuated the CP-induced activation of mitogen-activated protein kinases, excessive activities of caspase-3/7 and poly(ADP-ribose) polymerase, DNA fragmentation, and apoptosis. When administered 12h after the onset of kidney injury, GP showed a therapeutic effect by ameliorating CP-induced nephrotoxicity. Moreover, GP synergistically enhanced the CP-induced cell death of T24 human bladder cancer cells. Collectively, our data indicate that GP attenuated the CP-induced renal tissue injury by abrogating oxidative/nitrative stress and inflammation and by blocking cell death pathways, thereby improving the renal function. Thus, our results suggest that the use of GP may be a promising new protective strategy against cisplatin-induced nephrotoxicity.

Anti-obesity effects of yellow catfish protein hydrolysate on mice fed a 45% kcal high-fat diet.

Obesity contributes to the etiologies of a variety of comorbid conditions, such as type 2 diabetes, hypertension and cardiovascular disease. In the present study, the anti-obesity effects of yellow catfish protein hydrolysate (YPh) were observed in mice fed a 45% kcal high-fat diet (HFD) compared with those of mice treated with simvastatin. The HFD-fed control mice exhibited noticeable increase in body weight, and whole-body and abdominal fat densities, periovarian and abdominal wall-deposited fat pad weight, as well as in the levels of triglycerides (TG), blood total cholesterol (TC), low-density lipoprotein, alanine aminotransferase, aspartate aminotransferase, creatinine, blood urea nitrogen, and in the fecal TG and TC contents. However, they exhibited a decrease in serum high-density lipoprotein levels. In addition, an increase was detected in periovarian and dorsal abdominally deposited fat pad thickness, adipocyte hypertrophy, the number of steatohepatitis regions, hepatocyte hypertrophy and lipid droplet deposition-related renal tubular vacuolation degenerative lesions, along with increased hepatic lipid peroxidation and a deteriorated endogenous antioxidant defense system (glutathione, catalase and superoxide dismutase). However, all the above-mentioned obesity-related complications were dose-dependently and significantly inhibited after 84 days of thye consecutive oral administration of 125, 250 and 500 mg/kg YPh. In addition, YPh dose-dependently depleted the liver endogenous antioxidant defense system and inhibited hepatic lipid peroxidation. Overall, the effects of 250 mg/kg YPh on HFD-induced obesity and related complications were similar or more potent than those of 10 mg/kg simvastatin. These results indicate that YPh is a promising new potent medicinal ingredient for possible use in the treatment of obesity and related complications.

Role of Oxidative Stress in Renal Transplantation: Bases for an n-3 PUFA Strategy Against Delayed Graft Function

Renal transplantation (RT) is considered the "gold standard" treatment for end-stage renal disease patients. Efforts should be made to reduce ischaemia-reperfusion (IR) injury, which unavoidably occurs in RT as long as several clinical settings, i.e. open-heart surgeries, prosthesis implantation, among others. It is well known that IR is primarily responsible for injury associated with RT. Consequently, tissue inflammation and organ dysfunction will ensue due to the occurrence of oxidative stress (OS) in the reperfused tissue, a condition generated when endogenous antioxidant defences become overwhelmed by a massive production of reactive oxygen species. Furthermore, OS is involved in the impairment of renal function, leading to deleterious conditions such as delayed graft function (DGF), which is a common clinical expression of IR injury in RT. Omega-3 polyunsaturated fatty acids (n -3 PUFA) have been widely used in different clinical settings to counteract the deleterious effects of OS. Thus, based on the currently available literature, the central aim of this review was to propose an n-3 PUFAbased strategy targeting the key role of OS in the pathophysiology of renal IR injury in order to encourage protection against the occurrence of DGF.

Antioxidant Activity of Yichun Blue Honeysuckle (YBHS) Berry Counteracts CCl₄-Induced Toxicity in Liver Injury Model of Mice.

Yichun Blue Honeysuckle (YBHS) is reported to have a broad range of health benefits including protection against a number of chronic diseases. The objective of our study was to determine whether YBHS exhibits antioxidant activity, and if so, determine how it provides protection against oxidative stress. Eight-week old mice (25 male and 25 female) were randomized into five groups (n = 10 per group). YBHS extract (at 6.25%, 12.5%, or 25%) was administrated via intra-gastric tube to mice at 0.1 mL/10 g body weight once daily for 7 days. On the 8th day, all animals except for the controls received 250 mg/kg of CCl4 through an intra-gastric tube. The animals were sacrificed 6 h after CCl4 administration. Liver samples obtained from these mice were analyzed for the levels of Thiobarbituric Acid Reactive Substances (TBARS) and glutathione and the activities of Superoxide Dismutase (SOD), Catalase (CAT), and Glutathione Peroxidase (GPx), using biochemical assay kits. Our results showed that YBHS indeed reduces lipid peroxidation, suggesting that YBHS decreases the Reactive Oxygen Species (ROS) levels. We also found that YBHS activated the endogenous antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase and its co-enzyme glutathione reductase. In addition, we showed that glutathione levels were increased by YBHS treatment. Furthermore, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay revealed that YBHS has potent free radical scavenging activity. Based on the results from our study, we conclude that YBHS scavenges ROS by enhancing the activity of the endogenous antioxidant defense system activity for conferring liver protective effects.

Melatonin Reduces Oxidative Stress Damage Induced by Hydrogen Peroxide in Saccharomyces cerevisiae

Melatonin (N-acetyl-5-methoxytryptamine), which is synthesized from tryptophan, is formed during alcoholic fermentation, though its role in yeast is unknown. This study employed Saccharomyces cerevisiae as an eukaryote model to evaluate the possible effects of melatonin supplementation on endogenous cellular defense systems by measuring its effects on various cellular targets. Cell viability, intracellular reduced and oxidized glutathione levels (GSH and GSSG, respectively), reactive oxygen species (ROS) production, and expression of genes related to antioxidant defense in yeast, such as the glutathione system, catalase, superoxide dismutase, glutaredoxin, and thioredoxin, were assessed. Melatonin alone decreased GSH, increased GSSG, and activated antioxidant defense system genes, which reached maximum levels in the stationary phase. These results indicate that melatonin supplementation enables cells to resist better the stress generated in the stationary phase. However, when cells were subjected to oxidative stress induced by H2O2, melatonin was able to partially mitigate cell damage by decreasing ROS accumulation and GSH and increasing GSSG; this was followed by enhanced cell viability after stress exposure, mostly when occurring in the early stationary phase. Additionally, under such conditions, most genes related to endogenous antioxidant defense continued to be up-regulated with melatonin supplementation. The findings demonstrate that melatonin can act as antioxidant in S. cerevisiae.