Total Glutathione Content Research Articles

N-Acetylcysteine Reverses the Mitochondrial Dysfunction Induced by Very Long-Chain Fatty Acids in Murine Oligodendrocyte Model of Adrenoleukodystrophy.

The accumulation of saturated very long-chain fatty acids (VLCFA, ≥C22:0) due to peroxisomal impairment leads to oxidative stress and neurodegeneration in X-linked adrenoleukodystrophy (ALD). Among the neural supporting cells, myelin-producing oligodendrocytes are the most sensitive to the detrimental effect of VLCFA. Here, we characterized the mitochondrial dysfunction and cell death induced by VLFCA, and examined whether N-acetylcysteine (NAC), an antioxidant, prevents the cytotoxicity. We exposed murine oligodendrocytes (158 N) to hexacosanoic acid (C26:0, 1–100 µM) for 24 h and measured reactive oxygen species (ROS) and cell death. Low concentrations of C26:0 (≤25 µM) induced a mild effect on cell survival with no alterations in ROS or total glutathione (GSH) concentrations. However, analysis of the mitochondrial status of cells treated with C26:0 (25 µM) revealed depletion in mitochondrial GSH (mtGSH) and a decrease in the inner membrane potential. These results indicate that VLCFA disturbs the mitochondrial membrane potential causing ROS accumulation, oxidative stress, and cell death. We further tested whether NAC (500 µM) can prevent the mitochondria-specific effects of VLCFA in C26:0-treated oligodendrocytes. Our results demonstrate that NAC improves mtGSH levels and mitochondrial function in oligodendrocytes, indicating that it has potential use in the treatment of ALD and related disorders.

Protofibril formation: decreased total glutathione concentration as an early indicator of neuron damage in the brainstems of Wistar rats treated with rotenone

Background: Rotenone treatment causes oxidative stress in neurons and forms the basis of animal models of Parkinson's disease. The reduced form of glutathione is predicted to detoxify rotenone from neurons in the brainstem. This study aims to measure the concentration of total glutathione and analyze the formation of protofibril in the brainstem of Wistar rats treated with rotenone. Methods: Seventy-two male Wistar rats aged 8–9 weeks weighing 200–250 g were divided into two investigations: total glutathione determination and protofibril analysis. The independent variables were treatment group, observation time, and location in the brainstem. The dependent variables were the concentration of total glutathione and protofibril density. Results: The concentration of total glutathione was not significantly different among treatment groups (p: 0.084), observation time (p: 0.608), or the location in the brainstem (p: 0.372). Protofibril density was different in the treatment groups (p: 0.001), observation time (p: 0.001), and between the upper and lower brainstem (p: 0.001). Rotenone treatment subcortically induced the concentration of total glutathione in the brainstem to decrease, but protofibril density tended to increase. Conclusions: The total glutathione concentration is inversely proportional to protofibril density. Total glutathione might be an early marker of neuronal damage.

Oil-mediated oxidative-stress responses in a keystone zooplanktonic species, Calanus finmarchicus

The copepod Calanus finmarchicus is an ecologically important species in the North Atlantic, Norwegian and Barents seas. Accidental or continuous petroleum pollution from oil and gas production in these seas may pose a significant threat to this low trophic level keystone species.Responses related to oxidative stress, protein damage and lipid peroxidation were investigated in C. finmarchicus exposed to a water-accommodated fraction (WAF) of a naphthenic North Atlantic crude oil. The exposure concentration corresponded to 50% of the 96 h LC50, and samples were obtained at 0, 24, 48, 72 and 96 h after exposure initiation. Gene expressions (superoxide dismutase, catalase, glutathione S-transferase, glutathione synthetase, heat shock protein 70 and 90, ubiquitin and cytochrome P-450 330A1), enzyme activities (superoxide dismutase, catalase, glutathione S-transferase) and concentrations of total glutathione and malondialdehyde were analyzed. Gene expression analyses showed no differences between controls and the exposed animals, however significantly higher glutathione S-transferase activity and malondialdehyde concentrations were found in the exposed group, suggests lipid peroxidation as main toxic effect.

Anoxia-reoxygenation modulates cadmium-induced liver mitochondrial reactive oxygen species emission during oxidation of glycerol 3-phosphate

Aquatic organisms are frequently exposed to multiple stressors including low dissolved oxygen (O2) and metals such as cadmium (Cd). Reduced O2 concentration and Cd exposure alter cellular function in part by impairing energy metabolism and dysregulating reactive oxygen species (ROS) homeostasis. However, little is known about the role of mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) in ROS homeostasis in fish and its response to environmental stress. In this study, mGPDH activity and the effects of anoxia-reoxygenation (A-RO) and Cd on ROS (as hydrogen peroxide, H2O2) emission in rainbow trout liver mitochondria during oxidation of glycerol 3-phosphate (G3P) were probed. Trout liver mitochondria exhibited low mGPDH activity that supported a low respiratory rate but substantial H2O2 emission rate. Cd evoked a low concentration stimulatory-high concentration inhibitory H2O2 emission pattern that was blunted by A-RO. At specific redox centers, Cd suppressed H2O2 emission from site IQ, but stimulated emission from sites IIIQo and GQ. In contrast, A-RO stimulated H2O2 emission from site IQ following 15 min exposure and augmented Cd-stimulated emission from site IIF after 30 min exposure but did not alter the rate of H2O2 emission from sites IIIQo and GQ. Additionally, Cd neither altered the activities of catalase, glutathione peroxidase, or thioredoxin reductase nor the concentrations of total glutathione, reduced glutathione, or oxidized glutathione. Overall, this study indicates that oxidation of G3P drives ROS production from mGPDH and complexes I, II and III, whereas Cd directly modulates redox sites but not antioxidant defense systems to alter mitochondrial H2O2 emission.

Wheat Leaf Antioxidative Status-Variety-Specific Mechanisms of Zinc Tolerance during Biofortification.

In this study, we evaluated the leaf antioxidative responses of three wheat varieties (Srpanjka, Divana, and Simonida) treated with two different forms of zinc (Zn), Zn-sulfate and Zn-EDTA, in concentrations commonly used in agronomic biofortification. Zn concentration was significantly higher in the flag leaves of all three wheat varieties treated with Zn-EDTA compared to control and leaves treated with Zn-sulfate. Both forms of Zn increased malondialdehyde level and total phenolics content in varieties Srpanjka and Divana. Total glutathione content was not affected after the Zn treatment. Zn-sulfate increased the activities of glutathione reductase (GR) and guaiacol peroxidase (GPOD) in both Srpanjka and Divana, while glutathione S-transferase (GST) was only induced in var. Srpanjka. Chelate form of Zn increased the activities of GST and GPOD in both Simonida and Divana. Catalase activity was shown to be less sensitive to Zn treatment and was only induced in var. Srpanjka treated with Zn-EDTA where GPOD activity was not induced. Concentrations of Zn used for agronomic biofortification can induce oxidative stress in wheat leaves. The antioxidative status of wheat leaves could be a good indicator of Zn tolerance, whereas wheat genotype and chemical form of Zn are the most critical factors influencing Zn toxicity.

Astaxanthin attenuates hepatic steatosis in high-fat diet-fed rats by suppressing microRNA-21 via transactivation of nuclear factor erythroid 2-related factor 2.

This study examined whether astaxanthin (ASX) could alleviate hepatic steatosis in rats fed a high-fat diet (HFD) by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/miR-21 axis. Rats (n = 8/group) were fed either a standard diet (3.8kcal/g; 10% fat) or HFD (4.6kcal/g; 40% fat) and treated orally with either the vehicle or ASX (6mg/kg) daily for 8days. Another group was fed HFD and treated with ASX and brusatol (an Nrf2 inhibitor) (2mg/kg/twice per week/i.p.). ASX prevented the gain in body and liver weights and attenuated hepatic lipid accumulation in HFD-fed rats. In the control and HFD-fed rats, ASX did not affect food intake, serum free fatty acid (FFA) content, and glucose and insulin levels and tolerance. However, serum triglyceride (TG), cholesterol, and low-density lipoprotein-cholesterol levels; hepatic levels of TGs and FFAs; and hepatic levels of Srebp1, Srebp2, HMGCR, and fatty acid synthase mRNAs and miR-21 were reduced and the mRNA levels of Pparα were significantly increased in both the groups. These effects were associated with a reduction in the hepatic levels of reactive oxygen species, malondialdehyde, tumor necrosis factor-α, and interlukin-6 as well as an increase in superoxide dismutase levels, total glutathione content, and nuclear levels and activity of Nrf2. miR-21 levels were strongly correlated with the nuclear activity of Nrf2. Brusatol completely reversed the effects of ASX. In conclusion, ASX prevents hepatic steatosis mainly by transactivating Nrf2 and is associated with the suppression of miR-21 and Srebp1/2 and upregulation of Pparα expression.

Antioxidant Effect of Saccharomyces cerevisiae Enriched with Selenium Against Pseudomonas aeruginosa Infection

Background: The reaction of immune cells to the introduction of pathogens into the body is an increase in reactive oxygen species, which leads to the induction of oxidative stress. Reducing the level of oxidative stress through the use of antioxidants strengthens the immune system. Objectives: This study aimed to investigate the antioxidant effects of Saccharomyces cerevisiae and selenium-enriched S. cerevisiae against the oxidative stress induced by Pseudomonas aeruginosa in rats. Methods: A total of 36 rats were randomly divided into six groups, including control (A), S. cerevisiae (B), S. cerevisiae enriched with selenium (C), P. aeruginosa infection treated with S. cerevisiae (D), P. aeruginosa infection treated with S. cerevisiae enriched with selenium (E), and P. aeruginosa infection (F). At the end of the treatment period, the blood samples were collected to evaluate hematological parameters, total antioxidant capacity, glutathione concentration, and glutathione peroxidase activity. Results: The concentration and activity of antioxidant agents in group F were significantly decreased compared to those of the control group; however, in groups D and E, the levels of the aforementioned factors showed a significant increase compared to those of the infected group. The number of white blood cells in group F showed a significant increase, compared to that of the control group. In other groups, the observed differences in antioxidant factors and blood parameters were not significant, compared to those reported for the control group. Conclusions: The results showed that the induction of oxidative stress by P. aeruginosa was partially reduced by treatment with yeast and selenium-enriched yeast. Further studies are essential to confirm the aforementioned results.

Nanoplastics-induced oxidative stress, antioxidant defense, and physiological response in exposed Wistar albino rats.

Nowadays, plastic pollution and in particular nano(micro)plastics is considered as an issue of global concern in environmental samples. The present work was conducted to clarify the oxidative stress of polystyrene nanoplastics (PS-NPs) exposure and physiological response of male Wistar rats. Animals were treated orally with PS-NPs at four doses (1, 3, 6, and10 mg/kg-day) for 5 weeks. Results demonstrated the accumulation of PS-NPs through whole body scanning and also a dose-dependent increase in the production of reactive oxygen species (ROS). Alterations in antioxidant responses including serum levels of catalase (CAT) and total glutathione content were noticed, but not superoxide dismutase (SOD), pointing towards the perturbation of redox state induced by exposure conditions. Biochemical parameters viz. glucose, cortisol, lipase, lactate, lactate dehydrogenase (LDH), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), triglycerides, and urea showed a significant increase, while total protein, albumin, and globulin levels showed an appreciable decline. The pattern of associations noticed with AChE activity and biochemical responses in our study suggests the possibility that a neurobehavioral effect or dysfunctions in energy metabolism may be the potential modes of action, possibly through stress response as well as liver function. Perturbations of creatinine and uric acid levels are indeed plausible biological explanations for the association with kidney dysfunction. Although we provided a new scientific clue for exploring the biological consequences of NPs which might induce effects such as oxidative stress relating to the induction of antioxidant enzymes, the results warrant additional research with a larger sample size.

Toxicity of boron and vanadium nanoparticles on Danio rerio embryos - Phenotypical, biochemical, and behavioral alterations.

Engineered nanoparticles (NPs) are emerging contaminants of concern and it is important to understand their environmental behavior and ecological risks to exposed organisms. Despite their ubiquitous presence in the environment, there is little information about the hazards of certain NPs, such as boron (BNPs) and vanadium (VNPs). The aim of the present research was to investigate the effects of commercial BNPs and VNPs (80 to 100 nm) to zebrafish embryos, at different levels of biological organization. A range of nominal concentrations for both NPs (0, 0.01, 0.1, 1, and 10mg/L) was tested. Due to the presence of triton X-100 in the NPs' stock dispersions, an additional control group was included (0.001% triton X-100). Survival, hatching, and malformations of embryos were assessed for 96 hours (h) exposure. Locomotor behavior was evaluated at 120 h. Furthermore, embryos were exposed to 0, 1, and 10 mg/L of NPs to evaluate a set of biomarker responses after 96 h: cholinesterase (ChE) and glutathione S-transferase (GST) activities, total glutathione (TG) and energy budgets levels. VNPs induced malformations (10 mg/L), hyperactivity (10 mg/L), erratic swimming (0.01 mg/L), altered swimming pattern (>0.01 mg/L), delayed hatching (10 mg/L) and altered biochemical responses involved in antioxidant defense (GST and TG at >1 mg/L), neurotransmission (ChE at 10 mg/L) and energy metabolism (lipids at >1 mg/L and carbohydrates at 10 mg/L). BNPs caused malformations (10 mg/L), affected swimming pattern (>0.01 mg/L), induced erratic swimming (10 mg/L) and decreased TG content and GST activity (>1 mg/L). At the same concentrations, VNPs affected a greater number of endpoints than BNPs, demonstrating a greater toxicity to zebrafish embryos. The present study shows that BNPs and VNPs may affect aquatic organisms, albeit at relatively great non-environmentally relevant concentrations, reinforcing the importance of the risk assessment of different NPs.

Pretreatment of seeds with hydrogen peroxide improves deep-sowing tolerance of wheat seedlings

Drought is a prevalent natural factor limiting crop production in arid regions across the world. To overcome this limitation, seeds are sown much deeper to boost germination by soil moisture produced by underground water. Seed pretreatment can effectively induce deep-sowing tolerance in plants. In the present study, we evaluated whether H2O2 pretreatment of seeds can initiate metabolic changes and lead to improved deep-sowing tolerance in wheat. Pretreatment with 0.05 μM H2O2 promoted first internode elongation by 13% in the deep-sowing tolerant wheat cultivar “Tir” and by 32% in the sensitive cultivar “Kıraç-66” under deep-sowing conditions, whereas internode elongation was inhibited by diphenyleneiodonium chloride. In contrast to Tir seedlings, H2O2 levels in the first internode of Kıraç-66 seedlings increased under deep-sowing condition in the H2O2-treated group compared to controls. Moreover, these seedlings had significantly lower catalase (CAT), peroxidase (POX), and ascorbate peroxidase (APX) activities but higher NADPH oxidase (NOX) and superoxide dismutase (SOD) activities under the same conditions, which consequently induced greater H2O2 accumulation. Contrary to Tir, both total glutathione and glutathione S-transferase (GST) activity decreased in Kıraç-66 after deep-sowing at 10 cm. However, H2O2 treatment increased the total glutathione amounts and the activities of glutathione-related enzymes (except GST and GPX) in the first internode of Kıraç-66. Taken together, these data support that H2O2 acts as a signaling molecule in the activation of antioxidant enzymes (specifically NOX, SOD, and CAT), regulation of both glutathione-related enzymes and total glutathione content, and upregulation of the cell wall-loosening protein gene TaEXPB23.

Carcinogen sodium arsenite disrupts antioxidant and redox homeostasis in Drosophila melanogaster.

The inadvertent exposure to environmental contaminants has been reported to induce cancer in different animal models. Here, we investigated the toxicity of Sodium Arsenite (SA), a Class I Carcinogen in Drosophila melanogaster. Harwich fly strain (1-3days old) of both sexes were orally exposed to SA (0, 0.0312, 0.0625 and 0.125mM) for 14days for survival study. Thereafter, 5days exposure period was selected to assess the toxic effects of SA on oxidative stress and antioxidant markers. The results indicated that SA induced significant reduction in survival and emergence rate of flies. Furthermore, SA significantly increased Nitric Oxide (NO, nitrite and nitrate) and Hydrogen Peroxide (H2O2) levels in flies compared with control (p<0.05). In addition, SA inhibited catalase and glutathione-S-transferase (GST) activities, and depleted total thiol and glutathione (GSH) contents. Moreover, acetylcholinesterase activity significantly increased in flies treated with SA when compared with control. Sodium arsenite-induced reduction in survival and emergence rates of flies occurred via the disruption of oxidative stress-antioxidant homeostasis in D.melanogaster.

Ruthenium(II) and Platinum(II) Complexes with Biologically Active Aminoflavone Ligands Exhibit In Vitro Anticancer Activity.

Continuing our studies on the mechanisms underlying the cytotoxicity of potential drugs, we have described several aspects of the in vitro anticancer activity of ruthenium(II) and platinum(II) complexes with bioactive, synthetic aminoflavone ligands. We examined the mechanism of proapoptotic activity of cis-dichlorobis(3-imino-2-methoxyflavanone)ruthenium(II), cis-dichlorobis(3-imino-2-ethoxyflavanone)ruthenium(II), and trans-dichlorobis(3-aminoflavone)platinum(II). Cisplatin was used as a reference compound. The cytotoxicity was investigated by MTT assay. The mechanism of proapoptotic activity of the tested compounds was investigated by evaluation of caspase-8 activity, cytometric analysis of annexin-V positive cells, and mitochondrial potential loss measurement. The results showed that ruthenium compounds break partially or completely the cisplatin resistance by activating the caspase 8-dependent apoptosis pathway and loss of mitochondrial membrane potential. Platinum compounds also have a cytostatic effect, but their action requires more exposure time. Potential mechanisms underlying drug resistance in the two pairs of cancer cell lines were investigated: total glutathione content, P-glycoprotein activity, and differences in the activity of DNA repair induced by nucleotide excision. Results showed that cisplatin-resistant cells have elevated glutathione levels relative to sensitive cells. Moreover, they indicated the mechanisms enabling cells to avoid apoptosis caused by DNA damage. Pg-P activity has no effect on the development of cisplatin resistance in the cell lines described.

Effects of postharvest cysteine treatment on sensory quality and contents of bioactive compounds in goji fruit

Effects of cysteine (Cys) treatments (0, 0.01%, 0.05% and 0.10%) on sensory quality and bioactive compounds in goji fruit stored at 4 °C and 90% RH for 10 d were investigated. Results indicated that 0.05% Cys treatment significantly reduced decay ratio and weight loss, and maintained total soluble solid content in goji fruit. Furthermore, 0.05% Cys treatment increased the contents of total phenolic, ascorbic acid and total glutathione, and the ratio of glutathione/oxidized glutathione, resulting in the higher antioxidant capacity. Determination of five free amino acids showed that 0.05% Cys treatment increased the Pro and Tau contents, while had no significant effect on the Cys, Glu and GABA contents. The increase in Tau content might be due to the up-regulation of two key genes involved in the Tau synthesis including CDO and CSAD. These findings suggested that Cys treatment could improve the storage quality in goji fruit.

Lemna minor L. (Su mercimeği)'de Everzol Lacivert ED’ye Dirençte Salisilik Asitin Rolü

The dyes used in the production of the textile industry are toxic substances that are resistant to biological treatment. Most of them have highly complex polymer structures. Salicylic acid (SA) is an important hormone produced by plants that provides tolerance to many biotic and abiotic stress factors. Duckweed (L. minor L.) are free floating plants. These plants have been used in laboratory toxicological studies by many researchers for reasons such as their high adaptability to aquatic environments, their small biomass and their high ability to accumulate contaminants. The aim of this study was to evaluate some biochemical changes in duckweed (L. minor L.) of 75 ppm, 150 ppm and 300 ppm Everzol Navy ED (ENED) reactive dyestuff and 0.5 mM SA and ENED application. Total chlorophyll and carotenoid contents were found higher at 0.5 mM SA and 300 ppm dye applied groups on day 7. Peroxidase (POD), ascorbate peroxidase (APX) and Glutathione S-transferase (GST) activities and total glutathione (GSH) content were increased at 0.5 mM SA with ENED application groups. (Superoxide dismutase) SOD and Catalase (CAT) activity increased on days 1, 4 and 7 in both treatment groups. GR activity decreased in dye applied groups and 0.5 mM SA with dye applied groups on day 7. MDA content decreased on day 7 with 300 ppm dye application and 0.5 mM SA and 300 ppm dye application.

Effects of germination time on the structural, physicochemical and functional properties of brown rice

SummaryGerminated brown rice (GBR) is a gluten‐free food raw material. Its tissue structure, physicochemical properties and functional properties depend on the germination time. In this study, rapid viscosity analyses, differential scanning calorimetry and X‐ray diffraction et al were used to analyse the structural, physicochemical and functional changes in brown rice (BR) during germination. Gamma‐aminobutyric acid (GABA), total phenolic compound, glutathione (GSH) and amino acid contents increased during germination. GBR exhibited the highest GSH (22.70 mg per 100 g) and amino acid (8.02 mg per 100 g) contents at 24 h and the highest GABA content (253.35 mg per 100 g) at 36 h. Furthermore, BR germinated for 36 h showed greater enthalpy (ΔH) than ungerminated BR. Although GBR showed less crystallinity than ungerminated BR, germination did not change the crystalline structure type of starch (A‐type). These results inform choices of the appropriate applications of GBR to promote its utilisation in the food industry.

The Function of the Hypothalamic-Pituitary-Adrenal Axis During Experimental Autoimmune Encephalomyelitis: Involvement of Oxidative Stress Mediators.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease with an unknown origin. Previous studies showed the involvement of the hypothalamic–pituitary–adrenal (HPA) axis to susceptibility to autoimmune diseases, including MS, and its best-characterized animal model, experimental autoimmune encephalomyelitis (EAE). During MS/EAE, innate immune cells are activated and release cytokines and other inflammatory mediators, leading to a vicious cycle of inflammation. In response to inflammation, the activated HPA axis modulates immune responses via glucocorticoid activity. Because the mechanisms involving oxidative stress to the HPA axis are relatively unrevealed, in this study, we investigate the inflammatory and oxidative stress status of HPA axis during EAE. Our results reveal an upregulation of Pomc gene expression, followed by POMC and ACTH protein increase at the peak of the EAE in the pituitary. Also, prostaglandins are well-known contributors of HPA axis activation, which increases during EAE at the periphery. The upregulated Tnf expression in the pituitary during the peak of EAE occurred. This leads to the activation of oxidative pathways, followed by upregulation of inducible NO synthase expression. The reactive oxidant/nitrosative species (ROS/RNS), such as superoxide anion and NO, increase their levels at the onset and peak of the disease in the pituitary and adrenal glands, returning to control levels at the end of EAE. The corticotrophs in the pituitary increased in number and volume at the peak of EAE that coincides with high lipid peroxidation levels. The expression of MC2R in the adrenal glands increases at the peak of EAE, where strong induction of superoxide anion and malondialdehyde (MDA), reduced total glutathione (GSH) content, and catalase activity occurred at the peak and end of EAE compared with controls. The results obtained from this study may help in understanding the mechanisms and possible pharmacological modulation in MS and demonstrate an effect of oxidative stress exposure in the HPA activation during the course of EAE.

Effect of Benzophenone-3 to Acetylcholinesterase and Antioxidant System in Zebrafish (Danio rerio) Embryos.

Benzophenone-3 (BP-3) is one of the most used UV filters. The present study aimed to evaluate the toxic effects of BP-3 during embryo stages of zebrafish four hours post-fertilization (4hpf). Embryos were exposed to 0, 1, and 10µg L-1 of BP-3 for 72h. We investigated biochemical and molecular biomarkers of neurotoxicity (AChE) and the antioxidant system (gene expression of catalase, CAT, superoxide dismutase, SOD, glutathione peroxidase, GPX, the concentration of total glutathione, GSH, and lipid hydroperoxides, LPO). Results indicated that the acute exposure to BP-3 in zebrafish embryos did not show significant differences in survival, hatching rate, or antioxidant system biomarkers. In contrast, there were significant differences associated with AChE gene expression and activity.

Pila virens as sentinel of silica nanoparticles toxicity induced oxidative stress

The aquatic ecosystem is under threat due to the continuous inlet of various emerging contaminants affecting the inhabiting organisms. The Silica nanoparticles (SiNPs) are among the most abundantly produced nanoparticles globally posing a threat to the aquatic organisms because of their entry into aquatic ecosystem through various point and nonpoint sources. In this work, we report the toxicological impacts of SiNPs on fresh water snail Pila virens (P.virens) as a biomonitor. The acute toxicity of SiNPs on P. virens was performed in a 96 h static renewal tests. The median lethal concentration of SiNPs for 96 h on P. virens is 366.92 µg/L. The P. virens were exposed to 165 µg/L for 24 and 48 h respectively shown a significant increase in lipid peroxidation, protein carbonyl, superoxide dismutase and reduction in total glutathione content in comparison to their controls. The fresh water edible snail P. virens serve as model organisms for other engineered nanomaterials toxicity.

α-Chaconine Affects the Apoptosis, Mechanical Barrier Function, and Antioxidant Ability of Mouse Small Intestinal Epithelial Cells.

α-Chaconine is the most abundant glycoalkaloid in potato and toxic to the animal digestive system, but the mechanisms underlying the toxicity are unclear. In this study, mouse small intestinal epithelial cells were incubated with α-chaconine at 0, 0.4, and 0.8 μg/mL for 24, 48, and 72 h to examine apoptosis, mechanical barrier function, and antioxidant ability of the cells using a cell metabolic activity assay, flow cytometry, Western blot, immunofluorescence, and fluorescence quantitative PCR. The results showed that α-chaconine significantly decreased cell proliferation rate, increased apoptosis rate, decreased transepithelial electrical resistance (TEER) value, and increased alkaline phosphatase (AKP) and lactate dehydrogenase (LDH) activities, and there were interactions between α-chaconine concentration and incubation time. α-Chaconine significantly reduced the relative and mRNA expressions of genes coding tight junction proteins zonula occludens-1 (ZO-1) and occludin, increased malondialdehyde (MDA) content, decreased total glutathione (T-GSH) content, reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and γ-glutamylcysteine synthetase (γ-GCS) and the mRNA expressions of SOD, CAT, GSH-Px, and γ-GCS genes. In conclusion, α-chaconine disrupts the cell cycle, destroys the mechanical barrier and permeability of mucosal epithelium, inhibits cell proliferation, and accelerates cell apoptosis.

Effects of p-Cresol on Oxidative Stress, Glutathione Depletion, and Necrosis in HepaRG Cells: Comparisons to Other Uremic Toxins and the Role of p-Cresol Glucuronide Formation.

The toxicological effects of p-cresol have primarily been attributed to its metabolism products; however, very little human data are available in the key organ (i.e., liver) responsible for the generation of these metabolites. Experiments were conducted in HepaRG cells utilizing the following markers of cellular toxicity: 2′-7′-dichlorofluorescein (DCF; oxidative stress) formation, total cellular glutathione (GSH) concentration, and lactate dehydrogenase (LDH; cellular necrosis) release. Concentrations of p-cresol, p-cresol sulfate, and p-cresol glucuronide were determined using validated assays. p-Cresol exposure resulted in concentration- and time-dependent changes in DCF (EC50 = 0.64 ± 0.37 mM at 24 h of exposure) formation, GSH (EC50 = 1.00 ± 0.07 mM) concentration, and LDH (EC50 = 0.85 ± 0.14 mM) release at toxicologically relevant conditions. p-Cresol was also relatively more toxic than 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, indole-3-acetic acid, indoxyl sulfate, kynurenic acid, and hippuric acid on all markers. Although the exogenous administration of p-cresol sulfate and p-cresol glucuronide generated high intracellular concentrations of these metabolites, both metabolites were less toxic compared to p-cresol at equal-molar conditions. Moreover, p-cresol glucuronide was the predominant metabolite generated in situ from p-cresol exposure. Selective attenuation of glucuronidation (without affecting p-cresol sulfate formation, while increasing p-cresol accumulation) using independent chemical inhibitors (i.e., 0.75 mM l-borneol, 75 µM amentoflavone, or 100 µM diclofenac) consistently resulted in further increases in LDH release associated with p-cresol exposure (by 28.3 ± 5.3%, 30.0 ± 8.2% or 27.3 ± 6.8%, respectively, compared to p-cresol treatment). These novel data indicated that p-cresol was a relatively potent toxicant, and that glucuronidation was unlikely to be associated with the manifestation of its toxic effects in HepaRG cells.