GST) And Glutathione Research Articles

Consumption of toxic benthic cyanobacteria by two common demersal fish: Growth, antioxidant and liver histopathology responses

Benthic freshwater cyanobacteria have the potential to produce toxins. Compared with more extensively studied plankton species, little is known about the impact of harmful benthic cyanobacteria on aquatic organisms. As demersal fish are usually in direct contact with benthic cyanobacteria, it is important to understand their interactive effects. This study investigated the physio-chemical responses of two demersal fish (Xenocypris davidi and Crucian carp) after exposure to benthic Oscillatoria (producing cylindrospermopsin, 2 × 106 cells/mL) for 7 days. Interestingly, benthic Oscillatoria had less adverse effects on X. davidi than C. carp. The two demersal fish effectively ingested Oscillatoria, but Oscillatoria cell sheathes could not be fully digested in C. carp intestines and led to growth inhibition. Oscillatoria consumption induced oxidative stress and triggered alterations in detoxification enzyme activities in the X. davidi liver. Superoxide dismutase (SOD) and glutathione reductase (GR) activities significantly increased in the C. carp liver, but catalase (CAT) and detoxification enzymes glutathione S-transferase (GST) and glutathione (GSH) activities were insignificantly changed. This suggested that C. carp may have a relatively weak detoxification capacity for toxic Oscillatoria. Oscillatoria ingestion led to more pronounced liver pathological changes in C. carp, including swelling, deformation, and loss of cytoskeleton structure. Simultaneously, fish consumption of Oscillatoria increased extracellular cylindrospermopsin concentration. These results provide valuable insights into the ecological risks associated with benthic cyanobacteria in aquatic ecosystems.

Toxic Impact of Dietary Cadmium on Bioaccumulation, Growth, Hematological Parameters, Plasma Components, and Antioxidant Responses in Starry Flounder (Platichthys stellatus)

Starry flounders (Platichthys stellatus) (average weight—114.69 ± 13 g, length—19.0 ± 0.21 cm) underwent a 4-week exposure to varying dietary cadmium (Cd) concentrations: 0, 10, 20, 40, 60, and 80 mg/kg. Bioaccumulation patterns were revealed in the intestine, kidney, liver, and gills in descending order of accumulation. Significant declines in growth indicators—body weight gain (BWG), specific growth rate (SGR), and feed efficiency ratio percentage (FER)—were evident at 80 mg Cd/kg for 2 weeks and beyond 60 mg Cd/kg for 4 weeks. Hematological parameters, including red blood cell (RBC) count, hematocrit (Ht), and hemoglobin (Hb), remarkably reduced at 80 mg Cd/kg for both 2 and 4 weeks. The total plasma protein reduced significantly after exposure to Cd for 2 and 4 weeks, alongside increased glucose levels, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvate transaminase (GPT). Considerable increases in antioxidant responses—superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione (GSH) levels—were observed after exposure to Cd for 2 and 4 weeks. P. stellatus exhibits a high accumulation of dietary Cd in specific tissues. Moreover, concentrations above 60 mg Cd/kg adversely affected the growth performance, hematological parameters, plasma components, and antioxidant responses.

Weissella confusa MW051433 and Levilactobacillus brevis MW362788 of human milk origin possess antioxidant competency: In vivo evidence

Consumption of high-fat diet (HFD) is directly associated with oxidative stress (OS), a root cause of metabolic disorders while probiotics have been recently recognized to play important role in OS management. The current study describes the antioxidant potential of well characterized and least explored probiotics, Levilactobacillus brevis MW362788 and Weissella confusa MW051433 isolated from human milk. Wistar rats were exposed to HFD to induce OS and treated with W. confusa MW051433, L. brevis MW 362788 and their mixture. W. confusa MW051433 treatment led to amelioration of OS as depicted by improvement in Malondialdehyde (MDA), Total oxidant status (TOS), Total antioxidant status (TAS), Superoxide dismutase (SOD), Catalase (CAT), Glutathione-S-transferase (GST), and Glutathione (GSH) in serum, liver, kidney, and brain. The L. brevis MW362788 administration restored MDA, SOD (serum, liver, kidney), TOS (serum, kidney), TAS (serum, liver, kidney, brain), GST (liver), GSH (kidney, brain) but could not influence CAT activity in any organ. While administration of their mixture could customize MDA, TAS (serum, liver, kidney, brain), TOS, SOD, CAT (serum, liver, kidney), GST (serum, liver), and GSH (serum, kidney, brain). The OS modulation was strain specific and the promising antioxidant behavior of W. confusa MW051433 signatures its bio therapeutic potential.

Toxic effects of sub-acute microplastic (polyamide) exposure on the accumulation, hematological, and antioxidant responses in crucian carp, Carassius carassius

The purpose of this study is to investigate the impact of microplastics (MPs) on fish and to confirm the toxic effects of MPs on fish, as well as to clarify the standard indicators. MPs are present in a large amount in the aquatic environment and can have various adverse effects on aquatic animals. Crucian carp, Carassius carassius (mean weight, 23.7 ± 1.6 g; mean length, 13.9 ± 1.4 cm), were exposed to PA (Polyamide) concentrations of 0, 4, 8, 16, 32 and 64 mg/L for 2 weeks. The PA accumulation profile in C. carassius decreased from the intestine to the gill to the liver. Hematological parameters such as red blood cell (RBC) counts, hemoglobin (Hb), and hematocrit (Ht) notably decreased at high levels of PA exposure. Plasma components such as calcium, magnesium, glucose, cholesterol, total protein, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were significantly altered by PA exposure. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and glutathione (GSH) of liver, gill and intestine significantly increased following PA exposure. The results of this study suggest that MP exposure affects the hematological physiology and antioxidant responses in C. carassius as well as accumulation in specific tissues.

The mercury accumulation and its effects on antioxidant and immune responses in starry flounder, Platichthys stellatus exposed to dietary mercury

The purpose of this study is to investigate the effect of inorganic mercury (Hg) on fish. Inorganic Hg is less toxic than organic Hg, but it is used more in human daily life, such as manufacturing Hg batteries and fluorescent lamps. For this reason, inorganic Hg was used in this study. Starry flounder, Platichthys stellatus (mean weight 43.9 ± 4.4 g; mean length 14.2 ± 0.4 cm) were exposed for 4 weeks to the different levels of dietary inorganic Hg at concentrations of 0, 4, 8, 12 and 16 mg Hg/kg, and depuration was performed for 2 weeks after exposure. Bioaccumulation of Hg in the tissues was observed to increase significantly, in following order: intestine > head kidney > liver > gills > muscle. Antioxidant responses (superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST) and glutathione (GSH)) were significantly increased. Immune responses (lysozyme and phagocytosis activity) were substantially decreased. The results of this study suggest that dietary inorganic Hg induces bioaccumulation in specific tissues, increases antioxidant responses and decreases immune responses. After the depuration period for 2 weeks, it was effective to alleviate bioaccumulation in tissues. However, antioxidant and immune responses were limited to be attenuated for recovery.

Effect of Glutamine on the Growth Performance, Oxidative Stress, and Nrf2/p38 MAPK Expression in the Livers of Heat-Stressed Broilers

The purpose of this work was to study the effects of glutamine (Gln) on the growth performance, oxidative stress, Nrf2, and p38 MAPK pathway in the livers of heat-stressed broilers. In total, 300 broilers were divided into five groups, including a normal temperature (NT, without dietary Gln) group and four cyclic high temperature groups (HT, GHT1, GHT2, and GHT3) fed with 0%, 0.5%, 1.0%, and 1.5% Gln, respectively. High temperature conditions increased (p < 0.05) liver malonaldehyde (MDA) concentration, but decreased (p < 0.05), body weight gain (BWG), feed intake (FI), liver superoxide dismutase (SOD), total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), and glutathione (GSH) levels in broilers. Nrf2 and p38 MAPK protein and mRNA expression levels were lower (p < 0.05) in the NT group than that in the HT group. However, dietary 1.5% Gln decreased (p < 0.05) liver MDA concentration, but increased (p < 0.05) BWG, FI, liver SOD, T-AOC, GSH-Px, GST, and GSH levels in heat-stressed broilers. Nrf2 and p38 MAPK protein and mRNA expression levels were higher (p < 0.05) in the GHT3 group than that in the HT group. In summary, Gln improved oxidative damage through the activation of Nrf2 and p38 MAPK expression in the livers of heat-stressed broilers.

Zeaxanthin attenuates OVA-induced allergic asthma in mice by regulating the p38 MAPK/β-catenin signaling pathway

Background: Asthma is a heterogeneous and complex chronic airway disease with a high incidence rate, characterized by chronic airway inflammation. Although the anti-inflammatory effect of zeaxanthin has been demonstrated in various disease models, its explicit role in allergic asthma remains elusive. Methods: An allergic asthma model was established by ovalbumin (OVA) stimulation in BALB/c nude mice. The pathological examination, collagen deposition and expression of α-smooth muscle actin (α-SMA) in lung tissues were determined by hematoxylin and eosin (H&amp;E), MASSON and immunofluorescence staining, respectively. Besides, the effect of zeaxanthin on inflammation and oxidative stress was assessed by the enzyme-linked immunosorbent assay (ELISA) and spectrophotometry measure. Moreover, the underlying mechanism was analyzed by detecting the expression of phosphorylated p38 (p-p38), p38, β-catenin, p-c-Jun N-terminal kinase (p-JNK) and JNK with western blot assays. Results: The distinct infiltration of inflammatory cells was observed in the OVA-induced asthma mice model with significantly increased concentrations of immunoglobulin E (IgE), interleukin-4 (IL-4), IL-5, IL-13 and eotaxin (p˂0.001), which were prominently reversed by zeaxanthin treatment (p˂0.001). In addition, zeaxanthin treatment decreased the OVA-induced collagen deposition and α-SMA expression. A similar inhibitory effect of zeaxanthin on the oxidative stress was also observed in the OVA-induced asthma mice model, as evidenced by the prominent decrease of malondialdehyde (MDA) concentration and the remarkable increase of superoxide dismutase (SOD), glutathione S transferase (GST) and Glutathione (GSH) concentrations (p˂0.001). Moreover, zeaxanthin introduction markedly reduced the relative expressions of p-p38/p38, β-catenin and p-JNK/JNK in the OVA-induced asthma mice model (p˂0.001), indicating that zeaxanthin suppressed the p38 mitogen-activated protein kinase (p38 MAPK)/β-catenin signaling pathway in the OVA-induced asthma mice model. Conclusions: Zeaxanthin attenuated OVA-induced allergic asthma in mice via modulating the p38 MAPK/β-catenin signaling pathway.

Embryonic exposure to butylparaben and propylparaben induced developmental toxicity and triggered anxiety‐like neurobehavioral response associated with oxidative stress and apoptosis in the head of zebrafish larvae

Parabens are synthetic antimicrobial compounds used as a preservative for extending the shelf life of food, pharmaceutical and cosmetic products. The alkyl chain length of the paraben esters positively correlates with their antimicrobial property. Hence, long-chain paraben esters, namely butylparaben and propylparaben, are used in combination as they have better solubility and antimicrobial efficacy. Extensive use of parabens has now resulted in the ubiquitous presence of these compounds in various human and environmental matrices. During early life, exposure to environmental contaminants is known to cause oxidative-stress mediated apoptosis in developing organs. The brain being one of the high oxygen-consuming, metabolically active and lipid-rich organ, it is primarily susceptible to reactive oxygen species (ROS) and lipid peroxidation (LP) induced neuronal cell death. The primary cause for the impairment in cognitive and emotional neurobehvioural outcomes in neurodegenerative disease was found to be associated with neuronal apoptosis. The present study aimed to study butylparaben and propylparaben's effect on zebrafish during early embryonic stages. Besides this, the association between alteration in anxiety-like neurobehavioral response with oxidative stress and antioxidant status in head region was also studied. The study results showed variation in the toxic signature left by butylparaben and propylparaben on developmental parameters such as hatching rate, survival and non-lethal malformations in a time-dependent manner. Data from the light-dark preference test showed embryonic exposure to butylparaben and propylparaben to trigger anxiety-like behavior in zebrafish larvae. In addition, a significant increase in intracellular ROS and LP levels correlated with suppressed antioxidant enzymes: superoxide dismutases (SOD), catalases (CAT), Glutathione peroxidase (GPx), glutathione S-transferase (GST), and Glutathione (GSH) activity in the head region of the zebrafish larvae. Acetylcholinesterase (AChE) activity was also suppressed in the exposed groups, along with increased nitric oxide production. The overall observations show increased oxidative stress indices correlating with upregulated expression of apoptotic cells in a dose-dependent manner. Collectively, our findings reveal butylparaben and propylparaben as an anxiogenic neuroactive compound capable of inducing anxiety-like behavior through a mechanism involving oxidative-stress-induced apoptosis in the head of zebrafish larvae, which suggests a potential hazard to the early life of zebrafish and this can be extrapolated to human health as well.

Evaluation of Tribulus terrestris Extracts Relative to Metformin on Oxidative Stress and Histopathology of the Liver for Diabetic Male Rats

Insulin-dependent diabetes mellitus (IDDM) is a metabolic condition that induces blood glucose levels to rise due to insulin deficiency and the formation of reactive oxygen species (ROS). The purpose of this study is to assess how efficient the antioxidant extracts Tribulus terrestris (TT) and metformin (MET) are in reducing oxidative stress and histopathology produced by streptozotocin in rat hepatocytes. The 36 male rats weighing 170–190 g of this study were randomly sorted into 6 groups. The first group was considered a normal control group, and the second and third groups were normal and remedy with MET and TT extract, respectively. The fourth group was positive diabetic, and the fifth and sixth groups were diabetic rats that were treated with MET and TT extract, respectively. Lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST), and glutathione (GSH) were detected, and the histopathology of the liver was evaluated after 8 weeks of treatment. Compared to regulation, morphological changes in the liver were found in diabetic animals, with a rise in LPO and a change in GSH levels as well as CAT and GST activities. The oxidative stress and histological architecture of the hepatocytes caused by hyperglycemia were improved as a result of therapy in the rats with MET and TT extract. Because of its antioxidant activities, diabetic rats with TT extract are more effective than MET in normoglycemia and hepatocyte reconditioning. Beneficial intervention tends to benefit primarily from direct ROS scavenging and CAT, GST, and GSH regeneration.

Tangeretin ameliorates bisphenol induced hepatocyte injury by inhibiting inflammation and oxidative stress

Bisphenol A (BPA) is an industrial toxicant that can potentially damage the liver. Tangeretin (TGN) is a natural flavonoid that displays various pharmacological activities. This experiment was carried out to evaluate the protective effects of TGN against BPA-induced hepatic impairment in the male albino rat. Twenty-four male albino rats were equally divided into four different groups: control, BPA (100 mg/kg), BPA + TGN (100 mg/kg + 50 mg/kg) and TGN (50 mg/kg). BPA exposure significantly decreased the activities of catalase (CAT), superoxidase dismutase (SOD), peroxidase (POD), glutathione reductase (GSR), glutathione S-transferase (GST), and glutathione (GSH) content while substantially increasing the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels. A substantial increase in the levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) was also observed in BPA treated rats. Moreover, BPA significantly increased the inflammatory markers, including tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB), Interleukin-6 (IL-6), Interleukin-1β (IL-1β)levels, cyclooxygenase-2 (COX-2) activity, and histopathological damages. However, co-treatment with TGN efficiently minimized the BPA-induced biochemical, inflammatory, and histopathological impairments in rat liver. The present study shows that TNG has significant potential to avert BPA-induced liver damage to its antioxidant and anti-inflammatory properties.

Pomegranate juice moderates anxiety- and depression-like behaviors in AlCl3-treated male mice

PurposeAluminum trichloride (AlCl3) exposure was proven to encourage some behavioral deficits and eventually induces anxiety and depression in rodents animals. Therefore, this experiment aimed to scout about the effects of pomegranate juice on anxiety- and depression-like behaviors caused by AlCl3 in male mice. MethodsSix groups of male mice were administrated orally for 35 days by PJ and AlCl3. The control group (G-I) received tap water, while the PJ groups (G-II and G-III) were treated with 20 % and 40 % PJ, respectively. The AlCl3 group (G-IV) was treated with 400 mg/kg/day of AlCl3, and the last two groups (G-V and G-VI) were treated with AlCl3 and 20 % PJ or 40 % PJ, respectively. Then, the open-field (O-F), elevated plus maze (EPM), tail suspension (TS), forced swimming (FS), and light/dark box (L/DB) tests were applied for anxiety- and depression-like behavior studies. In addition, neurotransmitters and oxidative parameters in the brain were evaluated. The plasma cortisol was measured at the end of the experiment. ResultsBehavioral analyses showed that PJ inhibited AlCl3-induced depressive and anxiogenic effects in the O-F, EPM, TS, FS, L/DB tests. In addition, neurochemical results indicated that PJ at 20 % concentration minimized the AlCl3 toxicity on dopamine (DOP), serotonin (SER), and acetylcholinesterase (AChE) levels in the for-brain of male mice. Moreover, PJ moderated the AlCl3 effects by decreasing the level of thiobarbituric acid reactive substances (TBARS), and enhancing catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST) and glutathione (GSH) activities. The plasma cortisol increased in male mice treated with AlCl3 and in a group treated with a high dose of PJ. ConclusionOur results proposed that the anxiety- and depression-like behaviors induced by AlCl3 exposure in male mice can be ameliorated by PJ treatment, probably through the inhibition of oxidative damage and minimizing the changes in neurotransmitters and hormonal activity.

Carveol Attenuates Seizure Severity and Neuroinflammation in Pentylenetetrazole-Kindled Epileptic Rats by Regulating the Nrf2 Signaling Pathway.

Epilepsy is a neurodegenerative brain disorder characterized by recurrent seizure attacks. Numerous studies have suggested a strong correlation between oxidative stress and neuroinflammation in several neurodegenerative disorders including epilepsy. This study is aimed at investigating the neuroprotective effects of the natural compound carveol against pentylenetetrazole- (PTZ-) induced kindling and seizure model. Two different doses of carveol (10 mg/kg and 20 mg/kg) were administered to male rats to determine the effects and the effective dose of carveol and to further demonstrate the mechanism of action of nuclear factor E2-related factor (Nrf2) in PTZ-induced kindling model. Our results demonstrated reduced levels of innate antioxidants such as superoxide dismutase (SOD), catalase, glutathione-S-transferase (GST), and glutathione (GSH), associated with elevated lipid peroxidation (LPO) and inflammatory cytokines level such as tumor necrosis factor-alpha (TNF-α), and mediators like cyclooxygenase (COX-2) and nuclear factor kappa B (NFκB). These detrimental effects exacerbated oxidative stress and provoked a marked neuronal alteration in the cortex and hippocampus of PTZ-intoxicated animals that were associated with upregulated Nrf2 gene expression. Furthermore, carveol treatment positively modulated the antioxidant gene Nrf2 and its downstream target HO-1. To further investigate the role of Nrf2, an inhibitor of Nrf2 called all-trans retinoic acid (ATRA) was used, which further exacerbated PTZ toxicity. Moreover, carveol treatment induced cholinergic system activation by mitigating acetylcholinesterase level which is further linked to attenuated neuroinflammatory cascade. The extent of blood-brain barrier disruption was evaluated based on vascular endothelial growth factor (VEGF) expression. Taken together, our findings suggest that carveol acts as an Nrf2 activator and therefore induces downstream antioxidants and mitigates inflammatory insults through multiple pathways. This eventually alleviates PTZ-induced neuroinflammation and neurodegeneration.

Antioxidant responses in cyanobacterium Microcystis aeruginosa caused by two commonly used UV filters, benzophenone-1 and benzophenone-3, at environmentally relevant concentrations

Benzophenone-type ultraviolet filters (BPs) have recently been recognized as emerging organic contaminants. In the present study, the cyanobacterium Microcystis aeruginosa was exposed to environmentally relevant levels (0.01-1000 μg L-1) of benzophenone-1 (BP-1) and benzophenone-3 (BP-3) for seven days. A battery of tested endpoints associated with photosynthetic pigments and oxidative stress was employed for a better understanding of the mode of action. The tested cyanobacterium could uptake the two BPs (27.4-54.9%) from culture media. The two BPs were able to inhibit the production of chlorophyll a (chl-a) and promote the accumulation of carotenoids, leading to unaffected chl-a autofluorescence. Slightly increased malondialdehyde (MDA) contents suggested that BP-1 and BP-3 caused moderate oxidative stress. BP-1 stimulated the activities of superoxide dismutase (SOD), glutathione reductase (GR) and glutathione S-transferase (GST) in M. aeruginosa while BP-3 increased the activities of SOD, GST, and glutathione (GSH), showing a concentration- and time-dependent relationship. The activities of other biomarkers, such as catalase (CAT) and glutathione peroxidase (GPx) fluctuated depending on exposure time and concentration. The overall results suggested that the two BPs can trigger moderate oxidative stress in M. aeruginosa and the tested cyanobacterium was capable of alleviating stress by different mechanisms.

Detoxifying effects of optimal hyperoxia (40% oxygenation) exposure on benzo[a]pyrene-induced toxicity in human keratinocytes

ABSTRACTDetoxifying effects of hyperoxia, which is widely used in clinical practice, were investigated using HaCat cells (human keratinocytes) treated with benzo[a]pyrene (B[a]P) as a model agent to induce adverse effects in the skin. It is well-established that B[a]P may produce toxicities including cancer, endocrine disruption, and phototoxicity involving DNA damage, free radical generation, and down regulation of nuclear factor erythroid 2-related factor 2 (Nrf2). It is well-known that Nrf2 is associated increase of antioxidant enzyme catalase (CAT) or detoxification enzyme glutathione S-transferase (GST) in HaCat cells treated with B[a]P under optimal condition of hyperoxia (40% oxygenation) conditions. To further examine the underlying basis of this phenomenon, factors affecting the expression of Nrf2 were determined. Nrf2 was upregulated accompanied by a rise in p38 MAPK, sequestosome-1 (also known as p62) and NF-κB. In contrast, Nrf2 was downregulated associated with an elevation in glycogen synthase kinase 3 beta (GSK-3β) and peroxisome proliferator-activated receptor alpha (PPARα). Hyperoxia was also found to diminish DNA damage and generation of free radicals initiated in B[a]P-treated cells which was attributed to an significant rise of Nrf2, leading to elevated antioxidant activities or detoxification proteins including heme oxygenase 1 (HO-1), superoxide dismutase (SOD), glutathione peroxidase-1/2 (GPX-1/2), CAT, GST and glutathione (GSH). In addition, factors related to skin aging were also altered by hyperoxia. Data suggest that optimal hyperoxia exposure of 40% oxygenation may reduce cellular toxicity induced by B[a]P in HaCat cells as evidenced by inhibition of DNA damage, free radical generation, and down-regulation of Nrf2.

Study on lipid peroxidation and In vivo antioxidant activity of various extract of Dyschoriste littoralis nees on paracetamol-induced hepatotoxicity rats

The current investigation was to examine the antioxidant potential of D.littoralis Nees. (family Acanthaceae) On paracetamol-induced hepatotoxicity in rats. The aerial parts of D.littoralis Nees. The powder was concentratesed with various solvents (PE, EA, and methanol) through Soxhlet concentrates and various crude concentrates utilized for hepatoprotective activity. Hepatotoxicity was induced by paracetamol (2g/kg b.wt.) on the 5th day of the investigational period and given orally. Paracetamol-induced rats to exhibit elevated activities of TBARS and reduction the enzymes levels such as Superoxide dismutase(SOD), catalase(CAD), Glutathione peroxidise (GPx), Glutathione S transferase(GST) and Glutathione (GSH) in liver and kidney. Furthermore, Oral administration of the ethyl acetate concentrates of D.littoralis (200 mg/ kgb.wt.) given rats were major reduction the level of TBARS and also significantly elevated the levels of the enzyme such as Superoxide dismutase(SOD), catalase(CAD), Glutathione peroxidise(GPx), Glutathione S transferase(GST) and Glutathione (GSH) in liver and kidney as compared to other concentrates. Thus, results suggested that ethyl acetate concentrates of D.littoralis could be afford better antioxidant effect against paracetamol-induced hepatotoxicity rats.

Nanosized selenium and Loranthus micranthus leaves ameliorate streptozotocin-induced hepato-renal dysfunction in rats via enhancement of antioxidant system, regulation of caspase 3 and Nrf2 protein expression

The investigation of potential health benefits of nano-sized nutriceuticals is recently a major scientific interest. The present study investigated the effect of Selenium and Loranthus micranthus leaves nanoparticles (SeNPs and LMLNPs), on streptozotocin (STZ)-diabetes induced hepato-renal dysfunction in rats. Adult rats were rendered diabetic by a single i.p exposure to 40 mg/kg STZ. Thereafter, rats were treated with 0.1 mg/kg SeNPs or 200 mg/kg LMLNPs, or a combination of both, while 50 mg/kg metformin was used as a standard therapeutic drug. Results indicated that STZ-diabetic rats experienced liver and kidney damage evidenced by a significant elevation in serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and 5′ nucleotidase (5′NT) when compared to non-diabetic control rats. Furthermore, a decrease in activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), Glutathione-S-transferase (GST) and glutathione (GSH) levels was observed, whereas myeloperoxidase (MPO) activities and lipid peroxidation (LPO) levels increased significantly in the negative control group compared to the test groups. Immunohistochemical and western blot analyses showed a corresponding elevation in the expression of apoptotic biomarker-caspase 3 and nuclear erythroid 2-related factor 2 (Nrf2) protein in STZ-diabetes group relative to the test groups. SeNPs and/or LMLNPs significantly ameliorated the various alterations imposed by STZ-diabetes relative to the control group. The chemotherapeutic influence in STZ-diabetic rats could be elicited via augmentation of antioxidant defence systems, regulation of Nfr2 expression, decrease in lipid peroxidation and regulation of apoptosis in the studied tissues.

Mapping ligand binding using microfluidics-enabled millisecond timescale hydrogen-deuterium exchange

Hydrogen Deuterium eXchange (HDX) is rapidly emerging as a key technique for characterizing changes in dynamics that accompany protein complexation and ligand binding. Binding site mapping is an important application of HDX, however, artifacts from allosteric effects often introduce ambiguity into the results. We have previously developed a microfluidic device that incorporates a complete ‘bottom-up’ HDX workflow with rapid mixing for time-resolved (millisecond time-scale) labelling. Here, we evaluate this approach for mapping ligand-binding using the well-characterized interaction between glutathione-S-Transferase (GST) and glutathione (GSH). In a rapid analysis, significant decreases in dynamics were mapped exclusively to the GST active site region and specifically to segments that make direct contact with GSH via backbone hydrogen bonding. Importantly, artifacts from allostery were not apparent in the time-resolved HDX data. We conclude that time-resolved HDX could provide a powerful approach for mapping ligand binding sites and capturing the evolution of protein dynamics after protein/ligand complexation.

A Study on Cytotoxic and Apoptotic Potential of a Triterpenoid Saponin (3-O-α-L-Arabinosyl Oleanolic Acid) Isolated fromSchumacheria castaneifoliaVahl in Human Non-Small-Cell Lung Cancer (NCI-H292) Cells

Lung cancer is the major cause of cancer death among men. A number of natural compounds have proven to be useful in the treatmet of lung cancer. This study was aimed to determine cytotoxic and apoptotoic effects of a natural compound 3-O-α-L-arabinosyl oleanolic acid (3-O-L-AO) isolated from Schumacheria castaneifolia in non-small-cell lung cancer (NCI-H292) cells. Cytotoxic effects of 3-O-L-AO were determined by Sulforhodamine B (SRB) assay and apoptotic effects were tested by evaluating (a) apoptotsis related morphological changes, (b) caspase 3/7 activity, and (c) expression of Bax, p53, and survivin genes. Oxidative stress markers (reactive oxygen species (ROS), glutathione-S-transferase (GST), and glutathione (GSH)) were also analysed in 3-O-L-AO treated NCI-H292 cells. 3-O-L-AO exerted potent cytotoxic effects in NCI-H292 cells while being less cytotoxic to normal lung (MRC-5) cells. Exposure to 3-O-L-AO caused upregulation of Bax and p53 and downregulation of survivin in NCI-H292 cells. Activation of caspase 3/7 and morphological features related to apoptosis further confirmed 3-O-L-AO induced apoptosis. Furthermore, elevated ROS and GST levels and decreased GSH levels suggested 3-O-L-AO can induce apoptosis, possibly causing oxidative stress in NCI-H292 cells. Overall results suggest that 3-O-L-AO can be considered as an effective anticancer agent for the treatment of lung cancer.

Effects of sub-chronic exposure to lead (Pb) and ascorbic acid in juvenile rockfish: Antioxidant responses, MT gene expression, and neurotransmitters

Juvenile rockfish Sebastes schlegelii were exposed to varying levels of dietary lead (Pb2+) at 0, 120 and 240 mg/L, and ascorbic acid (AsA) at 100, 200 and 400 mg/L for four weeks. Antioxidant responses such as superoxide dismutase (SOD), glutathione S-transferase (GST), and glutathione (GSH) were analyzed to assess oxidative stress. SOD and GST activity in the liver and gills were considerably elevated by dietary Pb. In contrast, GSH levels in the liver and gills were significantly reduced following Pb exposure. High levels of AsA supplementation attenuated the increase in SOD and GST activity and reduction in GSH levels. The metallothionein gene (MT) in the liver was notably stimulated by Pb exposure, and AsA supplementation attenuated this increase. With respect to neurotoxicity, acetylcholinesterase (AChE) activity was substantially inhibited in the brain and muscle following Pb exposure. AsA supplementation also attenuated AChE inhibition following Pb exposure. The results of this study presented Pb exposure affected rockfish as toxicity, and AsA was effective to alleviate toxic effects of Pb.

Effect of Acetone on Reactive Oxygen Species to Mice Skin

Acetone is one of the organic solvents that causes skin barrier disruption such as eczema and dermatitis, ichthyosis and xerosis, and ROS (reactive oxygen species) paly a role of skin toxicity. This study is focused on investigating the effect of ROS of applied acetone. Acetone was applied to mice skin (0.25ml/㎠) four times (6h, 12h, 18h, 24h) every day for two or four days. Increased activity of acid phosphatase (ACP) and increased content of lipid peroxide (LPO) in acetone was determined in the applied group for four days(4ACE) compared with the acetone applied group for two days (2ACE). As for the ROS generating enzymes, one of them, xanthine oxidase (XO) showed no differences between control and 2ACE despite the significantly different 4ACE. There were some differences between 2ACE and 4ACE on the activities of cytochrome P450 dependent aniline hydroxylase (CYPdAH), which seemed to be the increased rates of acetone metabolites. There were more decreased rates of the activities of ROS scavenging enzymes, glutathione peroxidase (GPx), catalase (CAT), superoxide dismutae (SOD), glutathione S-transferase (GST), and glutathione (GSH) contents in 4ACE compared with 2ACE. The results indicate that the damaged skin tissue could cause unbalance of the ROS generating system and scavenging system by the frequent exposure of acetone application.