Increased GSH Levels Research Articles

Beneficial Microorganisms: Sulfur-Oxidizing Bacteria Modulate Salt and Drought Stress Responses in the Halophyte Plantago coronopus L

Land degradation due to salinity and prolonged drought poses significant global challenges by reducing crop yields, depleting resources, and disrupting ecosystems. Halophytes, equipped with adaptive traits for drought and soil salinity, and their associations with halotolerant microbes, offer promising solutions for restoring degraded areas sustainably. This study evaluated the effects of halophilic sulfur-oxidizing bacteria (SOB), specifically Halothiobacillus halophilus, on the physiological and biochemical responses of the halophyte Plantago coronopus L. under drought and salt stress. We analyzed the accumulation of ions (Na, Cl, K) and sulfur (S), along with growth parameters, glutathione levels, photosynthetic pigments, proline, and phenolic compounds. Drought significantly reduced water content (nearly 10-fold in plants without SOB and 4-fold in those with SOB). The leaf growth tolerance index improved by 70% in control plants and 30% in moderately salt-stressed plants (300 mM NaCl) after SOB application. SOB increased sulfur content in all treatments except at high salinity (600 mM NaCl), reduced toxic sodium and chloride ion accumulation, and enhanced potassium levels under drought and moderate salinity. Proline, total phenolic, and malondialdehyde (MDA) levels were highest in drought-stressed plants, regardless of SOB inoculation. SOB inoculation increased GSH levels in both control and 300 mM NaCl-treated plants, while GSSG levels remained constant. These findings highlight the potential of SOB as beneficial microorganisms to enhance sulfur availability and improve P. coronopus tolerance to moderate salt stress.

The impact of N-acetylcysteine on lactate, biomarkers of oxidative stress, immune response, and muscle damage: A systematic review and meta-analysis.

N-acetylcysteine (NAC) is a compound whose mechanism of action is intricately linked to the provision of cysteine for glutathione synthesis. It has been used in medicine and has also made significant inroads into sports, as it can modify the levels of several biomarkers, including those of oxidative processes, inflammation and muscle damage after exercise. Because the effectiveness of NAC supplementation is unclear, the primary objective of the present study was to perform a meta-analysis elucidating how NAC supplementation alters the concentrations of GSH (glutathione), GSSG (glutathione disulfide), TBARS (thiobarbituric acid reactive substances), IL-6 (interleukin 6), TNF-α (tumour necrosis factor alpha), CK (creatine kinase), lactate, and muscle soreness after physical exertion. Suitable studies were searched for from February to September 2023, and the results of those included (n = 20) indicate that NAC supplementation significantly diminishes both muscle soreness (p = 0.03; the mean difference (MD) of NAC's effect was -0.43 with a 95% confidence interval (CI), -0.81, -0.04) and lactate concentrations after exercise (p = 0.03; the MD -0.56 mmol/L; 95% CI, -1.07, -0.06). A substantial decrease was observed in concentrations of IL-6 (p = 0.03; the standardized MD (SMD) was -1.71; 95% CI, -3.26, -0.16) and TBARS (p = 0.02; SMD was -1.03, 95% CI, -1.90, -0.15). Furthermore, an elevation in GSH concentration was observed following supplementation. However, we saw no significant effect of NAC on TNF-α, CK or GSSG concentrations. NAC supplementation holds promise for attenuating muscle soreness, lactate, TBARS and IL-6 concentrations and increasing GSH level following physical exertion.

Dimethyl Fumarate Reduces Methylglyoxal-derived Carbonyl Stress Through Nrf2/GSH Activation in SH-SY5Y Cells.

Carbonyl stress refers to the excessive accumulation of advanced glycation end products (AGEs) in mammalian tissues. This phenomenon plays a significant role in the pathogenesis of various diseases, including diabetes, chronic renal failure, arteriosclerosis, and central nervous system (CNS) disorders. We have previously demonstrated that an increase in glutathione concentration, dependent on the nuclear factor erythroid 2-related factor 2 (Nrf2) system, provides a potent cytoprotective effect against Methylglyoxal (MGO)-induced carbonyl stress. Meanwhile, dimethyl fumarate (DMF), known for its Nrf2-activating effects, was recently approved as a treatment for multiple sclerosis (MS), a neurodegenerative disease. DMF is a first line therapy for relapsing-remitting MS and may also be effective for other neurodegenerative conditions. However, the detailed mechanisms by which DMF mitigates neurodegenerative pathologies remain unclear. This study investigates the impact of DMF on anticarbonyl activity and its underlying mechanism focusing on the accumulation of carbonyl protein in the cell. MGO, a glucose metabolite, was used to induce carbonylation in the neuronal cell line. MGO is a typical carbonyl compound that readily reacts with arginine and lysine residues to form AGE-modified proteins. Methylglyoxal-derived hydroimidazolone 1 (MG-H1) often forms uncharged, hydrophobic residues on the protein surface, which can affect protein distribution and lead to misfolding. Our findings indicate that DMF increases levels of glutathione (GSH), glutamate cysteine ligase modifier subunit (GCLM), and nuclear Nrf2 in SH-SY5Y cells. Importantly, DMF pretreatment significantly reduced the accumulation of MG-H1-modified proteins. Furthermore, this effect of DMF was diminished when Nrf2 expression was suppressed and when GCL, a rate-limiting enzyme in GSH synthesis, was inhibited. Thus, the increase in GSH levels, leading to the activation of the Nrf2 pathway, a key factor in DMF's ability to suppress the accumulation of MG-H1-modified proteins. This study is the first to demonstrate that DMF possesses strong anticarbonyl stress activity in neuronal cells. Therefore, future research may extend the application of DMF to other CNS diseases associated with carbonyl stress, such as Alzheimer's and Parkinson's disease.

Enhancing porcine oocyte quality and embryo development through natural antioxidants

During fetal development, primordial oocytes maintain their developmental potential through a ROS-minimizing metabolic mechanism. Maturation increases ROS levels, causing stress and damage, which are countered by in vivo antioxidants. In vitro maturation (IVM) worsens this due to fewer antioxidant presence and medium factors. To address this, we evaluated the effects of incorporating various natural antioxidants in the porcine oocyte IVM media. Our findings revealed that 10 μM Dendrobine (DEN), 1 μM Polydatin (PD), 20 μM Limonin (LIM), and 25 μM Nobiletin (NOB) significantly improved the first polar body extrusion rates (p < 0.05), reduced ROS, and increased GSH levels. Individual addition of 100 μg/mL Lycium barbarum polysaccharides (LBP), 0.1 μM Kaempferol (KAE), 250 μM Salidroside (SAL), 10 μM Curcumin (CUR), DEN, PD, LIM, and NOB to the porcine IVM system showed that KAE, LIM, NOB, and LBP treatments yielded the most favorable results. At the gene level, LIM, LBP, and NOB were found to upregulate the expression levels of GPX1, SIRT1, and TFAM, while downregulating Caspase3 and increasing the BCL2/BAX ratio. The inclusion of LIM, NOB, and LBP, either alone or in combination, into the IVM media effectively alleviated oxidative stress in porcine oocytes, decreased cell apoptosis, preserved mitochondrial membrane potential, and enhanced the blastocyst rate. These results offer valuable insights for optimizing the porcine oocyte IVM culture system.

Cefiderocol has immunoregulative effects in LPS-induced vitro experimental model via inhibiting inflammation and ferroptosis

BackgroundCefiderocol is a new catecholamine-containing siderophore cephalosporin. It, however, remains unclear how cefiderocol modulates the immune response of the host. ObjectivesThis study elucidated whether cefiderocol exerts immunoprotective effects in an in vitro experimental model induced with lipopolysaccharide (LPS). MethodsMouse macrophage RAW 264.7 cells were exposed to LPS (100 ng/mL) or LPS + cefiderocol (40 mg/L) to assess the immunomodulatory effect of cefiderocol in vitro. ELISA was performed on cell culture supernatants to estimate cytokine levels. Ferroptosis level was also quantified by detecting intracellular reactive oxygen species (ROS) and iron levels through flow cytometry analysis. Malondialdehyde (MDA) and glutathione (GSH) levels were estimated by ELISA. We conducted western blotting assay for evaluating key ferroptosis pathway proteins. ResultsCefiderocol alleviated LPS-induced inflammation by reducing IL-6, TNF-α, and IL-1β production levels and enhancing the IL-10 production level. Further analysis to determine the underlying mechanism revealed that cefiderocol inhibited ferroptosis; this was confirmed by reduced ROS, MDA, and Fe2+ ion levels; increased GSH levels; upregulated expression of solute carrier family 7 member 11, glutathione peroxidase 4, nuclear factor erythroid 2-related factor 2, and ferroptosis suppressor protein 1; and downregulated expression of acyl-CoA synthetase long-chain family member 4. ConclusionsCefiderocol may play a key role in reducing inflammation by decreasing inflammatory cytokine release and suppressing ferroptosis.

Protective Effects of Ascorbic Acid Against Cadmium-Induced Toxicity in the Placenta and Fetus of Rats.

This study aimed to determine the protective role of l-ascorbic acid in a pregnant rat model of cadmium-induced toxicity. Cadmium is a toxic heavy metal that can seriously harm placenta and fetus tissue in pregnant women. Forty-two healthy female Wistar albino rats (250-300 g weight and 14-16 weeks) were randomly distributed into six equal groups (n = 7): control, cadmium 1 mg (CD1), cadmium 5 mg (CD5), ascorbic acid (AA), CD1+AA, CD5+AA. Cadmium was administered to pregnant rats by oral gavage every other day, and/or AA (200 mg) was administered every day. At the end of pregnancy (Day 21), blood, placenta, and fetuses were collected from rats. The results indicated that cadmium-induced oxidative stress by increasing the level of MDA and by decreasing the levels of GSH, SOD, and CAT activity in the serum of maternal. However, AA administration significantly decreased MDA levels and increased GSH levels, SOD, and CAT activity (p < 0.05). Cadmium (5 mg/kg) exposure significantly increased creatinine levels compared to AA and CD1+AA groups (p < 0.05). In addition, AA (200 mg/kg) significantly attenuated cadmium-induced histopathological alteration in the placental and fetal tissues. In conclusion, AA may prevent cadmium toxicity in maternal and fetal tissues, as it regulates oxidative imbalance in pregnant rat tissues and alleviates histopathological changes.

Glutathione regulates CIA-activated splenic-lymphocytes via NF-κB/MMP-9 and MAPK/PCNA pathways manipulating immune response

Reduced glutathione (GSH) is an antioxidant involved in redox homeostasis, and recently regarded as an inducer of Reductive stress. Its immune-regulatory effects on lymphocytes have not been extensively studied. This study is based on the finding that much increased GSH level in collagen-induced arthritis (CIA) rat spleen, and aimed to investigate the effects of GSH (0, 1, 10, 100 mM) on normal and immune-stimulated spleen lymphocytes respectively. The elevated GSH level is associated with the increased levels of inflammatory factors; especially the increased DPP1 activity indicated immune-granulocytes activation in CIA rat spleen. Exogenous GSH had different influences on normal and CIA lymphocytes, affecting intracellular levels of GSH, Glutathione-S-transferases (GSTs) and Reactive oxygen species (ROS); as well as the expressions of NF-κB, MMP-9, Bcl-2, GST, P38, PCNA and TLR4. The increased extracellular GSH level disturbed redox homeostasis and induces reductive stress to spleen lymphocytes, which decreased intracellular GSH concentration and influenced the MAPK/PCNA and NF-κB/MMP-9 signaling pathways, as well as cell cycles respectively, leading to cell senescence/ferroptosis /apoptosis. This study also revealed the multiple faces of GSH in regulating spleen lymphocytes, which depends on its levels in tissue or in cells, and the activation status of lymphocytes. These findings indicate the immune-regulatory role of GSH on spleen-lymphocytes, and the high level GSH in CIA rat spleens may contribute to CIA development.

Evaluation of the Effect of Gum Arabic on the Histological and Physiological Changes in the Liver of Albino Rats Exposed to Bisphenol A

We designed this work in order to study the protective effect of aqueous extract of gum arabic (GA) from oxidative damage induced by bisphenol A(BPA). This study was conducted on 35 male laboratory Albino rats of Sprague Dawley strain (165-210 grams) and divided into five groups. Each group included 7 rats. The experiment was performed at the animal house of Biology (College of Education for Pure Sciences). The experiment continued for 90 days under conditions Standard laboratory, as follows: The first group was the control; the second group had GA taken orally; the third group had BPA taken orally; the fourth group had GA taken first, followed by BPS, and the fifth group had BPA taken first, followed by GA. According to the above results clearly, Serum levels of AST, ALT and Lipid profile (Cholesterol, Triglyceride) indicated a highly significant increase in these parameters at group 3, While the fourth and fifth groups show significant reductions in AST, ALT, cholesterol, triglycerides, and MDA, also significant increases in GSH levels, While the histological changes in the third group were represented by the presence of a state of blood congestion with depletion of glycoprotein and degeneration of some cells, in addition to the presence of a state of necrosis of liver cells, while it was not observed severe histological changes when compared to third group in both fourth and fifth groups. In Short, the above results indicated that GA treatment for BPA-induced liver injury had Therapeutic effect through anti-free radical formation and functional role as free scavenger.

Glutathione and Selenium Supplementation Attenuates Liver Injury in Diethylnitrosamine-Induced Hepatocarcinogenic Mice by Enhancing Glutathione-Related Antioxidant Capacities.

Excess oxidative stress and inadequate antioxidant capacities are critical features in the development of hepatocellular carcinoma. This study aimed to determine whether supplementation with glutathione (GSH) and/or selenium (Se), as antioxidants, attenuates diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. C57BL/6J male mice were randomly assigned to control, DEN, DEN + GSH, DEN + Se, and DEN + GSH + Se groups for 20 weeks. Daily supplementation with GSH and/or Se commenced in the first experimental week and continued throughout the study. DEN was administered in weeks 2-9 and 16-19 of the experimental period. DEN administration induced significant pathological alterations of hepatic foci, evidenced by elevated levels of liver function, accompanied by high malondialdehyde (MDA) levels; low GSH levels; and glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) activities. Supplementation with GSH and Se significantly ameliorated liver pathological changes, reducing liver function and MDA levels while increasing GSH levels and GPx, GR, and GST activities. Notably, combined supplementation with GSH and Se more effectively increased the GSH/glutathione disulfide ratio and GPx activity than individual supplementation. Supplementation with GSH and Se attenuated liver injury in DEN-induced hepatocarcinogenic mice by enhancing GSH and its related antioxidant capacities, thereby mitigating oxidative damage.

Trans-chalcone ameliorates CCl4-induced acute liver injury by suppressing endoplasmic reticulum stress, oxidative stress and inflammation

BackgroundAcute liver injury serves as a crucial marker for detecting liver damage due to toxic, viral, metabolic, and autoimmune exposures. Due to the response to adverse external stimuli and various cellular homeostasis, Endoplasmic reticulum stress (ERS), Oxidative stress, and Inflammation have great potential for treating liver injury. Trans-chalcones (TC) is a polyphenolic compound derived from a natural plant with anti-oxidative and anti-inflammatory abilities. Here, TC was aimed to attenuate liver injury by triggering ER stress, oxidative stress, inflammation, and apoptosis. A single dose of carbon tetrachloride (CCl4) 1 mL/kg was administered intraperitoneally into C57BL6 mice to construct an in vivo NAFLD model, whereas AML12 cells were treated with lipopolysaccharides (LPS) to construct an in vitro NAFLD model. The mice used in the experiment were randomly assigned to two groups: a 12-hour set and a 24-hour set. Forty-nine mice were randomly divided into seven groups, the control group (Group I), TC group (Group II) 10 mg/kg TC, negative control group (Group III) CCl4, TC + CCl4 groups (Groups IV−VI), mice were subcutaneously treated with (5, 10, and 20) mg/kg of TC for three consecutive days before the CCl4 injection and the positive control group (Group VII) received 10 mg/kg Silymarin. After the experiment, serum transaminase, liver histological pathology, hepatic expression levels ERS, oxidative stress, and inflammation-related markers were assessed. TC pre-treatment significantly alleviates the expression of ER stress, oxidative stress, inflammatory cytokines, and apoptosis in both in vivo and in vitro models of liver injury. TC treatment significantly reduced serum transaminase levels (ALT and AST), and improved liver histopathological scores. TC administration also led to a reduction in MDA levels and the suppression of ROS generated by CCl4 in hepatic tissue, which contributed to an increase in GSH levels. The protective effect of TC on the liver injury mouse model was achieved by inhibiting hepatocyte apoptosis. Moreover, TC pre-treatment dramatically decreased the protein levels of ER stress indicators such as CHOP, Bip, Ero-Lα, IRE1α, PERK, Calnexin, and PDI when compared to the CCl4-only treated group. TC exerts hepatoprotective effects against CCl4-induced acute liver injuries in mice by modulating ERS, oxidative stress, and inflammation. These results suggest that TC pre-treatment at a dose of (20 mg/kg BW) was as effective as silymarin (10 mg/kg) in preventing CCl4-induced acute liver injury. Further investigations are necessary to elucidate the precise molecular mechanisms underlying the hepatoprotective effects of TC and to explore its therapeutic potential in clinical trials.

Effects of long-term Tai Chi vs. aerobic exercise on antioxidant activity and cognitive function in individuals with Parkinson’s disease

An imbalance between the generation of reactive oxygen species and the body’s antioxidant defense mechanisms is closely related to the development and progression of Parkinson’s disease (PD). Considering that physical exercise is a potential therapeutic intervention for modulating oxidative stress markers and cognitive function in PD, the primary purpose of this study was to compare the effects of different long-term exercise modalities on antioxidants and cognitive performance in patients with PD. In addition, the secondary purpose was to explore whether changes in the levels of these biochemical markers are associated with alterations in cognitive performance pre- and post-intervention. In all, 61 participants were randomly divided into the aerobic exercise (AE, n=20), Tai Chi exercise (TCE, n=21), or control (n=20) group. Blood samples were collected before and after a 12-week intervention period for the analysis of antioxidant markers [leukocyte 8-hydroxydeoxyguanosine (8-OHdG), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-Px), oxidized glutathione (GSSG), superoxide dismutase (SOD), and uric acid (UA)]. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Although no significant changes were observed in the activity of 8-OhdG, GSH-Px, GSSG, GSH:GSSG ratio, SOD, and cognitive performance in the AE and TCE groups, the 12-week AE intervention led to a significant increase in CAT and GSH levels, along with a significantly decrease in UA levels among individuals with PD. Conversely, the TCE intervention resulted in a significant increase in GSH levels. However, SOD activity and MMSE scores were significantly decreased after 12 weeks in the control group. The correlations between changes in MMSE scores and changes in the levels of GSH and UA prior to and after the intervention reached significance in the AE group. Thus, long-term AE and TCE might serve as effective strategies for reducing oxidative damage and preserving cognitive function in PD, with AE exhibiting greater benefits compared with TCE. These findings hold potential clinical relevance as complementary measures to standard medical treatments and alternative therapies, such as antioxidant supplements and dietary adjustments, particularly for individuals in the early stages of PD.

Curcumin alleviates septic lung injury in mice by inhibiting TXNIP/TRX-1/GPX4-mediated ferroptosis

To investigate whether curcumin alleviates septic lung injury by inhibiting ferroptosis through modulating the TXNIP/TRX-1/GPX4 pathway. Male C57BL/6 mice were randomly divided into Sham group, cecal ligation puncture (CLP)-induced sepsis group, CLP with curcumin treatment (50, 100, and 200 mg/kg) groups, and CLP with both curcumin (200 mg/kg) and TRX-1 inhibitor PX-12 (25 mg/kg) treatment group. Inflammatory factors, MDA, MPO, and GSH levels in the lung tissue of the mice were detected. Beas-2B cells stimulated with lipopolysaccharide (LPS; 1 μg/mL) were treated with 2.5, 5, or 10 μmol/L curcumin or with 10 μmol/L curcumin combined with 5 μmol/L PX-12, and the changes in MDA, Fe2+ and ROS levels were assessed. Western blotting was performed to detect the protein expressions of TXNIP, TRX-1, GPX4 and X-CT in both the mouse lung tissues and Beas-2B cells. The mice with CLP-induced sepsis showed severe lung injury with elevated expressions of IL-6, IL-1β, TNF-α, MDA and MPO and decreased GSH expression. In Beas-2B cells, LPS stimulation significantly increased MDA and Fe2+ levels and ROS release, increased TXNIP protein expression, and lowered the protein expression levels of TRX-1, GPX4 and X-CT, and these changes were also observed in the septic mice. Curcumin treatments at different concentrations obviously alleviated lung injury in the septic mice and reduced LPS-induced injury in Beas-2B cells. Curcumin significantly decreased the release of inflammatory factors, MDA and MPO, increased GSH level, lowered Fe2+, MDA and ROS levels, increased TXNIP protein expression, and lowered the protein expressions of TRX-1, GPX4 and X-CT in both septic mouse lung tissues and LPS-stimulated Beas-2B cells. The protective effect of curcumin was effectively blocked by PX-12 treatment. Curcumin inhibits ferroptosis and alleviates septic lung injury in mice by elevating TRX-1 and GPX4 and decreasing TXNIP in the lung tissue.

Nicorandil attenuates lithocholic acid-induced hepatotoxicity in mice through impeding oxidative stress, inflammation and apoptosis

This study was performed to explore the beneficial protective impact of nicorandil (Nico) against lithocholic acid (LCA)-induced hepatotoxicity. Materials and methods: Mice received Nico (50 and 100 mg/kg. orally) for 7 days and LCA (125 mg/kg, i.p.) was injected for the last 4 days two times daily. Results: Nico improved both structural and functional abnormalities induced by LCA. Nico significantly decreased serum levels of transaminases, ALP, GGT and markedly elevated albumin levels. Additionally, Nico mitigated oxidative stress; it decreased contents of MDA and NO and increased GSH level and SOD activity. Moreover, Nico markedly decreased the elevated levels of TNF-α, JNK, Bax, Caspase-3 and iNOS, and increased the levels of eNOS in hepatic tissues. Furthermore, Nico substantially decreased the expression of NFκBp65 in hepatic tissues. Histopathological and transmission electron microscopy findings further supported these biomarkers. Conclusion: Nico might be used as an adjuvant medication to prevent LCA-induced hepatotoxicity, pending further clinical research, through impeding oxidative stress, inflammation and apoptosis.

Dietary inclusion of cyanobacteria Arthrospira (Spirulina platensis) spp. decreases the aggravating effect of hemin from red meat in a rat colorectal carcinogenesis model

Colorectal cancer (CRC) risk, associated with a high intake of red/processed meat, may be related to hemin. A potential chemopreventive agent, Arthrospira (Spirulina platensis) spp. (AP) is a cyanobacteria employed as a functional food with the potential to reduce malnutrition in developing countries. Thus, we assessed the effects of dietary AP against hemin-promoting effects in a dimethylhydrazine (DMH)-induced colorectal carcinogenesis model. Male Sprague-Dawley rats were allocated into five groups. G1–G4 received four subcutaneous DMH injections (40 mg/kg body weight, twice a week for 2 weeks) and G5 received DMH vehicle. At weeks 4 to 16, groups were fed a balanced diet (BD, G1 and G5), BD containing 2 % AP (20 g powder/kg chow, G2), BD containing hemin (0.32 g/kg chow, G3) or BD containing hemin+2 % AP (G4), respectively. Hemin group (G3) increased aberrant crypt foci (ACF) development, malondialdehyde (MDA), and Nox-1 levels and reduced glutathione (GSH) and GSH-Px levels in colonic mucosa when compared to DMH group (G1). In contrast, the dietary hemin+2 % AP regimen (G4), reduced both preneoplastic lesion development and MDA levels while increased GSH levels, compared to the DMH+hemin group (G3). Dietary AP may reduce hemin-promoting effects by modulating oxidative stress and ACF lesions.

Mitochondrial damage precedes the changes of glutathione metabolism in CdCl2 treated neuronal SH-SY5Y cells

Cadmium crosses the blood-brain barrier inducing damage to neurons. Cell impairment is predominantly linked to oxidative stress and glutathione (GSH) depletion. On the other hand, several reports have described an increase of GSH levels in neuronal cells after CdCl2 exposure. Therefore, the aim of the present report was to investigate the relation between changes in GSH levels and mitochondrial damage in neuronal cells after CdCl2 treatment. To characterize neuronal impairment after CdCl2 treatment (0–200 μM) for 1–48 h, we used the SH-SY5Y cell line. We analyzed GSH metabolism and determined mitochondrial activity using high-resolution respirometry. CdCl2 treatment induced both the decreases and increases of GSH levels in SH-SY5Y cells. GSH concentration was significantly increased in cells incubated with up to 50 μM CdCl2 but only 100 μM CdCl2 induced GSH depletion linked to increased ROS production. The overexpression of proteins involved in GSH synthesis increased in response to 50 and 100 μM CdCl2 after 6 h. Finally, strong mitochondrial impairment was detected even in 50 μM CdCl2 treated cells after 24 h. We conclude that a significant decrease in mitochondrial activity can be observed in 50 μM CdCl2 even without the occurrence of GSH depletion in SH-SY5Y cells.

Neuroprotective effect of Myrtus communis against ionizing radiation-induced brain injury: Insights from histopathological and biochemical analysis in rats: TROD-GROG 005

AimTo investigate the potential radioprotective effects of Myrtus communis on brain tissue. MethodsThirty female rats were divided into four groups. The control group (C) was applied with oral saline solution (SF) for four days. Myrtus communis (MC) groups started to receive MC (100 mg/kg, oral) either four days before (R + preMC) or immediately after (R + MC) irradiation for four days. Irradiation was applied 10 Gy in a single fraction. All rats were sacrificed on the fourth day of irradiation. Malondialdehyde (MDA), nitric oxide (NO), and glutathione (GSH) levels, myeloperoxidase (MPO), superoxide dismutase (SOD), and tissue factor activities (TFa) were determined for biochemical analysis. Hematoxylin&Eosin staining was done for histopathological analyses, and electrophoretic analyses were performed. ResultsNO, MDA, and MPO levels were higher in all irradiated groups compared with the C group. MC administration decreased NO, MDA, and MPO levels in R + preMC and R + MC groups. MC administration increased GSH levels. TFa activity decreased in R groups but did not change with MC administration compared to the C group. Radiation-induced brain tissue injury decreased, and morphologically normal neurons were observed in both MC-added groups. ConclusionMyrtus communis has a potential neuroprotective effect on brain tissue, attributed to its antioxidative, anti-inflammatory, and anti-lipid peroxidative properties.

Effects of in utero benzo[a]pyrene exposure on the testis of rats during puberty and the protective effect of atorvastatin.

Benzo[a]pyrene (BaP) is a contaminant that is generated in the environment through processes such as smoke, incomplete combustion of fossil fuels, vehicle exhaust emissions, entry into the body is through inhalation, and consumption of contaminated food. It is an omnipresent environmental pollutant with unavoidable exposure. BaP metabolites are observed in the male reproductive system, especially in the testes and epididymis of animals, and are responsible for reduced testicular and epididymal function. The protective effect of atorvastatin (ATV) on testicular damage was investigated previously. The aim of the present study was to investigate the protective effect of ATV on testicular toxicity induced by benzo[a]pyrene (BaP) during pregnancy in Wistar rats. This experimental laboratory study involved 40 adult rats, divided into seven groups and maintained under standard environmental conditions. The groups received different diets [control, corn oil, ATV (10 mg/kg), BaP (10 and 20 mg/kg), and ATV + BaP (10 and 20 mg/kg)] at gestation Days 7-16, orally. Male offspring were examined 10 weeks after birth. Testis and serum samples were collected, and testosterone level, malondialdehyde (MDA), and glutathione (GSH) were measured. Histological and immunohistochemical assays were performed under a light microscope. Statistical analysis was conducted using SPSS, with analysis of variance and Tukey tests to assess significant differences between groups. ATV significantly reduced MDA, a marker of lipid peroxidation and oxidative stress in rat testes following BaP administration. Treatment with ATV at doses of 10 mg/kg increased GSH levels, correcting disruptions in the antioxidant system caused by BaP. Testosterone concentration in rats treated with ATV and BaP substantially prevented the decrease induced by BaP. Histomorphometry revealed that ATV significantly prevented the detrimental effects of BaP on the thickness of spermatogenic epithelium and the diameter of seminiferous tubules. Under ATV treatment, testicular tissue histopathology improved, and spermatogenesis returned to a almost back to normal state. Caspase-3 expression decreased, and apoptosis activity in testicular tissue improved under ATV treatment, indicating a positive effect of ATV in reducing apoptotic damage caused by BaP. In conclusion, exposure to BaP can induce oxidative stress-related damage to testicular tissue, as evidenced by an increase in MDA levels, which ATV treatment can mitigate. Additionally, ATV enhances intracellular antioxidant GSH and protects the testes against BaP-induced damage while increasing testosterone levels, which are reduced due to exposure to BaP.

Abstract Tu138: Tandem Mass Tagging (TMT)-based Identification of Proteome Signatures for Ischemia-Reperfusion Injury in Swine

Background: The composition of proteins in blood plasma mirrors the physical changes occurring in the course of disease pathogenesis. Currently available clinical markers are insufficient to predict the actual damage and the redox changes in response to ischemia. Hence, we identified novel redox markers for ischemia/reperfusion (I/R) in swine using TMT-proteomics. Methodology: We employed TMT-10plex isobaric labeling-based quantitative proteomics to track the plasma proteome in Sus Scorfa pigs subjected to surgical I/R at different time points. Plasma samples were collected before ischemia, at 1-hr after ischemia (baseline), and 4-hr, 24-hrs, and 7 days following reperfusion. Results: An average of 4853 spectra and a total of 457 proteins were identified, ensuring a 1% false discovery rate for peptides and proteins with at least two distinct peptides. Pre-ischemia plasma samples served as the control group in all the analyses. TMT analysis revealed temporal changes in the plasma proteome with a prominent shift at 4 hours after I/R insult. To investigate the significantly changed proteins (&gt;1.5 fold), a temporal analysis was carried out. Notably, endopin-1, a serpin protein family member, and fibronectin B were detectable in the plasma following 4 hours of ischemia-reperfusion, indicating the release of these proteins in the circulation during the ischemia-reperfusion. A positive correlation was observed between the redox proteins (i.e., catalase and glutathione peroxidase) with the serpin proteins in the plasma. Biochemical analysis of circulating glutathione, a small-molecular antioxidant, revealed a reductive redox after 60 minutes of Ischemia (hypoxic condition) but this was shifted to an oxidative milieu at 4hrs following reperfusion (hyperoxia) in the adult pigs subjected to I/R insult. Interestingly, we noticed a significant increase in GSH levels and a decrease in catalase levels at 24 hours following I/R, suggesting a compensatory biochemical response in association with repair after I/R insult/injury in the heart. These results correlated with the increased circulating LDH levels indicating the rate of tissue damage following I/R. Conclusion: The present study reveals the presence of a previously unexplored Serpin protein member, endopin-1, during I/R. Understanding the kinetics of endopin-1 expression along with the shift in redox state can help unravel its role in the progression and resolution phases of I/R injury.

Influence of Aframomum sceptrum Treatment on Hepatic Toxicity Induced by Monosodium Glutamate in Albino Rats

Monosodium glutamate (MSG) is commonly used as a culinary flavouring, although research suggest that it is toxic to people and laboratory animals, especially in high dosages. The study goal is to determine the impact of Aframomum sceptrum (ataiko) treatment on hepatic induced toxicity by MSG. Thirty-six albino rats (male) with weight of 120 to 210 g were used for the study. The rats were separated into 6 groups in which each group contains six rats. Group 1: normal control. Group 2: MSG only. Group 3 and 4 were given MSG and then treated with 250 and 350 mg/kg b.wt of A. sceptrum extract respectively. Group 5 and 6 were administered only 250 and 350 mg/kg b.wt of A. sceptrum extract, respectively. The MSG groups were given intra-peritoneal injection of MSG solution at single dose of 4253 mg/kg b.wt. A. sceptrum extract was administered three times a week for four weeks beginning two days after the MSG induction. Liver function markers such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and oxidative stress markers such as reduced glutathione (GSH) and malondialdehyde (MDA) were determined in serum and liver. Also, glucose was determined in the serum. The results showed that there were significant (p &lt; 0.05) increased in glucose, AST, ALT and MDA in serum and liver, and decreased in GSH level in the liver of rats given MSG only when compared with normal control. However, A. sceptrum administration significantly (p &lt; 0.05) decreased glucose, AST, ALT and MDA in the serum and liver, and increased GSH level in the liver when compared with MSG only. In conclusion, aqueous extract of A. sceptrum may have beneficial effect in MSG induced toxicity in rats by improving GSH level as well as liver function markers in a dose dependent manner.

Resveratrol attenuates doxorubicin-induced toxicity during in vitro culture of mouse-isolated preantral follicles.

The aims of this study were to evaluate the doxorubicin concentration that induces toxic effects on in vitro culture of isolated mouse secondary follicles and to investigate whether resveratrol can inhibit or reduce this toxicity. Secondary follicles were isolated and cultured for 12 days in control medium (α-MEM+) or in α-MEM+ supplemented with doxorubicin (0.1 µg/ml) or different concentrations of resveratrol (0.5, 2, or 5 µM) associated with doxorubicin (0.1 µg/ml) (experiment 1). For experiment 2, follicles were cultured in α-MEM+ alone or supplemented with doxorubicin (0.3 µg/ml) or different concentrations of resveratrol (5 or 10 µM) associated or not with doxorubicin (0.3 µg/ml) (experiment 2). The endpoints analyzed were morphology (survival), antrum formation, follicular diameter, mitochondrial activity, glutathione (GSH) levels and DNA fragmentation. In the first experiment, doxorubicin (0.1 µg/ml) maintained survival and antrum formation similar to the control, while 5 µM resveratrol showed increased parameters, maintained mitochondrial activity and increased GSH levels compared to the control. In the second experiment, doxorubicin (0.3 µg/ml) reduced survival, antrum formation and follicular diameter compared to the control. Resveratrol at a concentration of 10 µM attenuated the damage caused by doxorubicin by improving follicular survival and did not present DNA fragmentation. In conclusion, supplementation of the in vitro culture medium with 0.3 µg/ml doxorubicin reduced the survival and impaired the development of mouse-isolated preantral follicles. Resveratrol at 10 µM reduced doxorubicin-induced follicular atresia, without DNA fragmentation in the follicles.