Cellular Antioxidant Status Research Articles

Exogenous Reactive Oxygen Species Augments SMAD4 Expression And TGF-β Paradox in Human Breast Cancer

Background: The Transforming growth factor-β (TGF-β) functions to induce apoptosis, cell cycle arrest, and differentiation is central to sustaining tissue homeostasis and maintaining genomic stability. TGF-β normally, an effective tumor-suppressor that restricts the uncontrolled division of cells augments the development and progression of human malignancies when cytostatic activities of TGF-β are resisted by genetic and epigenetic events caused by tumorigenesis. This dichotomic nature of TGF-β during oncogenesis termed as “TGF-β Paradox,” persists to be the most crucial and puzzling query regarding its physio-pathological function and the role of cellular antioxidant status is highly interrelated which warrants more studies on the role of endogenous reactive oxygen species (ROS) in deciding epithelial-mesenchymal transition (EMT) process. The objective of the study was to check whether enhanced ROS augments the TGF-β pathway facilitating EMT. Methods: In vitro toxicity assay was performed to assess the appropriate concentration of hydrogen peroxide (H2O2) imparting oxidative stress. Comet assay and 8-OHdG (8-hydroxy-2’-deoxyguanosine) enzyme-linked immunosorbent assay (ELISA) were performed to check the extent of DNA damage and adduct production respectively. Mitogen-activated protein kinase (MAPK) p38 ELISA and mRNA gene expression analysis of TGF-β and SMAD were done to verify the effect of H2O2 on these signaling. Results: The objective of the study was to check whether enhanced ROS augments the TGF-β pathway facilitating EMT. Along with morphological alterations, a dose-dependent decrease in cell viability was seen at 300µM of H2O2 compared to 75µM. DCFDA labeling discovered the dose-dependent gradation of intracellular ROS generation and this was correlated to increased cellular DNA damage and DNA adduct production which was increased linearly with increasing H2O2 as evident with comet test and 8-OHdG ELISA. Significantly reduced MAPK p38 activity revealed by indirect ELISA analysis suggests lessened suppression of cell growth. Conclusions: The study establishes that higher intracellular ROS will facilitate the TGF-β paradox leading to epithelial mesenchymal transition which can adversely affect therapeutic strategies targeting EMT

Impacts of ocean acidification and hypoxia on cellular immunity, oxygen consumption and antioxidant status in Mediterranean mussel

There is growing recognition that the hypoxic regions of the ocean are also becoming more acidic due to increasing levels of global carbon dioxide emissions. The impact of water acidification on marine life is largely unknown, as most previous studies have not taken into account the effects of hypoxia, which may affect how organisms respond to low pH levels. In this study, we experimentally examined the consequences of water acidification in combination with normoxic or hypoxic conditions on cellular immune parameters in Mediterranean mussels. We measured total hemocyte counts in hemolymph, the cellular composition of hemolymph, phagocytosis, reactive oxygen species (ROS) production. General response of the organism was evaluated on the basis of the activity of antioxidant enzymes in the hepatopancreas, as well as respiratory rates over an 8-day exposure period. The mussels were exposed to low pH conditions (7.3), either under normoxic conditions (dissolved oxygen concentration of 8 mg/L) or hypoxic conditions (dissolved oxygen concentration of 2 mg/L). The parameters were assessed at days 1, 3, 6, and 8 of the experiment. Experimental acidification under normoxic conditions reduced THC and ROS production by hemocytes during later stages of exposure, but phagocytic activity (PA) only decreased at day 3 and then recovered. Combined acidification and hypoxia suppressed PA in hemocytes at the beginning of exposure, while hemocyte ROS production and THC decreased by the end of the experiment. The hemolymph cellular composition and activity of antioxidant enzymes were unaffected by acidified conditions under different oxygen regimes, but mussel respiratory rate (RR) decreased with a more significant reduction in oxygen consumption under hypoxia. Mussels showed a relatively high tolerance to acidification in combination with various dissolved oxygen levels, although prolonged acidification exposure led to increased detrimental effects on immunity and metabolism.

Supercritical CO2 Extraction of Terpenoids from Indocalamus latifolius Leaves: Optimization, Purification, and Antioxidant Activity.

This study aimed to investigate the efficacy of supercritical CO2 (SC-CO2) extraction in enhancing the extraction rate, purity, and antioxidant activity of Indocalamus latifolius (Keng) McClure (Poaceae) leaf terpenoids (ILLTs). Crude extracts obtained from leaves were subjected to qualitative and quantitative analyses, revealing neophytadiene, phytol, β-sitosterol, β-amyrone, squalene, and friedelin as the primary terpenoid constituents, identified through gas chromatography-mass spectrometry (GC-MS). Compared with steam distillation extraction (SD), simultaneous distillation extraction (SDE), ultra-high pressure-assisted n-hexane extraction (UHPE-Hex), ultra-high pressure-assisted ethanol extraction (UHPE-EtOH), ultrasound-assisted n-hexane extraction (UE-Hex), and ultrasound-assisted ethanol extraction (UE-EtOH), SC-CO2 exhibited a superior ILLT extraction rate, purity, and antioxidant activity. Scanning electron microscopy (SEM) observations of the residues further revealed more severe damage to both the residues and their cell walls after SC-CO2 extraction. Under optimal parameters (4.5 h, 26 MPa, 39 °C, and 20% ethyl alcohol), the ILLT extraction rate with SC-CO2 reached 1.44 ± 0.12 mg/g, which was significantly higher than the rates obtained by the other six methods. The subsequent separation and purification using WelFlash C18-l, BUCHI-C18, and Sephadex LH-20 led to an increase in the purity of the six terpenoid components from 12.91% to 93.34%. Furthermore, the ILLTs demonstrated cytotoxicity against HepG2 cells with an IC50 value of 148.93 ± 9.93 μg/mL. Additionally, with increasing concentrations, the ILLTs exhibited an enhanced cellular antioxidant status, as evidenced by reductions in both reactive oxygen species (ROS) and malondialdehyde (MDA) levels.

Alkaloid-rich extract of Buchholzia coriacea seed mitigate the effect of copper-induced toxicity in Drosophila melanogaster

AbstractBuchholzia coriacea is known for its anti-oxidative, anti-inflammatory, and anti-diabetic properties. This study evaluated the effect of alkaloid-rich extract of Buchholzia coriacea seed (ArEBCs) against copper-induced toxicity in Drosophila melanogaster. The flies were exposed to graded doses (25 to 200 mg/kg diet) of ArEBCs for 12 days and thereafter, a survival test was carried out to determine the safe and therapeutic doses used in the ameliorative study. For this, flies were exposed to CuSO4 (1 mM) alone or in combination with ArEBCs (25 and 50 mg/kg diet) for 5 days. Locomotor activity and biochemical assays such as glucose (GLU) level, acetylcholinesterase (AChE) activity, malonaldehyde (MDA) and antioxidant biomarkers (catalase and reduced glutathione) were performed to assess the effect of ArEBCs on the copper-induced flies. Copper-exposed flies showed reduced survival rates and disrupted locomotor activity when compared to the control flies. In addition, a significant (p < 0.05) increase in AChE activity, GLU and MDA levels and a decrease in the antioxidant biomarkers activities were observed in the copper-exposed flies. Treatment of flies with ArEBCs mitigated the negative effect of copper on the flies by increasing the survival rate of the flies, reducing the activities of AChE, GLU and MDA. The activities of the cellular antioxidant status were also significantly (p < 0.05) increased. This study suggests that ArEBCs could mitigate the effect of copper-induced oxidative damage in Drosophila melanogaster and could be considered a potential therapeutic agent against copper-induced oxidative damage.

Chia seeds and coenzyme Q10 alleviate iron overload induced hepatorenal toxicity in mice via iron chelation and oxidative stress modulation

Iron overload (IOL) can cause hepatorenal damage due to iron-mediated oxidative and mitochondrial damage. Remarkably, combining a natural iron chelator with an antioxidant can exert greater efficacy than monotherapy. Thus, the present study aimed to evaluate the efficacy of Chia and CoQ10 to chelate excess iron and prevent hepatorenal oxidative damage in IOL mice. Male Swiss albino mice (n = 49) were randomly assigned to seven groups: control, dietary Chia, CoQ10, IOL, IOL + Chia, IOL + CoQ10, and IOL + Chia + CoQ10. Computational chemistry indicates that the phytic acid found in the Chia seeds is stable, reactive, and able to bind to up to three iron ions (both Fe2+ and Fe3+). IOL induced a significant (P < 0.05) increase in serum iron, ferritin, transferrin, TIBC, TSI, RBCs, Hb, MCV, MCH, WBCs, AST, ALT, creatinine, and MDA. IOL causes a significant (P < 0.05) decrease in UIBC, platelets, and antioxidant molecules (GSH, SOD, CAT, and GR). Also, IOL elicits mitochondrial membrane change depolarization, and DNA fragmentation and suppresses mitochondrial DNA copies. Furthermore, substantial changes in hepatic and renal tissue, including hepatocellular necrosis and apoptosis, glomerular degeneration, glomerular basement membrane thickening, and tubular degeneration, were observed in the IOL group. Dietary Chia and CoQ10 induced significant (P < 0.05) amelioration in all the mentioned parameters. They can mostly repair the abnormal architecture of hepatic and renal tissues induced by IOL, as signified by normal sinusoids, normal central veins, and neither glomerular damage nor degenerated tubules. In conclusion, the combined treatment with Chia + CoQ10 exerts more pronounced efficacy than monotherapy in hepatorenal protection via chelating excess iron and improved cellular antioxidant status and hepatorenal mitochondrial function in IOL mice.

A Mini Review on Pancreatin: Prodigious Focus on Hepatic Ischemia-Reperfusion Injury

Pancreatin is a natural mixture of digestive enzymes derived from the pancreas of vertebrates. Recent studies have demonstrated that pancreatin has protective effects against various types of hepatic ischemia-reperfusion (I/R) injury. In this review, we summarize the existing evidence regarding the protective effects of pancreatin on hepatic I/R injury. We discuss the potential mechanisms behind the protective effects of pancreatin, including its anti-inflammatory, antioxidative, anti-apoptotic, and anti-fibrotic effects. Moreover, we discuss the potential application of pancreatin as a therapeutic agent in the treatment of I/R injury in the liver. Numerous studies have shown that pancreatin can protect against hepatic ischemia-reperfusion (I/R) injury by targeting multiple pathways and processes involved in I/R injury, including reduction in oxidative stress, suppressing inflammatory response, promoting cell proliferation as well as improvement in apoptosis process. In addition, pancreatin has a protective effect on liver injury by promoting the antioxidant defence system, inhibiting the accumulation of intracellular lipid peroxides, and restoring cellular antioxidant status. Thus, pancreatin may be a promising and effective treatment for hepatic I/R injury, and further research is needed to explore its clinical efficacy. In conclusion, pancreatin is a potential natural remedy that has been studied to potentially reduce hepatic I/R injury. Although further research is needed to confirm the efficacy of pancreatin in clinical settings, it has been suggested that it can act as a natural remedy for hepatic I/R injury due to its multiple mechanisms of action and its ability to restore the balance of oxidative stress. Pancreatin has been studied as a potential natural remedy for hepatic I/R injury due to its ability to inhibit lipid peroxidation, promote antioxidant defence system activity, and restore cellular antioxidant status. Keywords: Pancreatin, hepatic ischemia-reperfusion, antioxidant activity, PI3K-AKT pathway, hepatoprotective strategies.

The effect of functional bars on the biochemical parameters of blood during physical exertion

Currently, the fast pace of life, changes in consumers’ habits, and the trend toward a healthy lifestyle around the world create the need for new healthy foods for immediate consumption. In this regard, the production of snacks with high nutritional value, as well as giving them functional properties through the use of various types of raw materials, seems promising. The choice of components following the physiological needs of various population groups in snack production allows getting new specialized food products, which improves people's quality of life and health. The most promising is the production of functional snack bars by combining vegetable and dairy raw materials. It is promising to use mare’s milk as a dairy raw material. The clinical efficacy of the new fruit-protein bars based on mare’s milk (FBBs) was tested on 25 volunteers aged 25-35 years for 60 days. The control group consisted of 15 people who received two KDV fruit and nut bars for 60 days, the nutritional and energy value of which was comparable to the snacks studied. Before and after taking snacks, blood biochemical and immunological parameters were evaluated. The results indicate a positive effect of new snacks based on mare’s milk on performance indicators, the state of cellular immunity, blood parameters, biochemical parameters, and antioxidant status. There is a decrease in fat mass, intracellular and extracellular fluid levels, and a reducing the number of final and intermediate lipid peroxidation products. The blood level of haemoglobin, erythrocytes, platelets, hematocrit, and all classes of immunoglobulins increased. Specialized functional protein bars, enriched with dry mare’s milk, can be recommended to various categories of the population experiencing intensive physical activity and psychoemotional stress to increase their adaptive capabilities and performance.

Effects of Alternanthera sessilis Red leaf extracts on hydrogen peroxide-induced oxidative stress in HepG2 cells and identification of phytochemicals using HPLC-QToF-MS/MS

Alternanthera sessilis Red (ASR) is an edible medicinal plant that receives little attention in Asia. This study aimed to investigate the ability of ASR ethanolic (EtOH ASR ) and ethyl acetate (EtAC ASR ) leaf extracts in protecting HepG2 cells against oxidative damage. To determine the effect of both extracts on the cellular antioxidant status and preventive activities against hydrogen peroxide (H 2 O 2 )-induced oxidative stress, HepG2 cells were treated with both extracts at concentration ≤ 20 µg/mL as the extracts were shown low toxicity. With increasing concentrations, both extracts improved cellular antioxidant status where cells treated with EtAC ASR showed a higher ferric reducing activity than the EtOH ASR . Both extracts also reduced the levels of reactive oxygen species and inhibited lipid peroxidation in the cells. The highest cytoprotective activity against H 2 O 2 -induced cell damage was exhibited by EtAC ASR at 5 µg/mL. HPLC-QToF-MS/MS analysis tentatively identified the presence of 30 phytochemicals in both extracts with 28 of them comprising of polyphenols, whereas two carotenoids were found only in the EtOH ASR . These may be responsible for the cytoprotective properties of the ASR leaf. The current findings highlight the potential of ASR leaf as a source of natural antioxidants for protecting cells from oxidative damage. Furthermore, newly discovered phytochemical compounds in ASR, particularly polyphenols, which are mostly flavonoids, could be useful for future research into its potential as a functional food or nutraceutical against oxidative stress-related diseases. • EtOH ASR and EtAC ASR significantly protected HepG2 cells against oxidative stress. • EtAC ASR inhibited intracellular ROS more effectively at 5 µg/mL. • EtAC ASR was also better in reducing lipid peroxidation induced by H 2 O 2 at 5 µg/mL. • Two carotenoids and 28 polyphenols were tentatively identified in the extracts.

Ficus exasperata Attenuates Acetaminophen-Induced Hepatic Damage via NF-κB Signaling Mechanism in Experimental Rat Model.

Ficus exasperata has been used to treat ulcer, diabetes, fever, and a variety of stress-related disorders. Acetaminophen (APAP) overdose is the most common cause of drug-induced acute liver injury. In this study, we evaluated the hepatoprotective effect and antioxidant capacity of ethanolic extract of F. exasperata (EFE) on acetaminophen-induced hepatotoxicity in albino rats. Rats were pretreated with EFE (150, 250, 500 mg/kg) and thereafter received 250 mg/kg APA intraperitoneally (i.p.). The normal control group received distilled water, while the negative control group received 250 mg/kg APAP, respectively. Hepatotoxicity and oxidative stress-antioxidant parameters were then assessed. Flavonoids, saponins, steroids, and glycosides, but not phenolics were detected by EFE phytochemical analysis. No mortality was recorded on acute exposure of rats to varying concentrations of APAP after 24 h; however, a dose-dependent increase in severity of convulsion, urination, and hyperactivity was observed. APAP overdose induced high AST, ALT, ALP, and total bilirubin levels in the serum, invoked lipid peroxidation, depleted GSH, decreased CAT, SOD, and GST levels, respectively. Nitric oxide (NO) level, myeloperoxidase activity, TNF-α, IL-1β, NF-κB, COX-2, MCP-1, and IL-6 were also increased. Importantly, pretreatment of rats with EFE before acetaminophen ameliorated and restored cellular antioxidant status to levels comparable to the control group. Our results show and suggest the hepatoprotective effect of F. exasperata and its ability to modulate cellular antioxidant status supports its use in traditional medicine and renders it safe in treating an oxidative stress-induced hepatic injury.

Jobelyn® extends the life span and improves motor function in Drosophila melanogaster exposed to lipopolysaccharide via augmentation of antioxidant status.

Jobelyn® (JB), a dietary supplement, derived from polyphenol-rich leaf sheath of Sorghum bicolor, has been reported to attenuate sensorimotor deficits and oxidative stress evoked by complete Freund-adjuvant in mice. This present study evaluated its effects on the life span, motor function and changes in oxidative stress parameters as well as acetylcholinesterase activity in Drosophila melanogaster exposed to lipopolysaccharide (LPS). The flies (50 per vial), in 5 replicates were fed with LPS (250μg/kg diet) alone or in combination with JB (0.25-1.0mg/kg diet) daily for 7days. The mortality rate and motor function were evaluated on day 7. The flies were afterwards processed for determination of oxidative stress parameters and acetylcholinesterase activity. The effects of JB (0.25-1.0mg/g diet) on the longevity of Drosophila was also investigated wherein the flies were monitored daily for mortality throughout their lifespan. The flies exposed to LPS (250μg/kg diet) had reduced life span and elevated oxidative stress when compared with control. However, JB (0.25 and 1.0mg/kg diet) improved the motor function and also reduced the mortality rate of the flies exposed to LPS. It also restored the cellular antioxidant status and reduced acetylcholinesterase activity, accumulation of hydrogen peroxide as well as nitric oxide in Drosophila fed with LPS. JB also extended the longevity of the fliesrelative to control. The findings that JB improves motor function and extended the lifespan of Drosophila flies by boosting the antioxidant status and cholinergic function, suggest it might be helpful in delaying the onset of neuropsychiatric illnesses associated with the aging processes.

Azima tetracantha Leaf Methanol Extract Inhibits Gastric Cancer Cell Proliferation through Induction of Redox Imbalance and Cytochrome C Release

Azima tetracantha is a traditionally used medicinal plant in the Ayurvedic system and folk medicines. The plant has been used for various purposes including inflammatory ailments, arthritis, and various types of toxicities. There are no available reports on its anticancer activity; hence, the study aimed to evaluate its anti-proliferative potential in gastric cancer cells (AGS and KATO III). We observed a dose-dependent decrease in cell proliferation in both the gastric cancer cells; furthermore, a concomitant reduction in the cellular antioxidant status was observed. Pre-treatment with A. tetracantha methanol extract showed a significant reduction in intracellular glutathione levels, and subsequently raised thiobarbituric acid reactive substances. Together with this, a significant increase in the cytochrome c release was noted in A. tetracantha treated cells, alongwith an increase in the expression of pro-apoptotic genes such as BAX, CASP3, CASP7 and APAF1. Furthermore, RTqPCR analysis indicated an increased expression of the anti-apoptotic gene BCL2 in a dose-dependent manner. In addition, to confirm the role of reactive oxygen species in the proliferation inhibition, DCFH-DA-based analysis was carried out, where a dose-dependent increase in ROS levels was observed in these cells. Overall, the study confirms the anticancer efficacy of A. tetracantha leaf methanol extract mediated through the induction of redox imbalance and cytochrome c release.

3,4-Dihydroxybenzaldehyde mitigates fluoride-induced cytotoxicity and oxidative damage in human RBC

BackgroundFluoride is an essential micronutrient that is needed for mineralization of bones and formation of dental enamel. It is a widely dispersed environmental pollutant and chronic exposure to it is toxic, resulting in malignancies and hematological damage in humans. Blood is a major and early target of environmental pollutants and toxicants like fluoride. Fluoride generates reactive oxygen species and free radicals which induce oxidative stress in target cells and mediate its toxic effects. The aim of this study was to determine the mitigating effect of plant antioxidant 3,4-dihydroxybenzaldehyde (DHB) on sodium fluoride (NaF) induced oxidative damage and cytotoxicity in isolated human red blood cells (RBC) MethodIsolated human RBC were treated with 0.5 mM NaF, in absence or presence of different concentrations of DHB (0.1–2.5 mM). Several biochemical parameters were analyzed in cell lysates and whole cells. ResultsTreatment of RBC with NaF increased the formation of reactive oxygen and nitrogen species. It oxidized thiols, proteins and lipids and generated their peroxidative products. Methemoglobin level, heme degradation and lipid peroxidation were increased but cellular antioxidant status declined significantly in NaF alone treated RBC, compared to the control. NaF inhibited antioxidant, membrane bound and glycolytic enzymes in RBC. However, prior incubation of RBC with DHB significantly attenuated the NaF-induced alterations in all these parameters in a DHB concentration-dependent manner. ConclusionThese results show that DHB mitigates NaF-induced oxidative damage in human RBC, probably because of its antioxidant character.

Farnesol alleviates diethyl nitrosamine induced inflammation and protects experimental rat hepatocellular carcinoma.

Hepatocellular carcinoma is a well-known internal malignancy with increased worldwide mortality. The increased progression rate is closely associated with chronic liver diseases such as cirrhosis. Chemical carcinogens cause tumor advocacy over free radical metabolites to causes numerous biochemical and molecular changes that bring oxidative stress. In addition, inflammatory cells and its growth factor promotes the progression of liver cancer through deregulates the numerous cellular signaling pathways involved in normal cellular proliferation. Plant derived phytochemicals have a better complimentary potency to defend against a wide array of free radical mediated diseases such as cancer. More recently, we have evaluated the anticancer effect of Farnesol against DEN induced hepatocellular carcinoma in male wistar albino rats. However, the possible mechanism in which Farnesol attributes its anticancer effect against DEN induced liver cancer remains unknown. Hence in the present study, an attempt has been made to reduce the oxidative stress by appraise the antioxidant effect by Farnesol in DEN induced hepatocellular carcinoma. Elevated oxidative stress markers with concomitant decreased cellular antioxidants levels were observed in DEN induced hepatic tissues. Further, proliferating nuclei with increased proliferating cell nucleolar antigen (PCNA) and inflammatory mediator expression were observed in DEN induced rats. Oral supplementation of Farnesol to DEN induced rats significantly decrease the oxidative stress markers and increase the cellular antioxidant status. Moreover, Farnesol treatment decreases the argyrophilic nuclear organizer region and PCNA along with decreased expression of inflammatory mediators suggest that Farnesol treatment restores DEN induced hepatic abnormalities and protects liver from cancer progression.

Effects of commonly used medicinal herbs in Jordan on erythrocyte oxidative stress markers

Context: Much attention has been given recently to the antioxidant capacity of natural products, with particular interest on those that are frequently consumed by people. Aims: To evaluate the commonly used and frequently consumed edible herbs in Jordan to compare their in vitro and in vivo antioxidant properties. Methods: The in vitro antioxidant properties were tested by pre-incubating washed human erythrocytes with a given herb extract and then exposing these erythrocytes to H2O2 to induce oxidative stress, and then measuring erythrocyte malondialdehyde (MDA) as a marker for lipid peroxidation, protein carbonyl (PC) as a marker for protein oxidation, reduced glutathione (GSH) as a marker for cellular antioxidant status and the percentage of hemolysis as an indicator for the anti-hemolytic activity of the herb. The in vivo antioxidant properties were tested by giving orally aqueous extracts of the herbs tested in vitro to healthy individuals on daily bases for five days, with two blood samples being collected from each individual to measure the above-mentioned markers. Results: Pre-incubation of human erythrocytes in vitro with methanolic extracts of Zingiber officinale, Rosmarinus officinalis, Salvia triloba, Verbena triphylla, Nigella sativa and Origanum syriacum significantly improved erythrocyte MDA, PC and oxidant hemolysis. Oral consumption by healthy individuals of aqueous extracts of the same herbs for 5 days significantly improved erythrocyte MDA, GSH, and superoxide dismutase (SOD) at the sixth day of administration. Conclusions: These results indicate that aqueous extracts of medicinal herbs can be absorbed well and appear in body tissues inflecting in vivo antioxidant properties similar to their in vitro properties.

Antiviral, Antibacterial, Antifungal, and Antiparasitic Properties of Propolis: A Review.

Propolis is a complex phytocompound made from resinous and balsamic material harvested by bees from flowers, branches, pollen, and tree exudates. Humans have used propolis therapeutically for centuries. The aim of this article is to provide comprehensive review of the antiviral, antibacterial, antifungal, and antiparasitic properties of propolis. The mechanisms of action of propolis are discussed. There are two distinct impacts with regards to antimicrobial and anti-parasitic properties of propolis, on the pathogens and on the host. With regards to the pathogens, propolis acts by disrupting the ability of the pathogens to invade the host cells by forming a physical barrier and inhibiting enzymes and proteins needed for invasion into the host cells. Propolis also inhibits the replication process of the pathogens. Moreover, propolis inhibits the metabolic processes of the pathogens by disrupting cellular organelles and components responsible for energy production. With regard to the host, propolis functions as an immunomodulator. It upregulates the innate immunity and modulates the inflammatory signaling pathways. Propolis also helps maintain the host’s cellular antioxidant status. More importantly, a small number of human clinical trials have demonstrated the efficacy and the safety of propolis as an adjuvant therapy for pathogenic infections.

Management of Bisphenol-A Induced Hepato-Renal Disorder in Wistar Rat by Wheatgrass Aqueous Extract Co-Administration

Bisphenol-A (or BPA) is a renowned endocrine disruptor in current use. This study concentrated on the restorative effects of wheatgrass methanolic extract (WG-ME) on the liver and kidney in rats treated with BPA. For this purpose, 18 Wistar rats were divided into 3 groups: Control; BPA (100mg/kg); BPA+ WG-ME (100 mg/kg BPA + 200mg/kg WG-ME) by oral gavage for 28 days study period. Dissected liver and kidney were procured and stored at -20oC for the evaluation of cellular antioxidant status. For the analysis of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea and creatinine levels, which have a role in measuring liver and kidney toxicity, blood samples were collected. In parallel, BPA decreases cellular antioxidant levels super-di-oxide (SOD), catalase and GPx in liver and kidney. The hepato-renal functional tests and antioxidant enzyme levels were significantly improved with the addition of WG-ME oral consumption. These findings provided that protective effect of WG-ME improving BPA-induced metabolic alterations.

Methionine alleviates aflatoxinb1-induced broiler chicks embryotoxicity through inhibition of caspase-dependent apoptosis and enhancement of cellular antioxidant status

Practical methods for preventing embryotoxicity in chickens that are caused by aflatoxin-B1 (AFB1) are currently rare. Binding absorbers are commonly used in feeding stuff to reduce laying hens' exposure to off-contaminated diets, thus reducing residue exposure to fertilized eggs. Nonetheless, several adsorbents have been shown to affect the use of nutrients and the absorption of minerals in poultry. Thus, seeking an effective strategy to counter or control embryotoxicity in broiler chicks caused by AFB1 is a problem. A total of 180 embryonated eggs were injected with 36 ng AFB1 with or without 5.90 mg L-methionine (Met) 30 embryonated eggs each, followed by incubation in an incubator until hatching time. The in ovo injection of Met significantly reduced toxicity caused by AFB1 in broiler embryos by enhancing the liver and kidney functions, lipid profiles, and alleviated oxidative stress during the incubation period. Furthermore, the relative gene expressions (SSTR5, TSH-β, Bcl-2, GSH-Px, GST-a, and SOD in the liver) were up-regulated with in ovo injection of AFB1+Met compared to AFB1 alone. Moreover, there was a dowin-regulated trend in Bax, Caspases-3, Caspases-7, Caspases-9, CYP1A1, CYP2H1, and P53 gene expression with in ovo injection of AFB1+Met compared to AFB1 alone. The in ovo injection of Met led to less apoptotic cells in liver tissues. Such results might be necessary for the poultry industry as it is focused on managing the embryotoxicity of AFB1, which affecting poultry production and welfare. Results from this study demonstrated that in ovo Met injection could alleviate AF-induced toxicity in chicken embryos.

Synergistic Antioxidant Effects of Araloside A and L-Ascorbic Acid on H2O2-Induced HEK293 Cells: Regulation of Cellular Antioxidant Status.

Araloside A is a pentacyclic triterpenoid saponin, and L-ascorbic acid is a globally recognized antioxidant. In this study, coadministered araloside A and L-ascorbic acid were found to have a strong synergistic antioxidant effect, and correlations between cellular antioxidant indexes and free radical scavenging ability were found. Individual and combined pretreatment with araloside A and L-ascorbic acid increased both cell viability and antioxidant enzyme activity and inhibited the release of lactate dehydrogenase (LDH); the accumulation of malondialdehyde (MDA), lipid peroxidation (LPO) products, and H2O2; and the production of intracellular reactive oxygen species (ROS), protein carbonyls, and 8-hydroxy-2-deoxy guanosine (8-OHdG). Free radical scavenging ability was positively correlated with superoxide dismutase (SOD) and catalase (CAT) activity, the glutathione (GSH)/oxidized glutathione (GSSG) ratio, and total antioxidant capacity (T-AOC). Our study is the first investigation of araloside A and L-ascorbic acid coadministration for the treatment of diseases caused by oxidative stress. The synergistic antioxidant effects of araloside A and L-ascorbic acid support their potential as functional food ingredients for the elimination of oxidative stress-induced adverse reactions.

Effects of caffeine on brain antioxidant status and mitochondrial respiration in acetaminophen-intoxicated mice.

Hepatic encephalopathy is a pathophysiological complication of acute liver failure, which may be triggered by hepatotoxic drugs such as acetaminophen (APAP). Although APAP is safe in therapeutic concentration, APAP overdose may induce neurotoxicity, which is mainly associated with oxidative stress. Caffeine is a compound widely found in numerous natural beverages. However, the neuroprotective effect of caffeine remains unclear during APAP intoxication. The present study aimed to investigate the possible modulatory effects of caffeine on brain after APAP intoxication. Mice received intraperitoneal injections of APAP (250mg/kg) and/or caffeine (20mg/kg) and, 4h after APAP administration, samples of brain and blood were collected for the biochemical analysis. APAP enhanced the transaminase activity levels in plasma, increased oxidative stress biomarkers (lipid peroxidation and reactive oxygen species), promoted an imbalance in endogenous antioxidant system in brain homogenate and increased the mortality. In contrast, APAP did not induce dysfunction of the mitochondrial bioenergetics. Co-treatment with caffeine modulated the biomarkers of oxidative stress as well as antioxidant system in brain. Besides, survival assays demonstrated that caffeine protective effects could be dose- and time-dependent. In addition, caffeine promoted an increase of mitochondrial bioenergetics response in brain by the enhancement of the oxidative phosphorylation, which could promote a better energy supply necessary for brain recovery. In conclusion, caffeine prevented APAP-induced biochemical alterations in brain and reduced lethality in APAP-intoxicated mice, these effects may relate to the preservation of the cellular antioxidant status, and these therapeutic properties could be useful in the treatment of hepatic encephalopathy induced by APAP intoxication.

Melatonin induced suppression of ER stress and mitochondrial dysfunction inhibited NLRP3 inflammasome activation in COPD mice

In recent decades, the occurrence of chronic obstructive pulmonary disease (COPD) has been increased remarkably in the population. Cigarette smoke (Cs) plays one of the key roles for COPD development. In our study, we explored the ameliorative role of melatonin on COPD progression by using a Cs inhaled in vivo COPD and cigarette smoke extract (CSE)-treated in vitro L-132 (alveolar epithelial cell) models. Mice exposed to Cs (4hr/day for 4 weeks) exhibited abrupt increase of lactate dehydrogenase (LDH) level in broncho alveolar lavage fluid (BALF) and disrupted alveolar structure in lung tissue. Additionally, increased reactive oxygen species (ROS), decreased cellular antioxidant status with reduced GSH/GSSG ratio were also found in Cs exposed lung. Besides, Cs induced endoplasmic reticulum (ER) stress and mitochondrial dysfunctions causing the activation of NLRP3 inflammasome. Activated NLRP3 inflammasome caused Caspase-1 mediated release of IL-1β and IL-18 resulting in inflammatory outburst. Melatonin showed protection against COPD both in vitro and in vivo. Exhibiting its anti-inflammatory potential, melatonin also attenuated the lung inflammation. It activated the intracellular antioxidant Thioredoxin-1 (thereby suppressing the TXNIP/NLRP3 pathway) and inhibited the impaired mitophagy mediated inflammasome activation (upregulating PINK-1, Parkin, LC3B-II expression). Melatonin also improved the overall antioxidant status of the COPD lung via NRF-2-HO-1 axis restoration.