Decreased Superoxide Dismutase Activity Research Articles

16S rRNA methyltransferase KsgA contributes to oxidative stress and antibiotic resistance in Pseudomonas aeruginosa

Ribosomal RNA (rRNA) modifications are involved in multiple biological processes. KsgA is a 16S rRNA adenine dimethyltransferase that methylates at the adenines 1518 and 1519 (A1518/1519) positions, which are located near the ribosome decoding center. These methylations are conserved and important for ribosome biogenesis and protein translation. In this study, we demonstrated the absence of A1518/1519 methylation in the 16S rRNA of a Pseudomonas aeruginosa ksgA mutant. Biolog phenotypic microarrays were used to screen the phenotypes of the ksgA mutant against various antimicrobial agents. The loss of ksgA led to increased sensitivity to menadione, a superoxide generator, which was, at least in part, attributed to decreased in a superoxide dismutase (SOD) activity. Interestingly, the decrease in SOD activity in the ksgA mutant was linked to a decrease in the SodM protein levels, but not the sodM mRNA levels. Furthermore, the ksgA mutant strain exhibited sensitivity to hygromycin B and tylosin antibiotics. The tylosin-sensitive phenotype was correlated with decreased transcriptional levels of tufA, tufB, and tsf, which encode elongation factors. Additionally, the ksgA mutant showed resistance to kasugamycin. Collectively, these findings highlight the role of KsgA in oxidative stress responses and antibiotic sensitivity in P. aeruginosa.

Tropisetron attenuates high glucose-induced oxidative stress and inflammation in ARPE-19 cells in vitro via regulating SIRT1/ROCK1 signaling.

Diabetic retinopathy (DR) is the leading cause of acquired blindness in diabetic patients. Tropisetron (TRO) exerts potent therapeutic effects against diabetic tissues. The present study aimed to investigate the effects of TRO on retinal injury under diabetic condition. Human retinal pigment epithelial cell line ARPE-19 was treated with high glucose (HG) for 48 h to mimic hyperglycemia-induced retinal damage and subsequently treated with multiple concentrations of TRO for therapeutic intervention. Cell viability and lactate dehydrogenase (LDH) release were detected to assess cell damage. The production of inflammatory cytokines and oxidative stress-related factors was evaluated by corresponding commercial kits. Cell apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The expression of inflammation-, apoptosis-, and SIRT1/ROCK1-related proteins was examined using western blot analysis. Additionally, ARPE-19 cells were transfected with over-express ROCK1 (Ov-ROCK1) or pretreatment with SIRT1 inhibitor EX527 to perform the rescue experiments. TRO alleviated cell damage in HG-induced ARPE-19 cells through elevating cell viability and reducing LDH release. HG-caused excessive production of TNF-α, IL-1β and IL-6, ROS, malondialdehyde and decreased superoxide dismutase activity were partly inhibited by TRO treatment. HG-induced cell apoptosis, accompanied with the upregulation of proapoptotic proteins and the downregulation of antiapoptotic proteins, was hindered by TRO treatment. HG led to the loss of SIRT1 and an elevation of ROCK1 in ARPE-19 cells, which was reversed following TRO treatment. Furthermore, pretreatment with EX527 or transfected with Ov-ROCK1 partially abolished the protective role of TRO against inflammation, oxidative stress and cell apoptosis in HG-challenged ARPE-19 cells. TRO exerted a protective role against HG-caused ARPE-19 cells inflammation, oxidative stress and cell apoptosis by regulating SIRT1/ROCK1 axis, suggesting that TRO might be therapeutic agent for alleviating retinal pigment epithelial cell damage in DR.

Stem extract from Costus afer (Bush cane) prevents ethanol-induced neuronal degeneration in mice via an antioxidant-inflammatory pathway

BackgroundExcessive alcohol consumption is associated with memory impairment and can lead to Alzheimer's disease-like dementia, contributing to the rising prevalence of dementia worldwide. Costus afer (Bush cane) is a medicinal plant widely used in traditional African medicine for its anti-inflammatory, antioxidant, and neuroprotective properties. It is commonly employed to treat various ailments, including inflammatory diseases, respiratory conditions, and gastrointestinal disorders. PurposeGiven its traditional use in the treatment of kyphosis (hunchback) which is implicated in cerebral palsy and degenerative disease of the spine, we explored its potential neuroprotective effects against ethanol-induced neuronal degeneration, in this research, we examined the potential protective impacts on memory and neurology afforded by the aqueous stem extract derived from C. afer in mice subjected to ethanol exposure. MethodsForty-five male Swiss mice weighing 22–35 g were divided into five groups (n = 9): control (treated with distilled water orally), memory-impaired (treated with ethanol at 5 g/kg orally), and three groups treated with ethanol followed by administration of C. afer at doses of 100 mg/kg, 200 mg/kg, and 500 mg/kg respectively. All animals were provided unrestricted access to both food and water throughout the duration of the study. Memory impairment was assessed after 28 days using the T-maze spontaneous alternation test. Subsequently, spectrophotometry, ELISA, and histomorphometry were employed to evaluate indicators of neuronal inflammation, oxidative stress linked to inflammation, and degenerative changes were assessed in the hippocampus, prefrontal cortex, and cerebellum. ResultsEthanol administration led to a notable (p < 0.01) decline in neurobehavioral function, as evidenced by reduced spontaneous alternation behavior, which was mitigated by C. afer treatment, leading to increased percentage alternation. Furthermore, ethanol administration altered endogenous antioxidant levels and pro-inflammatory mediators, resulting in elevated lipid peroxidation, nitrite, tumor necrosis factor-alpha, interleukin-6, and decreased superoxide dismutase activity, promoting neuronal degeneration in the mice brains. However, treatment with C. afer at doses of 100 mg/kg, 200 mg/kg, and 500 mg/kg substantially (p < 0.05) attenuated oxidoinflammatory stress by reducing levels of MDA, NO-2, TNF-α, IL-6, while upregulating SOD activity, thereby preserving neuronal integrity in the hippocampus, prefrontal cortex, and cerebellum. ConclusionThese findings suggest that C. afer mitigates the progression of memory impairment induced by ethanol through mechanisms involving the suppression of oxidoinflammatory stress facilitators and inhibition of cortico-hippocampal and cerebellar neuronal degeneration in murine subjects.

Impact of Pterostilbene on Lens Epithelial Cells from Cataract Model Rats

Lens epithelial cell (lEC) membrane is one of the pathological process of cataract. Sandalwood stilbene is a kind of non-flavonoid polyphenol extracted from blueberries, grapes and other berries. It is considered as a natural antioxidant through various related mechanisms. This study was to investigate the effect and mechanism of Rosewood astragalus on lEC in oxidative cataract rats, and to provide evidence for clinical cataract treatment. Grouping method: normal control group, model group (H2O2 induced cataract) and Zitan astragalus group. Lens turbidity was observed, LECs was isolated and cultured. MTT assay was used to detect LECs proliferation and Caspase-3 activity was used to detect LECs apoptosis. The expression of NF-κB pathway was analyzed. The activities of superoxide dismutase (SOD), reactive oxygen species (ROS) were detected. The results showed that H2O2 significantly increased lens turbidity, enhanced Caspase-3 activity, inhibited LECs proliferation, increased NF-κB pathway expression, increased ROS activity, and decreased SOD activity (P &lt;0.05). Dansandalus stilbene had the effects of inhibiting NF-κB pathway expression, promoting LECs proliferation, decreasing Caspase-3 activity, decreasing ROS production and increasing SOD activity (P &lt; 0.05). In this study, it is suggested that Rosewood stilbene delaying the oxidation of traumatic cataract by anti-oxidation and apoptosis of LECs, and regulating cell proliferation, inhibiting the expression of NF-κB.

Impact of levetiracetam and ethanol on memory, selected neurotransmitter levels, oxidative stress parameters, and essential elements in rats.

Ethanol disrupts brain activity and memory. There is evidence supporting the beneficial effect of levetiracetam on alcohol consumption. Therefore, the aim of the study was to examine whether levetiracetam has a protective activity against ethanol-induced memory impairment, alterations in selected neurotransmission activities, oxidative stress, and selected essential elements in rats. The rats were given levetiracetam (300mg/kg b.w. po) with ethanol for three weeks prior to behavioral tests. Spatial memory was tested using the Morris water maze, while recognition memory was evaluated using the Novel object recognition test. The GABA and glutamate concentration was determined in three rat brain regions (cerebellum, hippocampus, and cerebral cortex). Serum oxidative stress parameters and selected essential elements concentration (Cu, Mn, Zn, Fe, Mg) in the rat brain were analyzed. Levetiracetam administered with ethanol improved spatial memory, but did not affect abstinence-induced impairment. The drug also decreased ethanol-induced long-term recognition memory impairment. No alterations in glutamate levels were observed. GABA levels were elevated by levetiracetam in the cerebral cortex and by ethanol in the cerebellum. Ethanol increased catalase activity (CAT) and decreased superoxide dismutase activity (SOD) in the serum. Levetiracetam significantly increased the activity of SOD. Alcohol disrupted the levels of trace elements (Mn, Zn, Mg) in the rat brain. Additionally, levetiracetam alone increased Mg, Fe, and Cu concentrations while all animals receiving the drug also had significantly lower concentrations of Zn. Levetiracetam had differential effects against ethanol-induced impairments. These findings could have important implications for future levetiracetam treatment in patients.

The effect of eight-week resistance training on oxidative stress in isoproterenol-induced myocardial infarction in rats

IntroductionAlthough reliable new evidence has identified several advantages of resistance training (ResEx) on cardiac performance, the role of this type of training in protecting the myocardium against ischemia-reperfusion (IR) injury is not clear. The aim of this study was to investigate the effect of resistance training on cardioprotection versus IR-induced injury.Material and methods60-day-old male Wistar rats (n = 24), weighing 220–240 g, were divided into four groups: Resistance Training (ResEx), Isoproterenol (ISO), Resistance Training + Isoproterenol (ResEx + ISO), and control groups (n = 6 for each). Trained rats performed exercise in a squat-training apparatus (8–12 repetitions/set, eight sets/day, and 5 days/week for 8 weeks). After the last training session, all the rats were sacrificed with ketamine xylazine injection. The heart of rats was removed from the body and washed quickly with cold PBS, immediately put in liquid nitrogen, and stored at –70°C. Superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) activity was measured.ResultsInduction of ischemia decreased SOD and CAT activity but had no effect on the activity of GPX. Eight weeks of resistance training significantly increased activity of SOD and CAT compared to the ISO group.ConclusionsThe results of the present research demonstrated that ischemia induced by isoproterenol injection during 8 weeks of resistance training did not lead to a decrease in SOD activity and prevented the reduction of CAT activity.

The effect of supplementing freezing extender with Mn2+-, Zn2+- or Cu2+-nanosuccinate on select post-thaw characteristics of ram semen

The effects of Mn2+-, Zn2+- or Cu2+-nanosuccinate added to freezing extender on select post-thaw semen characteristics were determined in six Texel rams (aged 2–4 years) during seasonal anestrus (April-May). Ejaculates (n = 6 per ram) collected into an artificial vagina were divided into ten isovolumetric fractions each. Semen was diluted in lactose-yolk-tris-citrate-glycerin medium and nanosuccinates (Mn2+- and Zn2+-nanosuccinate: 0.0 (control), 2.5, 5.0 and 7.5 μg/l; Cu2+-nanosuccinate: 0.0 (control), 1.25, 2.5 and 3.75 μg/l) were added to semen extender. Extended semen was loaded into 0.25-ml straws and frozen in liquid nitrogen. After thawing, sperm motility parameters were determined with computer assisted semen analysis (CASA), and the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) was measured with a spectrophotometric technique. The addition of 5.0 μg/l of Mn2+- and Zn2+-nanosuccinate significantly increased the sperm progressive motility and both 2.5 and 5.0 μg/l improved sperm motion kinetics. Further, both nanosuccinates at a dose of 5.0 μg/l significantly decreased SOD activity and stimulated an increase in GPx and CAT activity in semen samples. Alternatively, the addition of Cu2+-nanosuccinate (highest dose) significantly reduced the progressive motility and velocity of ram spermatozoa, increased the percentage of sperm with acrosomal/head defects and seminal SOD activity, and depressed CAT (highest dose) and GPx (all doses) activity. In summary, the addition of Mn2+- and Zn2+-nanosuccinate to semen extender had beneficial effects on sperm motility/motion kinetics and structural integrity, whereas Cu2+-nanosuccinate generally had debilitating effects on the post-thaw semen characteristics in rams.

MLR-1023 Improves Cognition Deficiency and Oxidative Stress in Lipopolysaccharide-Induced Mice Model of Alzheimer’s Disease: Role of PPAR-gamma Receptors and NO-cGMP-KATP Channels Pathway

Background: This study investigates the effects of MLR-1023 on cognitive deficiency and oxidative stress in a lipopolysaccharide (LPS)-induced mouse model. Objectives: The role of PPAR-gamma receptors and the NO- cyclic GMP (cGMP)-KATP channel pathway were examined to identify the likely mechanisms. Methods: The model was established by LPS injection. Behavioral assays included shuttle box and Y-maze tests. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were then measured in hippocampal tissue. To explore the probable mechanisms, the mice were pre-treated with agonists and antagonists 15 minutes before MLR-1023 (20 - 40 mg/kg, i.p.) administration. Results: Lipopolysaccharide increased the initial latency (IL) time, while MLR-1023 (40 mg) reduced it. Administration of L-NAME, methylene blue, and glibenclamide with MLR-1023 increased IL duration, while L-arginine, sildenafil, and diazoxide reduced it. Lipopolysaccharide reduced the duration of step-through latency (STL), whereas MLR-1023 increased it. L-NAME, methylene blue, and glibenclamide with MLR-1023 reduced STL duration, but L-arginine, sildenafil, and diazoxide increased it. The spontaneous alternation index decreased with LPS, while MLR-1023 increased it. L-NAME, methylene blue, glibenclamide, and GW9662 decreased this index, whereas L-arginine, sildenafil, diazoxide, and pioglitazone increased it. Lipopolysaccharide increased MDA concentration, while MLR-1023 decreased it. L-NAME, methylene blue, and glibenclamide increased MDA concentration, while L-arginine, diazoxide, and pioglitazone decreased it. Lipopolysaccharide reduced SOD activity, which was improved by MLR-1023. L-NAME, methylene blue, glibenclamide, and GW9662 decreased SOD activity, while sildenafil and pioglitazone increased it. Conclusions: MLR-1023 can improve LPS-induced learning-memory impairment and oxidative stress. The KATP/cGMP/NO pathway and PPARγ receptors are involved in this effect.

Evaluation of effects of bisphenol analogs AF, S, and F on viability, proliferation, production of selected cancer-related factors, and expression of selected transcripts in Caov-3 human ovarian epithelial cell line

Bisphenol A (BPA) has been a substantial additive in plastics until the reports on its adverse effects have led to its restrictions and replacement. Monitoring studies document the increasing occurrence of bisphenol analogs, however, data on their effects and risks is still insufficient. Based on the indications that BPA might contribute to ovarian cancer pathogenesis, we examined effects of the analogs AF (BPAF), S (BPS) and F (BPF) (10−9–10−4 M) on the Caov-3 epithelial cancer cells, including the impact on cell viability, proliferation, oxidative stress, and production and expression of several factors and genes related to ovarian cancer. At environmentally relevant doses, bisphenols did not exert significant effects. At the highest concentration, BPAF caused varied alterations, including decreased cell viability and proliferation, caspase activation, down-regulation of PCNA and BIRC5, elevation of IL8, VEGFA, MYC, PTGS2 and ABCB1 expressions. Only BPA (10−4 M) increased IL-6, IL-8 and VEGFA output by the Caov-3 cells. Each bisphenol induced generation of reactive oxygen species and decreased superoxide dismutase activity at the highest concentration. Although the effects were observed only in the supraphysiological doses, the results indicate that certain bisphenol analogs might affect several ovarian cancer cell characteristics and merit further investigation.

In Vitro Protective Effect of Pea-Derived Peptides (PPs) via the Keap1/Nrf2 Signaling Pathway on Alpha-Gliadin-Sensitizing Peptide Induced Cacao-2 Cells.

Celiac disease (CD) is an allergic intestinal disease caused mainly by gliadin in wheat, which is widespread in the population and currently lacks effective treatment. α-Gliadin peptides cause cellular damage by substantially increasing cellular reactive oxygen species (ROS) levels. This study investigates the protective effect of 11 pea-derived peptides (PPs) on ɑ-gliadin peptide (P31-43) treated Caco-2 cells. Results show that cells treated with PP2, PP5, and PP6 peptides significantly reduce the cell mortality caused by P31-43. Three PPs significantly reduce the P31-43-induced decrease in ROS levels to control levels, and there is no difference between them and the vitamin C (Vc) group. The results in terms of antioxidant-related enzymes show that PPs significantly decrease superoxide dismutase activity (SOD), glutathione reductases (GR), and glutathione (GSH)/oxidized glutathione (GSSG) levels, thus significantly enhancing the antioxidant level of cells. By studying the key proteins of the Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor 2 (Nrf2) pathway, it is found that PPs activate the Keap1/Nrf2 signaling pathway. The study finds that peptides from peas can effectively alleviate ɑ-gliadin peptide-induced cell damage. The discovery of these food-derived peptides provides novel potential solutions for the prevention and treatment of CD.

Exploring the Therapeutic Potential of Sodium Hydrosulfide in Alleviating Oxidative Stress and Ovarian Dysfunction in a Rat Model of Polycystic Ovary Syndrome.

Oxidative stress is known to play a key role in the occurrence of polycystic ovary syndrome (PCOS) as the most common cause of anovulatory infertility. The purpose of the current study was to investigate whether diminished activity of ovarian enzymes responsible for hydrogen sulfide (H2S) production, cystathionine β-synthase (CBS), and cystathionine γ-lyase (CSE) contributes to oxidative stress in PCOS. The study also explored whether administration of sodium hydrosulfide (NaSH), an H2S donor, could ameliorate PCOS symptoms by reducing oxidative stress. The total eighteen rats were randomly assigned into three groups (n=6): control, PCOS, and PCOS+NaSH. PCOS was induced by intramuscular injection of estradiol valerate to induce PCOS in the PCOS and PCOS+NaSH groups. The PCOS+NaSH group received 30 μmol/L of NaSH in drinking water for 27 days after PCOS induction. Ovarian tissue samples were analyzed for oxidative stress indices including malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Additional analyses measured H2S levels, CBS, and CSE activity. PCOS induction led to a significant decrease in SOD activity, H2S levels, and CBS and CSE activity, accompanied by a significant increase in MDA levels (p<0.0001). Furthermore, PCOS caused severe histological alterations in the ovaries. However, administration of NaSH effectively restored all measured parameters to pre-PCOS induction levels (p<0.0001). This study showed that the decrease in the activity of H2S-producing enzymes and H2S levels may contribute to oxidative stress in PCOS. Therefore, administration of NaSH as a H2S donor can be considered as a potential therapeutic strategy for PCOS patients.

Alleviating Acute Lung Injury Induced by Lipopolysaccharide: Dayuan Yin Suppresses Inflammation and Oxidative Stress in Elderly Male Rats.

The occurrence of acute lung injury (ALI) caused by lipopolysaccharide (LPS) is prevalent and perilous among older individuals. Inflammation and oxidative stress are vital factors in the progression of ALI in this population. Dayuan Yin (DYY) is a classic Chinese herbal formula used for treating pulmonary diseases. Therefore，this situation can be well simulated by selecting suitable aged rats and induced by LPS, which is helpful to evaluate the role of DYY. The objective of this study is to assess the therapeutic efficacy of DYY in reducing pulmonary inflammation and oxidative stress injury in aged rats induced by LPS. In elderly male Sprague Dawley (SD) rats, the ALI model was induced by injecting LPS into the peritoneal cavity. The therapeutic effect of the DYY group was evaluated after 3 days of oral administration. Lung tissue damage was assessed using hematoxylin-eosin staining and the lung wet/dry (W/D) ratio. Inflammatory reaction in lung tissue was analyzed by counting inflammatory agents, measuring total protein (TP), and examining the concentration of inflammatory components in bronchoalveolar lavage fluid (BALF). Lung oxidative stress was assessed by measuring malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), and superoxide dismutase (SOD) levels in BALF. The impact of DYY on the phosphorylation of PI3K, AKT, and NF-κBp65 protein was analyzed using Western Blot (WB). The administration of DYY exhibited a dose-dependent reduction in the severity of lung injury caused by LPS, leading to a reversal of the LPS-induced lung W/D ratio. Furthermore, DYY treatment resulted in decreased levels of leukocytes, eosinophils, neutrophils, macrophages, lymphocytes, and total protein in BALF. Additionally, DYY significantly inhibited the upregulation of Interleukin -6, Interleukin -10, and Interleukin -1β (IL-6, IL-10, IL-1β) as well as Tumor necrosis factor-α(TNF-α) induced by LPS (P<0.01). The lungs experienced oxidative stress due to LPS, leading to the production of MDA and iNOS, as well as a decrease in SOD activity. DYY reduced oxidative stress in the lungs and inhibited the activation of p-PI3K, p-Akt, and p-NF-κBp65, with a greater effect at higher doses. In a dose-dependent manner, DYY suppresses the inflammatory response and oxidative stress in the lung tissue of elderly rats, thereby reducing ALI caused by LPS. This effect may be attributed to the inhibition of the PI3K/AKT/NF-κB pathway activation.

Serum Total Superoxide Dismutase Activity as a Predictive Factor in Patients with Hepatocellular Carcinoma

Objectives: This study aimed to determine the cutoff value for diagnosis and predict mortality in hepatocellular carcinoma (HCC) based on serum total superoxide dismutase (SOD) activity. Methods: A retrospective case-control study of the SOD Model was conducted using data from a single-center dataset at Shandong Provincial Hospital Affiliated with Shandong First Medical University, China. Serum total SOD activity was analyzed in HCC patients (n = 124) and control subjects (n = 117). Receiver operating characteristic (ROC) curves were used to determine cutoff values of serum total SOD activity for HCC diagnosis. Overall survival (OS) was assessed using the Kaplan-Meier method. Results: In the model groups, the cutoff level of total SOD activity for HCC was 169.2 U/mL (sensitivity: 87.23%, specificity: 91.95%), while for HCC [alpha fetoprotein (AFP) &lt; 20 ng/mL], it was 173.4 U/mL (sensitivity: 86.79%, specificity: 88.51%). Additionally, in the validation groups, the true positive rate, true negative rate, and accuracy rate were all above 90%. Based on the cutoff value of SOD, HCC patients were assigned to an H-SOD and L-SOD group depending on their serum total SOD activity at admission before operation. The 5-year OS rate of the H-SOD group was 75.00%, and that of the L-SOD group was 36.59% in HCC patients (P = 0.0245). With a decrease in SOD activity, serum levels of Zn (t = 3.890, P = 0.0003) and Se (t = 7.694, P &lt; 0.0001) were also significantly decreased and positively correlated with SOD activity (both P &lt; 0.05) in HCC patients. Conclusions: Low serum total SOD activity may also be a risk factor for HCC. The decrease of SOD activity in HCC patients was partly related to a lack of Zn and Se.

Biochemical state of brain-liver axis of rats under restraint-induced stress and 2-oxoglutarate impact

Environmental factors play a significant role in affecting the overall health of organisms, with stress being a notable contributor. The process of urbanization and globalization in modern society introduces additional stressors, exacerbating population health issues. Consequently, there is a need for thorough examination, analysis, and exploration of strategies to mitigate the adverse effects of stress. 2-Oxoglutarate, an essential intracellular metabolite and mediator with metabolite trophic properties, emerges as a promising candidate for intervention. In this study, we aimed to evaluate the combined impact of restraint-induced stress and 2-oxoglutarate on the oxidative-reducing balance, antioxidant system effectiveness, and the functional status of the liver and brain in rats. Restraint-induced stress was found to elevate oxidative stress levels, as evidenced by increased concentrations of malonic dialdehyde and oxidative-modified proteins, particularly in the brain. Additionally, signs of lactic acidosis were observed in the liver, indicating physiological changes in response to stress. Furthermore, restraint-induced stress significantly altered bioenergy components, with decreased superoxide dismutase activity and increased cytochrome C concentration, potentially indicating mitochondrial dysfunction and increased membrane permeability. The incorporation of a 2% solution of 2-oxoglutarate into the diet demonstrated a reduction in malonic dialdehyde and carbonylated protein formation, leading to more effective restoration of oxidative-reducing balance in the brain compared to the liver. Additionally, normalization of the lactate/pyruvate concentration ratio and decreased lactate dehydrogenase activity, alongside elevated alanine aminotransferase levels, suggested a decrease in oxidative stress in the liver. Moreover, exogenous 2-oxoglutarate exhibited a positive effect on superoxide dismutase activity and cytochrome C concentration, indicating a reduction in oxidative tension in the liver and progressive mitochondrial function recovery. Based on these findings, exogenous 2-oxoglutarate emerges as a promising metabolitotrope and adaptogen for managing oxidative stress and improving mitochondrial function.

The effects of cadmium on selected oxidative stress parameters and the content of photosynthetic pigments in cucumber Cucumis sativus L.

BackgroundEnvironmental pollution by cadmium (Cd) is currently a common problem in many countries, especially in highly industrialised areas. Cd present in the soil can be absorbed by plants through the root system. AimThe aim of the present study was to investigate the effects of cadmium on the metabolic activity of cucumber plants (Cucumis sativus L.) and the accumulation and distribution of Cd in the organs of the plants. MethodsCucumber seeds (3 g) were exposed to 0.76, 1.58 or 4.17 mg Cd/L (applied as CdCl2 solutions). The activity of selected antioxidant enzymes - glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT), lipid peroxidation and the content of photosynthetic pigments were determined in 6-week-old cucumber plants. In addition, intake of Cd has been determined by flame atomic absorption spectrometry (F-AAS). ResultsThe results show that the applied cadmium concentrations affected the activity of antioxidant enzymes. An increase in CAT activity and a decrease in SOD activity were observed in all cucumber organs analysed. GSH-Px activity increased in the roots and stems. Surprisingly, GSH-Px activity decreased in the leaves. The level of lipid peroxidation was usually unchanged (the only one statistically significant change was a decrease in the concentration of malondialdehyde in the leaves which was observed after exposure to the highest Cd concentration). The applied Cd concentrations had no effect on the content of photosynthetic pigments. The highest cadmium content was found in the roots of cucumber plants. Cd tends to accumulate in the roots and a small amount was translocated to the stems and leaves, which was confirmed with the translocation factor (TF). ConclusionsThe results indicate that the range of cadmium concentrations used, corresponding to the level of environmental pollution recorded in Europe, effectively activates the antioxidant enzyme system, without intensifying lipid peroxidation or reducing the content of photosynthetic pigments.

Protective effect of oxytocin on vincristine-induced gastrointestinal dysmotility in mice.

Aims: Vincristine (VCR), an antineoplastic drug, induces peripheral neuropathy characterized by nerve damage, limiting its use and reducing the quality of life of patients. VCR causes myenteric neuron damage, inhibits gastrointestinal motility, and results in constipation or paralytic ileus in patients. Oxytocin (OT) is an endogenous neuropeptide produced by the enteric nerve system, which regulates gastrointestinal motility and exerts neuroprotective effects. This study aimed to investigate whether OT can improve VCR-induced gastrointestinal dysmotility and evaluate the underlying mechanism. Methods: Mice were injected either with saline or VCR (0.1mg/kg/d, i. p.) for 14 days, and OT (0.1mg/kg/d, i.p.) was applied 1h before each VCR injection. Gastrointestinal transit and the contractile activity of the isolated colonic segments were assessed. The concentration of OT in plasma was measured using ELISA. Immunofluorescence staining was performed to analyze myenteric neurons and reactive oxygen species (ROS) levels. Furthermore, the indicators of oxidative stress were detected. The protein expressions of Nrf2, ERK1/2, P-ERK1/2, p38, and P-p38 in the colon were tested using Western blot. Results: VCR reduced gastrointestinal transit and the responses of isolated colonic segments to electrical field stimulation and decreased the amount of neurons. Furthermore, VCR reduced neuronal nitric oxide synthase and choline acetyltransferase immunopositive neurons in the colonic myenteric nerve plexus. VCR increased the concentration of OT in plasma. Exogenous OT pretreatment ameliorated the inhibition of gastrointestinal motility and the injury of myenteric neurons caused by VCR. OT pretreatment also prevented the decrease of superoxide dismutase activity, glutathione content, total antioxidative capacity, and Nrf2 expression, the increase of ROS levels, and the phosphorylation of ERK1/2 and p38 MAPK following VCR treatment. Conclusion: Our results suggest that OT pretreatment can protect enteric neurons from VCR-induced injury by inhibiting oxidative stress and MAPK pathways (ERK1/2, p38). This may be the underlying mechanism by which it alleviates gastrointestinal dysmotility.

Effect of light and noise pollution on oxidative stress and proximate composition in Dreissena polymorpha

In this study, it was aimed to determine the effect of sound and light pollution on Zebra mussel (Dreissena polymorpha) by biomarker and nutritional composition. For this purpose, an experimental design was carried out in laboratory conditions where the model was exposed to live sound, light, and combined sound + light parameters for 30 min every hour over 96 h. Changes in the biomarkers superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, as well as glutathione (GSH) and thiobarbituric acid (TBARS) levels, were assessed in the model organism exposed to sound, light, and sound + light pollution. The changes in protein and fat amounts were determined. When the changes in biomarkers were examined statistically compared to the control, there was no significant decrease in SOD activity (p < 0.05), a significant increase in CAT activity in sound and sound+light, but a significant decrease in light (p < 0.05), no significant difference in GPx activity (p > 0.05). It was determined that there was a significant increase in GSH and TBARS levels in all three parameters. Significant changes were also observed in the proximate composition. As a result, exposure to sound, light and sound+light pollution caused an increase in oxidative damage and decreases in protein and lipid composition were detected.

Aristolochic acid induces acute kidney injury through ferroptosis.

Aristolochic acid (AA)-induced acute kidney injury (AKI) presents with progressive decline in renal function and rapid progression to end-stage renal disease. Among the multiple mechanisms identified in AKI, ferroptosis has been shown to be involved in various forms of AKI. But few studies have elucidated the role of ferroptosis in AA-induced AKI. In this study, we investigated the role of ferroptosis in AA-induced acute renal tubular injury in vivo and in vitro. Mice with acute aristolochic acid nephropathy showed increased malondialdehyde levels, aggravated lipid peroxidation, decreased superoxide dismutase activity, and glutathione depletion. The expression of glutathione peroxidase 4 was decreased and the expression of acyl-CoA synthetase long-chain family member 4 was increased. Inhibition of ferroptosis by ferrostatin-1 significantly improved the renal function, reduced histopathological lesions, partially alleviated lipid peroxidation, and restored the antioxidant capacity. In vitro studies also revealed that AA significantly reduced cell viability, induced reactive oxygen species production, increased intracellular iron level and decreased ferroptosis-related protein expression. Inhibition of ferroptosis significantly increased cell viability and attenuated AA-induced renal tubular epithelial cell injury. It is suggested that ferroptosis plays an important role in AA-induced acute tubular injury. And inhibition of ferroptosis may exert renoprotective effects possibly by preventing lipid peroxidation, restoring the antioxidant activity or regulating iron metabolism.

Nesfatin-1 alleviates hyperoxia-induced bronchopulmonary dysplasia (BPD) via the nuclear factor-κB (NF-κB) p65 signaling pathway.

Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease in newborns, which severely influences the health of infants and lacks effective clinical treatment strategies. The pathogenesis of BPD is correlated to enhanced inflammation and activated oxidative stress (OS). The application of antioxidants and anti-inflammatory treatment could be hot spots for BPD treatment. Nesfatin-1, a peptide with a suppressive property against inflammation, was tested herein for its potential therapeutic value in BPD. Neonatal SD rats were stimulated with hyperoxia, followed by being intraperitoneally administered with 20 μg/kg/day Nesfatin-1 for 2 weeks. Decreased RAC value in lung tissues, increased wet weight/dry weight (W/D) pulmonary ratio and bronchoalveolar lavage fluid (BALF) proteins, elevated cytokine release in BALF, increased malondialdehyde (MDA) content, and declined superoxide dismutase (SOD) activity were observed in BPD rats, all of which were sharply mitigated by Nesfatin-1. Rat epithelial type II cells (AECIIs) were handled with hyperoxia, and then cultured with 1 and 10 nM Nesfatin-1. Reduced cell viability, elevated lactate dehydrogenase production, elevated cytokine secretion, elevated MDA content, and decreased SOD activity were observed in hyperoxia-handled AECIIs, all of which were markedly alleviated by Nesfatin-1. Furthermore, activated nuclear factor-κB (NF-κB) signaling observed in both BPD rats and hyperoxia-handled AECIIs were notably repressed by Nesfatin-1. Collectively, Nesfatin-1 alleviated hyperoxia-triggered BPD by repressing inflammation and OS via the NF-κB signaling pathway.

Diazoxide attenuates DOX-induced cardiotoxicity in cultured rat myocytes.

Doxorubicin (DOX)-induced cardiotoxicity is a well known clinical problem, and many investigations have been made of its possible amelioration. We have investigated whether diazoxide (DIA), an agonist at mitochondrial ATP-sensitive potassium channels (mitoKATP), could reverse DOX-induced apoptotic myocardial cell loss, in cultured rat cardiomyocytes. The role of certain proteins in this pathway was also studied. The rat cardiomyocyte cell line (H9c2) was treated with DOX, and also co-treated with DOX and DIA, for 24 h. Distribution of actin filaments, mitochondrial membrane potential, superoxide dismutase (SOD) activity, total oxidant and antioxidant status (TOS and TAS, respectively), and some protein expressions, were assessed. DOX significantly decreased SOD activity, increased ERK1/2 protein levels, and depolarised the mitochondrial membrane, while DIA co-treatment inhibited such changes. DIA co-treatment ameliorated DOX-induced cytoskeletal changes via F-actin distribution and mitoKATP structure. Co-treatment also decreased ERK1/2 and cytochrome c protein levels. Cardiomyocyte loss due to oxidative stress-mediated apoptosis is a key event in DOX-induced cytotoxicity. DIA had protective effects on DOX-induced cardiotoxicity, via mitoKATP integrity, especially with elevated SUR2A levels; but also by a cascade including SOD/AMPK/ERK1/2. Therefore, DIA may be considered a candidate agent for protecting cardiomyocytes against DOX chemotherapy.