Decrease In GSH Research Articles

The deleterious effect of xylene-induced ear edema in rats: Protective role of dexketoprofen trometamol transdermal invasomes via inhibiting the oxidative stress/NF-κB/COX-2 pathway

Pain and inflammation could have a negative impact on a patient's quality of life and performance, causing them to sleep less. Dexketoprofen trometamol (DKT) is a water-soluble, nonselective NSAIDs. Because DKT is quickly eliminated in the urine after oral delivery, its efficacy is limited and must be taken repeatedly throughout the day. The main ambition of this work is to develop and characterize the potential of invasomes to enhance the transdermal transport of DKT to achieve efficient anti-inflammatory and pain management. The optimum formulation (C1) showed the least %RE (53.29 ± 2.68 %), the highest %EE (86.51 ± 1.05 %), and spherical nanosized vesicles (211.9 ± 0.57 nm) with (PDI) of 0.353 ± 0.01 and (ZP) of −19.15 ± 2.45 mV. DKT flux and deposition in stratum corneum, epidermal, and dermal skin layers were significantly augmented by 2.6 and 3.51 folds, respectively, from the optimum invasomal gel formulation (C1-G) compared to DKT conventional gel (DKT-G). The anti-inflammatory activity of C1-G was evaluated using a model of xylene-induced ear edema in rats. Xylene exposure upregulated the ear expression of COX-2 level and MPO activity. Xylene also significantly increased the ear NF-κB p65, TNF-α, IL-Iβ, and MDA levels. Furthermore, xylene induced oxidative stress, as evidenced by a significant decrease in ear GSH and serum TAC levels. These impacts were drastically improved by applying C1-G compared to rats that received DKT-G and plain invasomal gel formulation (plain C1-G). The histopathological findings imparted substantiation to the biochemical and molecular investigations. Thereby, C1-G could be a promising transdermal drug delivery system to improve the anti-inflammatory and pain management of DKT.

Anti oxidative activities of aqueous and ethanolic extracts of stem barks from trichilia emetica in albinos rats

: In chronic diseases in general and in diabetes mellitus and hypertension in particular, there is an important imbalance between antioxidant defenses and the production of free radicals due to reactive oxygen species, thus leading to an increase in oxidant stress markers. Therefore, this study was designed to evaluate the antioxydative and protective effects of aqueous and ethanolic extracts of trichilia emetica stem bark in albinos rats with alloxan-induced diabetes or adrenaline-induced hypertensive.: Two different batches of albinos rats were used distinctly and including a control one of 3 rats for each batch so a test group of 21 rats. Diabetes was induced by injecting Alloxane® intraperitoneally for 7 days. Hypertension was induced by injecting Adrenaline® intraperitoneally for eight days and we used visitech BP 2000 tools to measure arterial pressure. The aqueous and ethanolic extracts of Trichilia emetica were prepared and the obtained mixture was homogenized using a magnetic stirrer for 24 hours. Rats received the above-mentioned extracts orally at doses of 100 and 200 mg/kg bw for 6 days.: Aorta and heart activities of catalase were significantly increased. This same trend was observed with superoxide dismutase activity together with increasing AChE catalytic activity in vessels. Treatment of rats for seven days with extracts of Trichilia emetic and nifedipineproduced a significant decrease of antioxidative markers activities of catalase and SOD for aqueous and ethanolic extracts as well. This action was slightly above nifedipineone administrated at 10 and 20 mg/kg bw. For rats treated with Trichilia emetica or with diastabolwe registered a significant decrease of MDA and GSH concentration.Our results showed that the extracts have the potential to reduce the rate of reactive oxygen species and free radicals in rats with alloxane-induced diabetes or adrenaline-induced hypertensive. However, further large studies are needed to investigate the specific action and particularity of Trichilia emetica that could justify these activities.

Epigallocatechin Gallate Attenuates Gentamicin-Induced Nephrotoxicity by Suppressing Apoptosis and Ferroptosis

Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.

Study the antioxidant effect of coconut oil in rabbits treated with sodium nitrate

The present study was conducted to explore the effect of different concentrations of coconut oil as an antioxidant with rate of (1.5, 2 ,2.5ml/kg) of body weight given orally and measure Hematological parameters (white blood cells,PCV , Hb and platelets) and biochemical parameters (cholesterol and its different kinds (Total cholesterol, HDL, LDL, VLDL), triglycerides) and liver enzymes (Superoxide dismutase , Glutathione) in rabbits that demonstrated sodium nitrate as oxidative material use concentration (75 mg / kg), and compared to all results with control group . The results showed a decrease in triglycerides, LDL , SOD and GSH , increase HDL cholesterol levels and a raise in the number of white blood cells, platelets and Hb level this results belong to increase the number of free radicals as a result of oxidative stress caused by the use of sodium nitrate.

Hepatoprotective effect of a polyherbal formulation (Aab-e-Murawaqain) against CCl4 induced liver toxicity in Wistar albino rat model by suppressing proinflammatory cytokines

This study assessed the hepatoprotective action of Aab-e-Murawaqain in Wistar albino rats by inducing liver injury with carbon tetra chloride (CCl 4 ) (2 mL/kg; sc). Aqueous extracts of Solanum nigrum (Makoy) and Cichorium intybus (Kashni) were used to prepare the Aab-e-Murawaqain polyherbal formulation. Silymarin (25 mg/kg), a well-known liver protective medicine, was treated as the reference control group. Biochemical indicators, such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), and total bilirubin, were used to assess the curative potential. Other common biomarkers, such as thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT), were also estimated. Animals treated with CCl 4 exhibited significantly enhanced in SGOT, SGPT, ALP, bilirubin, and TBARS level, reflecting hepatic damage. The formulation considerably minimised the increase serum enzyme levels, indicating the improvement in liver cellular injury. CCl 4 induced significant decrease in GSH, SOD, and CAT levels. Pretreatment of the rats with the formulation led to an increase in hepatic GSH, SOD, CAT, protein, and albumin levels. Moreover, CCl 4 administration led to an increase in TNF-α, IL-6, and IL-10 levels, which decreased with polyherbal formulation treatment. The results were validated through histological evolutions, which revealed minimum fatty variations and a noticeable regenerative effect in the livers after treatment with the formulation. The results confirmed that Aab-e-Murawaqain can provide a substantial activity in the management of CCl 4 -induced hepatotoxicity.

The Abnormal Proliferation of Hepatocytes is Associated with MC-LR and C-Terminal Truncated HBX Synergistic Disturbance of the Redox Balance.

Microcystin-LR (MC-LR) and hepatitis B virus (HBV) are associated with hepatocellular carcinoma (HCC). However, the concentrations of MC-LR in drinking water and the synergistic effect of MC-LR and HBV on hepatocellular carcinogenesis through their disturbance of redox balance have not been fully elucidated. We measured the MC-LR concentrations in 168 drinking water samples of areas with a high incidence of HCC. The relationships between MC-LR and both redox status and liver diseases in 177 local residents were analyzed. The hepatoma cell line HepG2 transfected with C-terminal truncated hepatitis B virus X gene (Ct-HBX) were treated with MC-LR. Reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) were measured. Cell proliferation, migration, invasion, and apoptosis were assessed with cell activity assays, scratch and transwell assays, and flow cytometry, respectively. The mRNA and protein expression-related redox status genes were analyzed with qPCR and Western blotting. The average concentration of MC-LR in well water, river water and reservoir water were 57.55 ng/L, 76.74 ng/L and 132.86 ng/L respectively, and the differences were statistically significant (P < 0.05). The MC-LR levels in drinking water were correlated with liver health status, including hepatitis, clonorchiasis, glutamic pyruvic transaminase abnormalities and hepatitis B surface antigen carriage (all P values < 0.05). The serum MDA increased in subjects who drank reservoir water and were infected with HBV (P < 0.05). In the cell experiment, ROS increased when Ct-HBX-transfected HepG2 cells were treated with MC-LR, followed by a decrease in SOD and GSH and an increase in MDA. MC-LR combined with Ct-HBX promoted the proliferation, migration and invasion of HepG2 cells, upregulated the mRNA and protein expression of MAOA gene, and downregulated UCP2 and GPX1 genes. MC-LR and HBV may synergistically affect redox status and play an important role in hepatocarcinoma genesis.

Drought-Induced Xylem Sulfate Activates the ABA-Mediated Regulation of Sulfate Assimilation and Glutathione Redox in Brassica napus Leaves.

Drought intensity modifies the assimilatory pathway of glutathione (GSH) synthesis. Abscisic acid (ABA) is a representative signaling hormone involved in regulating plant stress responses. This study aimed to investigate an interactive regulation of sulfate and/or ABA in GSH metabolism and redox. The drought-responsive alterations in sulfate assimilation and GSH-based redox reactions were assessed relative to ABA responses on the time-course of drought intensity. Drought-responsive H2O2 concentrations were divided into two distinct phases-an initial 4 days of no change (Ψw ≥ -0.49 MPa) and a phase of higher accumulation during the late phase of the drought (days 10-14; Ψw ≤ -1.34 MPa). During the early phase of the drought, GSH/GSSG redox state turned to the slightly reduced state with a transient increase in GSH, resulting from a strong activation of H2O2 scavenging enzymes, ascorbate peroxidase (APOX) and glutathione reductase (GR). The late phase of the drought was characterized by a decrease in GSH due to cysteine accumulation, shifting GSH- and NADPH-based redox states to higher oxidization, increasing sulfate and ABA in xylem, and causing ABA accumulation in leaves. Regression analysis revealed that sulfate in xylem sap was positively correlated with H2O2 concentrations and ABA was closely related to decreases in the GSH pool and the oxidation of GSH catalyzed by glutathione peroxidase (GPOX). These results indicate that drought-induced oxidation proceeds through the suppression of GSH synthesis and further GSH oxidation in a sulfate-activated ABA-dependent manner.

Effects of bisphenol A on antioxidation and nitrogen assimilation of maize seedlings roots

Bisphenol A (BPA) is becoming a potential environmental toxicity factor. However, BPA's effect and function mechanism on maize roots remain unknown. Here, we investigated characters of root growth of maize seedlings exposed to BPA for 8 d and without BPA for 3 d, and a series of indicators on reactive oxygen homeostasis and nitrogen assimilation were measured. High-dose BPA(15 and 50 mg·L−1) suppressed the root growth and caused increased contents of O2ˑ-, H2O2 and MDA in maize seedling roots. The disturbed ROS homeostasis resulted from the change of antioxidant enzymes, including the increase of APX, GPX, and CAT, and decrease of SOD and POD, and a decrease of antioxidant substance GSH. Meanwhile, High-dose BPA caused a decrease in the soluble protein content, nitrate reductase (NR), glutamate dehydrogenase (GDH), and glutamine oxoglutarate aminotransferase (GOGAT) under the BPA processing phase and recovery period. The low-dose BPA（1.5 and 5 mg·L−1）significantly promoted root growth of maize seedlings and maintained the ROS homeostasis through antioxidant enzyme APX and GPX eliminating redundant ROS. Our results showed that BPA could cause a dual effect on the root growth of maize seedlings, that is, promotion of low-dose and inhibition of high-dose, through ROS homeostasis and nitrogen assimilation in Zea mays.

GSK872 and necrostatin-1 protect retinal ganglion cells against necroptosis through inhibition of RIP1/RIP3/MLKL pathway in glutamate-induced retinal excitotoxic model of glaucoma

BackgroundGlaucoma, the major cause of irreversible blindness worldwide, is characterized by progressive degeneration of retinal ganglion cells (RGCs). Current treatments for glaucoma only slow or partially prevent the disease progression, failing to prevent RGCs death and visual field defects completely. Glutamate excitotoxicity via N-methyl-d-aspartic acid (NMDA) receptors plays a vital role in RGCs death in glaucoma, which is often accompanied by oxidative stress and NLRP3 inflammasome activation. However, the exact mechanisms remain unclear.MethodsThe glutamate-induced R28 cell excitotoxicity model and NMDA-induced mouse glaucoma model were established in this study. Cell counting kit-8, Hoechst 33342/PI dual staining and lactate dehydrogenase release assay were performed to evaluate cell viability. Annexin V-FITC/PI double staining was used to detect apoptosis and necrosis rate. Reactive oxygen species (ROS) and glutathione (GSH) were used to detect oxidative stress in R28 cells. Levels of proinflammatory cytokines were measured by qRT-PCR. Transmission electron microscopy (TEM) was used to detect necroptotic morphological changes in RGCs. Retinal RGCs numbers were detected by immunofluorescence. Hematoxylin and eosin staining was used to detect retinal morphological changes. The expression levels of RIP1, RIP3, MLKL and NLRP3 inflammasome-related proteins were measured by immunofluorescence and western blotting.ResultsWe found that glutamate excitotoxicity induced necroptosis in RGCs through activation of the RIP1/RIP3/MLKL pathway in vivo and in vitro. Administration of the RIP3 inhibitor GSK872 and RIP1 inhibitor necrostatin-1 (Nec-1) prevented glutamate-induced RGCs loss, retinal damage, neuroinflammation, overproduction of ROS and a decrease in GSH. Furthermore, after suppression of the RIP1/RIP3/MLKL pathway by GSK872 and Nec-1, glutamate-induced upregulation of key proteins involved in NLRP3 inflammasome activation, including NLRP3, pro-caspase-1, cleaved-caspase-1, and interleukin-1β (IL-1β), was markedly inhibited.ConclusionsOur findings suggest that the RIP1/RIP3/MLKL pathway mediates necroptosis of RGCs and regulates NLRP3 inflammasome activation induced by glutamate excitotoxicity. Moreover, GSK872 and Nec-1 can protect RGCs from necroptosis and suppress NLRP3 inflammasome activation through inhibition of RIP1/RIP3/MLKL pathway, conferring a novel neuroprotective treatment for glaucoma.

Hepatoprotective effects of carvedilol and crocin against leflunomide-induced liver injury

Leflunomide-induced liver injury has been an important problem since its approval. Although, severe cases of leflunomide-induced liver injury leading to hospitalization are rare, the risk is higher with concurrent liver disease or use of other hepatotoxic drugs.The current study was conducted to investigate the potential protective effects of carvedilol and crocin alone and in combination against leflunomide-induced hepatic injury and to clarify the possible mechanism(s) through which carvedilol and crocin may elicit their effects.Fifty male albino mice were allocated into five groups: normal control group, leflunomide group, carvedilol group, crocin group, and combination group. These groups were given vehicle, leflunomide, leflunomide plus carvedilol, leflunomide plus crocin, and leflunomide plus combination of carvedilol and crocin, respectively. The study was conducted for 8 weeks, and different parameters were assessed.The results demonstrated that leflunomide significantly increased the serum levels of AST, ALT, ALP, hepatic MDA, nitrite, mTOR gene, PI3K gene, TGF-β, and the pathological changes alongside with the significant decrease of serum albumin, total protein, hepatic catalase, and GSH. While the coadministration of carvedilol, crocin and their combination with leflunomide significantly decreased the serum levels of AST, ALT, ALP, hepatic MDA, mTOR gene, PI3K gene, TGF-β, and the pathological changes alongside with the significant elevation of serum albumin, total protein, hepatic catalase, and GSH.This study is suggesting several solutions for Leflunomide-induced hepatotoxicity demonstrated by the protective effect of the antihypertensive drug carvedilol, the natural product crocin, and their combination which was demonstrated to be superior to each drug alone.

CHRONIC THIACLOPRID EXPOSURE IMPAIRS COGNITIVE FUNCTION AND TRIGGERS MITOCHONDRIAL APOPTOSIS PATHWAY IN RAT STRIATUM AND HIPPOCAMPUS: NEUROPREVENTIVE EFFECT OF BITTER APRICOT KERNELS EXTRACT (PRUNUS ARMENIACA L.)

Thiacloprid (THI) is a nicotinic receptor agonist widely used as pesticide in Algeria, however it is susceptible to accumulate in various fruits and vegetables and pouring downstream into food plates and contributes to the development of neurodegenerative diseases. Conversely, several natural compounds are provided with cytoprotective potential and, therefore, are able to act against the harmful effects of toxicants such as pesticides. This study focused on striatum (str) and hippocampus (hipp) mitochondrial toxicity assessment, evaluation of behavioral function and intrinsic apoptosis pathway in rats exposed to THI at low-dose (0.020 mg/kg) for 3 months. In addition, this study examined neuroprotective potential of bitter apricot kernel extract when administered concomitantly with THI at the dose of 50 mg/kg. In current study, assessment of mitochondrial permeability transition pore (mPTP) and swelling, evaluation of mitochondrial redox status, cholinergic function (Ach E) and apoptosis markers (Caspase 9 and 3, Bax and Bcl2, Cytochrome c and cytosolic calcium) were performed in both brain areas, besides behavioral and histopathological examination. The results showed an increase of lipid peroxidation in both of str and hipp with a values of 1,14 ± 0,04 nmol/mg of proteins (pr) and 1,58 ± 0,09 nmol/mg pr. respectively and a significant decrease in GSH (0,09 ± 0,01 mmol/mg pr. in hipp and 0,08±0,01 mmol/mg pr. in str), the results also showed a change in the activity of antioxidants enzymes SOD (16,37±1,09 UI/mg pr. in hipp14,54±1,46 UI/mg pr. in str) , CAT (0,010±0,01 UI/mg pr. in hipp and 0,005±0,004 UI/mg pr. in str), GPx (0,01± 0,001 nmol/mg pr. in both hipp and str) and GST (23,73±1,68 UI/mg pr. in hipp and 17,56± 1,04 UI/mg pr. in str), as well as an abrupt increase in mPTP opening with a value of (0,057±0,005 in str and 0,054±0,005 in hipp) , which leaded to mitochondrial swelling where the level o mitochondrial swelling was (0,016±0,002 in str and 0,106±0,003 in hipp), the swelling was associated also with a high releasing of Cyt-c with a values of (4,48 ± 1,26 µg/ml in str and 5,32 ± 1,08 µg/ml in hipp ) and Ca++( 2,26±0,06 mmol/l in str and 2,32±0,07 mmol/l in hipp) into the cytosol, the results also showed a significant decreasing of Bcl2 (16,4 ± 1,86 ng/mg pr in str and 14,8± 0,82 ng/mg pr in hipp), in the other hand the rates of caspase-9 were (278±14 mAbs/mg pr.) in str and 212 ±24 mAbs/mg pr. in hipp), caspase3 (184± 16mAbs/mg pr.) in str and 250 ±14mAbs/mg pr. in hipp), and BAX (0,926 ng/mg pr in str and 1,189 ng/mg pr in hipp) were increased. The results of this study revealed also a decrease of memorization processes and learning abilities, at the same time a decrease in Ach E activity (14,02± 0,78 nmol/min/mg pr. in str and 22,35± 1,77 nmol/min/mg pr. in hipp) was recorded. Inversely, bitter apricot kernels extract showed higher cytoprotective potential against THI neurotoxicity, since mitochondrial redox homeostasis and membrane integrity were recovered, cognitive impairment and brain tissue damage were also prevented. In conclusion, THI induced mitochondrial disorders, triggered apoptosis signaling pathway and impaired cognitive functions which were prevented by bitter apricot kernels extract when associated with this pesticide.

MiR-2115-3p inhibits ferroptosis by downregulating the expression of glutamic-oxaloacetic transaminase in preeclampsia

IntroductionRecently, ferroptosis has been reported to be closely related to preeclampsia (PE). However, the mechanisms associated with ferroptosis in PE have been poorly studied. MethodsA PE rat model was established via reduced uterine perfusion pressure (RUPP) surgery. A Ferroptosis inhibitor was used to treat the model rats. Blood pressure, urine protein, sFlt-1, GSH, GSH-PX, MDA, total Fe, Fe (II), and Fe (Ⅲ) levels were detected. Placenta morphological changes and fetal survival rate were observed and counted, respectively. miRNA sequencing and bioinformatical analysis were conducted to establish the ferroptosis-related interaction network of miRNAs-mRNAs in PE. After hypoxia treatment, cells were silenced glutamic-oxaloacetic transaminase1 (GOT1) or overexpressed miR-2115-3p/GOT1. Cellular proliferation, invasion, and reactive oxygen species (ROS) were determined. The ferroptosis-related factors levels (ACSL4, TfR1, GPX4, SCL7A11, GSH, GSH-PX, Fe (II), and MDA) were quantified. ResultsIn vivo, ferrostatin-1 attenuated ferroptosis in the PE models, significantly increasing fetal survivability. The miR-2115-3p/GOT1 pathway was screened for possible association with abnormal ferroptosis in PE. miR-2115-3p was discovered to interact with the mRNA of GOT1. Inhibition of GOT1 and overexpression of miR-2115-3p reversed the decrease in cell proliferation capacity, GSH, GSH-PX, and GPX4 levels, and the increase in ROS, ACSL4, TfR1, MDA, total Fe, and Fe (II) levels induced by hypoxia. However, simultaneous overexpression of miR-2115-3p and GOT1 reversed the above results of overexpression of miR-2115-3p. DiscussionmiR-2115-3p might interact with the GOT1 mRNA to downregulate its expression, further inhibiting the hypoxia-promoted ferroptosis in a PE model.

Quantification of reduced and oxidized glutathione in wine by MALDI-TOF MS

Reduced glutathione (GSH) is one of the important antioxidants in the winemaking and aging process and it also regulates the color and flavor of wines. Accurate and rapid quantification of GSH is crucial in wine quality control. In this study, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was demonstrated to quantify GSH and oxidized glutathione (GSSG) of wine in a high-throughput way. Quinoline-5,8-dione was used as a label to react with GSH, and the derivative of GSH, glutamate-cysteine-alanine, acted as the internal standard (IS). The quantitative decrease of GSH and the increase in GSSG were detected with a relative standard deviation of ≤ 5%, after the wines were exposed to air from one to seven days, and the concentration changes of GSH and GSSG were measured by simple dilution. All the results suggested the feasibility and potential of this method for wider applications in the quantification of GSH and GSSG.

HMOX1 silencing prevents doxorubicin-induced cardiomyocyte injury, mitochondrial dysfunction, and ferroptosis by downregulating CTGF.

Doxorubicin is a type of effective antitumor drug but can contribute to cardiomyocyte injuries. We aimed to dissect the mechanism of the HMOX1/CTGF axis in DOX-induced cardiomyocyte injury, mitochondrial dysfunction, and ferroptosis. Bioinformatics analysis was conducted to retrieve differentially expressed genes in a DOX-induced mouse model. Mouse cardiomyocytes, HL-1 cells, were induced with l µM DOX, after which gain- or loss-of-function assays were applied. CCK-8, fluorescent probe assay, flow cytometry, and corresponding kits were employed to detect cell viability, ROS levels, mitochondrial membrane potential and cell apoptosis, and GSH and Fe2+ contents, respectively. qRT-PCR or Western blot assay was adopted to test HMOX1, CTGF, BCL-2, Caspase3, Cleaved-Caspase3, and GPX4 expression. Bioinformatics analysis showed that HMOX1 and CTGF were highly expressed in DOX-induced mice and correlated with each other. Also, HMOX1 and CTGF expression was high in HL-1 cells after DOX treatment, along with an obvious decrease in cell viability and GSH and GPX4 expression, an increase in ROS levels, apoptosis, and Fe2+ contents, and mitochondrial membrane potential dysfunction or loss. HMOX1 or CTGF silencing diminished cell apoptosis, Cleaved-Caspase3 expression, Fe2+ contents, and ROS levels, enhanced cell viability and the expression of GSH, GPX4, and BCL-2, and recovered mitochondrial membrane potential in DOX-induced HL-1 cells. Nevertheless, the effects of HMOX1 silencing on the viability, apoptosis, ferroptosis, and mitochondrial dysfunction of DOX-induced HL-1 cells were counteracted by CTGF overexpression. In conclusion, HMOX1 silencing decreased CTGF expression to alleviate DOX-induced injury, mitochondrial dysfunction, and ferroptosis of mouse cardiomyocytes.

Amelioration of experimental nephrotoxicity due to 5-Flourouracil by Resveratrol in comparison to Vitamin-E

The therapeutic efficacy of Resveratrol (RSV) and Vitamin E were studied against 5-Flourouracil (5-FU) induced nephrotoxicity. 36 male Wistar rats were selected randomly weighing between 150-180 g and are made into 6 groups, each group containing 6 rats. Group 1 was maintained as sham. 5-Flourouracil was administered to groups 2, 5 and 6 intraperitoneally (20 mg/kg body weight) on day 1, 3 and 7. Group 2 was kept as positive control (administered 5-FU intraperitoneally). Groups 3, 5 and 4, 6 were administered vitamin E and resveratrol per orally for 14 days @ 200 mg/kg bwt. At the end of the experiment the blood was withdrawn and serum analyzed for renal biomarkers. For histopathological studies, samples of kidney tissue collected by inducing euthanasia in rats. The sero-biochemical analysis revealed a significant increase in BUN and creatinine values of the rats in group 2. The antioxidant activity was analyzed and the rats in group 2 revealed a significant rise in the values of protein carbonyl, TBARS and significant decrease in GSH. Group 2 also showed an increase in TNF-α and decrease in interleukin-10 concentration. Sections of kidney tissue collected from group 2 showed marked dilation and elongation of tubules, moderate infiltration with inflammatory cells degeneration of bowman’s capsule and tubular congestion. Comparatively, groups undergone treatment showed amelioration in the parameters. Thus, resveratrol and vitamin-E exert protective actions against 5-flourouracil (5-FU) induced nephrotoxicity.

Hepatoprotective Effect of Opuntia robusta Fruit Biocomponents in a Rat Model of Thioacetamide-Induced Liver Fibrosis.

Liver fibrosis is a chronic disease associated with oxidative stress that has a great impact on the population mortality. Due to their antioxidant capacity, we evaluated the protective effect of Opuntia robusta fruit (Or) on liver fibrosis. A nutraceutical characterization of Or was performed and a model of fibrosis was induced with thioacetamide (TAA) in Wistar rats. Aminotransferases, reduced glutathione (GSH) and histopathology were evaluated. Or contained 436.5 ± 57 mg of Betacyanins equivalents/L., 793 mg of catechin equivalents (CAE)/100 g for flavonoids, 1118 mg of gallic acid equivalents (GAE)/100 g for total phenols, 141.14 mg/100 g for vitamin C and 429.9 μg/100 g for vitamin E. The antioxidant capacity of Or was: 2.27 mmol of Trolox® equivalents (TE)/L (DPPH), 62.2 ± 5.0 μmol TE/g (ABTS•+), 80.2 ± 11.7 μmol TE/g (FRAP), 247.9 ± 15.6 µmol TE/g (AAPH) and 15.0% of H2O2 elimination. An increase (p < 0.05) of aminotransferases and a decrease (p < 0.05) of hepatic GSH was observed in the TAA group compared to the control and the concomitant groups. Histopathology showed changes in the normal architecture of the liver treated with TAA compared to the concomitant treatments. Or contains bioactive components with antioxidant capacity, which can reduce fibrotic liver damage.

Microsomal P450-related Electron Transfer Components, Glutathione and Glutathione S-transferase Contribution in Stress Response of Herbicide-treated Wheat to Drought and Waterlogging

The activities of some plant microsomal P450-related electron transfer components (NADPH-cytochrome P450 reductase, CPR and NADH-cytochrome b5 reductase, B5R), glutathione S-transferase (GST) together with the content of reduced (GSH) and oxidized (GSSG) glutathione were determined in wheat (Triticum aestivum L., cv. Sadovo 1) treated with herbicide Serrate® prior to drought or waterlogging. Both stresses, especially drought, increased the content of glutathione and the activities of CPR and B5R during the stress, while GST activity was rather decreased. Herbicide application alone increased substantially most of the parameters, especially at the beginning of the experimental period. Serrate®+drought/waterlogging (S+D/W), amplified the observed alterations (except for GST), which were more significant after drought. The decrease in ratio GSH to GSSG after 4 days of recovery for all treatment groups except Serrate® signifies disrupted buffer capacity in cells. After 4 days of recovery the activities of CPR and B5R dropped below the control, while the glutathione pool and GST activity remained increased in drought and S+D treated plants. Contrariwise, the levels of glutathione, CPR and B5R remained closer to control in waterlogged plants, while S+W kept higher levels of P450-related enzymes. The herbicide application prior to drought or waterlogging did not affect negatively detoxification and oxidative status of wheat plants compared to those subjected to water stress alone.

Duration Dependent Impact of Aspartame and Sacoglottis gabonensis on the Liver of Swiss Mice

Aim: This study aimed at evaluating the duration dependent impact of aspartame and Sacoglottis gabonensis on the liver of male swiss mice.&#x0D; Location and Duration of Study: The study was carried out in the green house of the Department of Animal and Environmental Biology, Rivers State University, Nkpolu-Oroworukwo, Port Harcourt, Nigeria (Coordinates 4o48’14’'N 6o59’12”E). The experiment lasted for Ninety days.&#x0D; Experimental Design: A completely randomized experimental design employing relevant statistical tools for analysis and interpretation.&#x0D; Methodology: Ninety adult male mice were assigned to six groups (A-F) of fifteen mice each. Group A was the negative control and so they were not given any treatment, but only given pellet and clean tap water. Group B was the positive control and received 50mg/kg/bw/day of aspartame alone. Group C received 50mg/kg/bw/day of aspartame and 250mg/kg/bw/day of ethanolic extract of Sacoglottis gabonensis leaf. Group D receive 50mg/kg/bw/day of aspartame and 250mg/kg/bw/day of ethanolic extract of S. gabonensis bark. Group E received 50mg/kg/bw/day of aspartame and 250mg/kg/bw/day of a combination of bark and leaf extract. Group F received 50mg/kg/bw/day of aspartame and 500mg/kg/bw/day of a combination of bark and leaf extract. All the groups were exposed to their treatment by oral gavage for 30, 60 and 90days. Feed was withdrawn from the animals 24hours before the termination of experiment. For Biochemical analysis, blood samples were collected by ocular puncture into sterile tubes and serum separated by centrifugation at 2500 g for 10 mins and stored for determination of some liver biomarkers using their respective kits. For histopathological analysis, 0.5g of Liver was fixed in 10% neutral formalin and sectioned with a digital microtome (AO Spencer, No. 820) at 5 µm thick. Histological sections mounted on slides were stained with Haematoxylin and Eosin (H&amp;E). Photomicrographs were generated at X40 magnification and interpreted.&#x0D; Results: There was significant (p&lt;0.05) increase in Malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the group B administered aspartame only when compared with the groups co-administered extracts of leaf, bark and combination of Sacoglottis gabonensis. Also, a significant (p&lt;0.05) decrease in the concentrations of superoxide dismutase (SOD), gluthathione (GSH) and catalase (CAT) was recorded in group B when compared to other groups across the experimental period. Groups coadministered S. gabonensis extract showed a significant increase in SOD, GSH and CAT and decrease in MDA compared to the positive control. Histopathological analysis shows the liver epithelium of the negative control group being filled with healthy normal hepatocytes, while liver exposed to aspartame alone (positive control) showed degenerated hepatocytes, multiple necrotic and apoptotic cells. The liver epithelium exposed to aspartame and the extracts of S. gabonensis showed regenerating hepatocytes with many binucleated cells seen, few necrotic and apoptotic bodies also seen.&#x0D; Conclusion: The significant decrease in liver injury biomarkers, increase in the oxidative stress biomarkers and the increased number of hepatocytes captured in the liver epithelium of animals co-administered S. gabonensis shows the novel property of S.gaboensis as an antioxidant defense against oxidative damage.

TRPM2 Channel Inhibition Attenuates Amyloid β42-Induced Apoptosis and Oxidative Stress in the Hippocampus of Mice.

Alzheimer's disease (AD) is characterized by the increase of hippocampal Ca2+ influx-induced apoptosis and mitochondrial oxidative stress (OS). The OS is a stimulator of TRPM2, although N-(p-amylcinnamoyl)anthranilic acid (ACA), 2-aminoethyl diphenylborinate (2/APB), and glutathione (GSH) are non-specific antagonists of TRPM2. In the present study, we investigated the protective roles of GSH and TRPM2 antagonist treatments on the amyloid β42 peptide (Aβ)-caused oxidative neurotoxicity and apoptosis in the hippocampus of mice with AD model. After the isolation of hippocampal neurons from the newborn mice, they were divided into five incubation groups as follows: control, ACA, Aβ, Aβ+ACA, and Aβ+GSH. The levels of apoptosis, hippocampus death, cytosolic ROS, cytosolic Zn2+, mitochondrial ROS, caspase-3, caspase-9, lipid peroxidation, and cytosolic Ca2+ were increased in the primary hippocampus cultures by treatments of Aβ, although their levels were decreased in the neurons by the treatments of GSH, PARP-1 inhibitors (PJ34 and DPQ), and TRPM2 blockers (ACA and 2/APB). The Aβ-induced decreases of cell viability, cytosolic GSH, reduced GSH, and GSH peroxidase levels were also increased in the groups of Aβ+ACA and Aβ+GSH by the treatments of ACA and GSH. However, the Aβ-caused changes were not observed in the hippocampus of TRPM2-knockout mice. In conclusion, the present data demonstrate that maintaining the activation of TRPM2 is not only important for the quenching OS and neurotoxicity in the hippocampal neurons of mice with experimental AD but also equally critical to the modulation of Aβ-induced apoptosis. The possible positive effects of GSH and TRPM2 antagonist treatments on the amyloid-beta (Aβ)-induced oxidative toxicity in the hippocampus of mice. The ADP-ribose (ADPR) is produced via the stimulation of PARP-1 in the nucleus of neurons. The NUT9 in the C terminus of TRPM2 channel acts as a key role for the activation of TRPM2. The antagonists of TRPM2 are glutathione (GSH), ACA, and 2/APB in the hippocampus. The Aβ incubation-mediated TRPM2 stimulation increases the concentration of cytosolic-free Ca2+ and Zn2+ in the hippocampus. In turn, the increased concentration causes the increase of mitochondrial membrane potential (ΔΨm), which causes the excessive generations of mitochondria ROS and the decrease of cytosolic GSH and GSH peroxidase (GSH-Px). The ROS production and GSH depletion are two main causes in the neurobiology of Alzheimer's disease. However, the effect of Aβ was not shown in the hippocampus of TRPM2-knockout mice. The Aβ and TRPM2 stimulation-caused overload Ca2+ entry cause apoptosis and cell death via the activations of caspase-3 (Casp/3) and caspase-9 (Casp/9) in the hippocampus. The actions of Aβ-induced oxidative toxicity were modulated in the primary hippocampus by the incubations of ACA, GSH, 2/APB, and PARP-1 inhibitors (PJ34 and DPQ). (↑) Increase. (↓) Decrease.

Toxicogenetic assessment of a pre-workout supplement: In vitro mutagenicity, cytotoxicity, genotoxicity and glutathione determination in liver cell lines and in silico ADMET approaches.

The benefits of practicing physical activity, such as weight loss and control, are commonly associated with caloric restriction diets and may be improved by the ingestion of thermogenic and ergogenic supplements. However, there is a lack of safety data on commonly marketed nutritional supplements. Therefore, this investigation aims to evaluate a pre-workout supplement for mutagenicity using the Ames test, hepatocytoxicity in HepG2 and F C3H cells after 24h, 48h and 72h, genotoxicity using the CBMN assay, determination of gluthatione activity and computational prediction of the three major isolated compounds present in the supplement. The mutagenicity test showed a mutagenic response in TA98 His+ revertants of 5mg/plate in the presence of metabolic activation, cytotoxicity in TA98 of 5mg/plate in the absence of metabolic conditions, and in TA102 of 0.5mg/plate both in the presence and absence of metabolic activation. In our in vitro eukaryotic cell viability, WST-1, LDH and alkaline phosphatase assays, the supplement showed hepatocytotoxicity both dose-dependently and time-dependently. In the cytokinesis blocking micronuclei assay, the supplement induced micronuclei, nuclear buds, nucleoplasmatic, bridge formation, and a decreased in nuclear division. In addition, the supplement decreased intra and extracellular GSH. Computational analysis showed that the three isolated compounds most present in the supplement have the potential to cause hepatotoxicity. In the present investigation, the pre-workout supplement induced mutagenic, genotoxic, and cytotoxic responses and GSH decrease. Thus, considering food safety and public health sanitary vigilance, the consumption of this pre-workout supplement may harm the health of its consumers.