The antioxidant activity and metabolomic analysis of the supernatant of Streptococcus alactolyticus strain FGM.

Strain-specific probiotics can present antioxidant activity and reduce damage caused by oxidation. Streptococcus alactolyticus strain FGM (S. alactolyticus strain FGM) isolated from the chicken cecum shows potential probiotic properties which have been previously demonstrated. However, the antioxidant properties of S. alactolyticus strain FGM remain unknown. In this view, cell-free supernatant (CFS), intact cells (IC) and intracellular extracts (CFE) of strain FGM and 3 strains of Lactobacillus (LAB) were prepared, and their scavenging capacities against DPPH, hydroxyl radicals and linoleic acid peroxidation inhibitory were compared in this study. The effects of strain FGM cell-free supernatant (FCFS) on NO production, activity of SOD and GSH-Px in RAW264.7 cells and LPS-induced RAW264.7 cells were analyzed. The metabolites in the supernatant were quantitated by N300 Quantitative Metabolome. It was shown that the physicochemical characteristics of CFS to scavenge DPPH, hydroxyl radicals, and linoleic acid peroxidation inhibitory were significantly stronger than that of IC and CFE in the strain FGM (P < 0.05), respectively 87.12% ± 1.62, 45.03% ± 1.27, 15.63% ± 1.34. FCFS had a promotional effect on RAW264.7 cells, and significantly elevated SOD and GSH-Px activities in RAW264.7 cells. 25 µL FCFS significantly promoted the proliferation of RAW264.7 cells induced by LPS, increased the activities of SOD and GSH-PX, and decreased the release of NO. Furthermore, among the differential metabolites of FCFS quantified by N300, 12 metabolites were significantly up-regulated, including lactic acid, indole lactic acid, linoleic acid, pyruvic acid etc., many of which are known with antioxidant properties. In conclusion, FCFS had good antioxidant properties and activity, which can be attributed to metabolites produced from strain FGM fermentation. It was further confirmed that S. alactolyticus strain FGM and its postbiotic have potential probiotic properties and bright application prospects in livestock and poultry breeding.

Beta hydroxybutyrate induces lung cancer cell death, mitochondrial impairment and oxidative stress in a long term glucose-restricted condition.

BACKGROUND: Metabolic plasticity gives cancer cells the ability to shift between signaling pathways to facilitate their growth and survival. This study investigates the role of glucose deprivation in the presence and absence of beta-hydroxybutyrate (BHB) in growth, death, oxidative stress and the stemness features of lung cancer cells. METHODS AND RESULTS: A549 cells were exposed to various glucose conditions, both with and without beta-hydroxybutyrate (BHB), to evaluate their effects on apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS) levels using flow cytometry, and the expression of CD133, CD44, SOX-9, and ß-Catenin through Quantitative PCR. The activity of superoxide dismutase, glutathione peroxidase, and malondialdehyde was assessed using colorimetric assays. Treatment with therapeutic doses of BHB triggered apoptosis in A549 cells, particularly in cells adapted to glucose deprivation. The elevated ROS levels, combined with reduced levels of SOD and GPx, indicate that oxidative stress contributes to the cell arrest induced by BHB. Notably, BHB treatment under glucose-restricted conditions notably decreased CD133 expression, suggesting a potential inhibition of cell survival through the downregulation of CD133 levels. Additionally, the simultaneous decrease in mitochondrial membrane potential and increase in ROS levels indicate the potential for creating oxidative stress conditions to impede tumor cell growth in such environmental settings. CONCLUSION: The induced cell death, oxidative stress and mitochondria impairment beside attenuated levels of cancer stem cell markers following BHB administration emphasize on the distinctive role of metabolic plasticity of cancer cells and propose possible therapeutic approaches to control cancer cell growth through metabolic fuels.

Spilanthes filicaulis (Schumach. & Thonn.) C.D. Adams leaves protects against streptozotocin-induced diabetic nephropathy.

BACKGROUND AND OBJECTIVE: Diabetic neuropathy (DN) is a complex type of diabetes. The underlying cause of diabetic nephropathy remains unclear and may be due to a variety of pathological conditions resulting in kidney failure. This study examines the protective effect of the methanolic extract of Spilanthes filicaulis leaves (MESFL) in fructose-fed streptozotocin (STZ)-induced diabetic nephropathy and the associated pathway. METHODS: Twenty-five rats were equally divided randomly into five categories: Control (C), diabetic control, diabetic + metformin (100 mg/kg), diabetic + MESFL 150 mg/kg bw, and diabetic + MESFL 300 mg/kg bw. After 15 days, the rats were evaluated for fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, uric acid, serum creatinine, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (MDA). Gene expression levels of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element-binding (CREB), cFOS and the antiapoptotic protein Bcl-2 were examined. RESULTS: We observed that MESFL at 150 and 300 mg/kg bw significantly downregulated the protein expression of cAMP, PKA, CREB, and cFOS and upregulated the Bcl-2 gene, suggesting that the nephroprotective action of MESFL is due to the suppression of the cAMP/PKA/CREB/cFOS signaling pathway. In addition, MESFL increases SOD and CAT activities and GSH levels, reduces MDA levels, and reduces renal functional indices (ALP, urea, uric acid, and creatinine). CONCLUSION: Therefore, our results indicate that MESFL alleviates the development of diabetic nephropathy via suppression of the cAMP/PKA/CREB/cFOS pathways.

Competitive adsorption of microRNA-532-3p by circular RNA SOD2 activates Thioredoxin Interacting Protein/NLR family pyrin domain containing 3 pathway and promotes pyroptosis of non-alcoholic fatty hepatocytes.

OBJECTIVE: There is a growing body of evidence indicating that pyroptosis, a programmed cell death mechanism, plays a crucial role in the exacerbation of inflammation and fibrosis in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Circular RNAs (circRNAs), functioning as vital regulators within NAFLD, have been shown to mediate the process of cell pyroptosis. This study aims to elucidate the roles and mechanisms of circRNAs in NAFLD. METHODS: Utilizing a high-fat diet (HFD)-induced rat model for in vivo experimentation and hepatocytes treated with palmitic acid (PA) for in vitro models, we identified circular RNA SOD2 (circSOD2) as our circRNA of interest through analysis with the circMine database. The expression levels of associated genes and pyroptosis-related proteins were determined using quantitative real-time polymerase chain reaction and Western blotting, alongside immunohistochemistry. Serum liver function markers, cellular inflammatory cytokines, malondialdehyde, lactate dehydrogenase levels, and mitochondrial membrane potential, were assessed using enzyme-linked immunosorbent assay, standard assay kits, or JC-1 staining. Flow cytometry was employed to detect pyroptotic cells, and lipid deposition in liver tissues was observed via Oil Red O staining. The interactions between miR-532-3p/circSOD2 and miR-532-3p/Thioredoxin Interacting Protein (TXNIP) were validated through dual-luciferase reporter assays and RNA immunoprecipitation experiments. RESULTS: Our findings demonstrate that, in both in vivo and in vitro NAFLD models, there was an upregulation of circSOD2 and TXNIP, alongside a downregulation of miR-532-3p. Mechanistically, miR-532-3p directly bound to the 3'-UTR of TXNIP, thereby mediating inflammation and cell pyroptosis through targeting the TXNIP/NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathway. circSOD2 directly interacted with miR-532-3p, relieving the suppression on the TXNIP/NLRP3 signaling pathway. Functionally, the knockdown of circSOD2 or TXNIP improved hepatocyte pyroptosis; the deletion of miR-532-3p reversed the effects of circSOD2 knockdown, and the deletion of TXNIP reversed the effects of circSOD2 overexpression. Furthermore, the knockdown of circSOD2 significantly mitigated the progression of NAFLD in vivo. CONCLUSION: circSOD2 competitively sponges miR-532-3p to activate the TXNIP/NLRP3 inflammasome signaling pathway, promoting pyroptosis in NAFLD.

Exogenous Hemin enhances the antioxidant defense system of rice by regulating the AsA-GSH cycle under NaCl stress.

Abiotic stress caused by soil salinization remains a major global challenge that threatens and severely impacts crop growth, causing yield reduction worldwide. In this study, we aim to investigate the damage of salt stress on the leaf physiology of two varieties of rice (Huanghuazhan, HHZ, and Xiangliangyou900, XLY900) and the regulatory mechanism of Hemin to maintain seedling growth under the imposed stress. Rice leaves were sprayed with 5.0 µmol·L-1 Hemin or 25.0 µmol·L-1 ZnPP (Zinc protoporphyrin IX) at the three leaf and one heart stage, followed by an imposed salt stress treatment regime (50.0 mmol·L-1 sodium chloride (NaCl)). The findings revealed that NaCl stress increased antioxidant enzymes activities and decreased the content of nonenzymatic antioxidants such as ascorbate (AsA) and glutathione (GSH). Furthermore, the content of osmoregulatory substances like soluble proteins and proline was raised. Moreover, salt stress increased reactive oxygen species (ROS) content in the leaves of the two varieties. However, spraying with Hemin increased the activities of antioxidants such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) and accelerated AsA-GSH cycling to remove excess ROS. In summary, Hemin reduced the effect of salt stress on the physiological characteristics of rice leaves due to improved antioxidant defense mechanisms that impeded lipid peroxidation. Thus, Hemin was demonstrated to lessen the damage caused by salt stress.

Effects of moxibustion with wheat-grain size cone at "Zusanli" (ST 36) on vascular injury and oxidative stress in high-fat diet rats through mTOR/HIF-1α/VEGF signaling pathway. / 基于mTOR/HIF-1α/VEGF信号通路探讨麦粒灸"足三里"å¯¹é«˜è„‚é¥®é£Ÿå¤§é¼ è¡€ç®¡æŸä¼¤å’Œæ°§åŒ–åº”æ¿€çš„å½±å“.

OBJECTIVES: To explore the effect mechanism of moxibustion with wheat-grain size cone at "Zusanli" (ST 36) on vascular injury and oxidative stress in hyperlipidemia through mammalian target of rapamycin (mTOR)/hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway. METHODS: Forty healthy male SD rats with SPF grade were randomly divided into a normal group, a model group, a moxibustion group, and an inhibitor group, with 10 rats in each one. The hyperlipidemia model was established by feeding a high-fat diet for 8 weeks in rats of the model group, the moxibustion group and the inhibitor group. The moxibustion with wheat-grain size cone was delivered at bilateral "Zusanli" (ST 36) of each rat in the moxibustion group and the inhibitor group, with 3 cones on each acupoint in each intervention, once daily for 4 weeks. In the inhibitor group, before each intervention with moxibustion, rapamycin solution was injected intraperitoneally, 2.0 mg/kg. After modeling and intervention, using ELISA, the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the serum of rats were determined. After intervention, with HE staining and oil red O staining adopted, the abdominal aortic morphology and peripheral lipid deposition were observed. Separately, using WST-1, TBA and micro-plate method, the superoxide dismutase (SOD) activity and the levels of malondialdehyde (MDA) and nitric oxide (NO) in the serum were detected. The protein expression of mTOR, HIF-1α and VEGF in abdominal aorta were measured by Western blot method. RESULTS: Compared with those in the normal group, the levels of TC, TG and LDL-C increased (P<0.01) and HDL-C decreased (P<0.01) in the serum of the rats in the model group, the moxibustion group and the inhibitor group after model establishment. When compared with the normal group after intervention, in the model group, the serum levels of TC, TG, LDL-C and MDA increased (P<0.01), HDL-C level, SOD activity and NO level were reduced (P<0.01); the cell structure of the abdominal arota was abnormal, the peripheral lipids deposited seriously; and the protein expression of mTOR, HIF-1α and VEGF of abdominal aorta was elevated (P<0.01, P<0.05). In comparison with the model group, the levels of TC, TG, LDL-C and MDA were reduced (P<0.01), HDL-C levels, SOD activities and NO levels elevated (P<0.01, P<0.05), as well as the protein expression of mTOR, HIF-1α and VEGF of abdominal aorta (P<0.01, P<0.05) in the moxibustion group and the inhibitor group; besides, the vascular structure was ameliorated and the lipid deposition reduced in the moxibustion group, while, the vascular structure was still abnormal and the lipid deposition declined in the inhibitor group. When compared with the inhibitor group, the serum SOD activity and NO level increased (P<0.05) and MDA decreased (P<0.05); and the protein expression of mTOR, HIF-1α and VEGF of abdominal aorta was elevated (P<0.01, P<0.05) in the moxibustion group. CONCLUSIONS: The vascular injury due to hyperlipidemia is repaired by moxibustion with wheat-grain size cone at "Zusanli" (ST 36) through ameliorating oxidative stress, which is associated potentially with the modulation of mTOR/HIF-1α/VEGF signaling pathway.

[Ginsenoside Re regulates mitochondrial biogenesis through Nrf2/HO-1/PGC-1α pathway to reduce hypoxia/reoxygenation injury in H9c2 cells].

This article explored the mechanism by which ginsenoside Re reduces hypoxia/reoxygenation(H/R) injury in H9c2 cells by regulating mitochondrial biogenesis through nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/peroxisome prolife-rator-activated receptor gamma coactivator-1α(PGC-1α) pathway. In this study, H9c2 cells were cultured in hypoxia for 4 hours and then reoxygenated for 2 hours to construct a cardiomyocyte H/R injury model. After ginsenoside Re pre-administration intervention, cell activity, superoxide dismutase(SOD) activity, malondialdehyde(MDA) content, intracellular reactive oxygen species(Cyto-ROS), and intramitochondrial reactive oxygen species(Mito-ROS) levels were detected to evaluate the protective effect of ginsenoside Re on H/R injury of H9c2 cells by resisting oxidative stress. Secondly, fluorescent probes were used to detect changes in mitochondrial membrane potential(ΔΨ_m) and mitochondrial membrane permeability open pore(mPTP), and immunofluorescence was used to detect the expression level of TOM20 to study the protective effect of ginsenoside Re on mitochondria. Western blot was further used to detect the protein expression levels of caspase-3, cleaved caspase-3, Cyto C, Nrf2, HO-1, and PGC-1α to explore the specific mechanism by which ginsenoside Re protected mitochondria against oxidative stress and reduced H/R injury. Compared with the model group, ginse-noside Re effectively reduced the H/R injury oxidative stress response of H9c2 cells, increased SOD activity, reduced MDA content, and decreased Cyto-ROS and Mito-ROS levels in cells. Ginsenoside Re showed a good protective effect on mitochondria by increasing ΔΨ_m, reducing mPTP, and increasing TOM20 expression. Further studies showed that ginsenoside Re promoted the expression of Nrf2, HO-1, and PGC-1α proteins, and reduced the activation of the apoptosis-related regulatory factor caspase-3 to cleaved caspase-3 and the expression of Cyto C protein. In summary, ginsenoside Re can significantly reduce I/R injury in H9c2 cells. The specific mechanism is related to the promotion of mitochondrial biogenesis through the Nrf2/HO-1/PGC-1α pathway, thereby increasing the number of mitochondria, improving mitochondrial function, enhancing the ability of cells to resist oxidative stress, and alleviating cell apoptosis.

[Tanshinone â ¡_A inhibits ferroptosis via Nrf2 signaling pathway to protect liver in rats of non-alcoholic fatty liver disease].

This study investigated the protective effect of tanshinone Ⅱ_A(TSⅡ_A) on the liver in the rat model of non-alcoholic fatty liver disease(NAFLD) and the mechanism of TSⅡ_A in regulating ferroptosis via the nuclear factor E2-related factor 2(Nrf2) signaling pathway. The rat model of NAFLD was established with a high-fat diet for 12 weeks. The successfully modeled rats were assigned into model group, low-and high-dose TSⅡ_A groups, and inhibitor group, and normal control group was set. Enzyme-linked immunosorbent assay was employed to determine the content of superoxide dismutase(SOD) and malondialdehyde(MDA) in the serum of rats in each group. A biochemical analyzer was used to measure the content of aspartate aminotransferase(AST), alaninl aminotransferase(ALT), total cholesterol(TC), and triglycerides(TG). Hematoxylin-eosin(HE) staining was used to detect pathological damage in liver tissue. Terminal-deoxynucleoitidyl transferase-mediated nick end labeling(TUNEL) was employed to examine the apoptosis of the liver tissue. Oil red O staining, MitoSOX staining, and Prussian blue staining were conducted to reveal lipid deposition, the content of reactive oxygen species(ROS), and iron deposition in liver tissue. Western blot was employed to determine the expression of Nrf2, heme oxygenase-1(HO-1), glutathione peroxidase 4(GPX4), ferroptosis suppressor protein 1(FSP1), B cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) in the liver tissue. The result showed that TSⅡ_A significantly reduced the content of MDA, AST, ALT, TC, and TG in the serum, increased the activity of SOD, decreased the apoptosis rate, lipid deposition, ROS, and iron deposition in the liver tissue, up-regulated the expression of Nrf2, HO-1, FSP1, GPX, and Bcl-2, and inhibited the expression of Bax in the liver tissue of NAFLD rats. However, ML385 partially reversed the protective effect of TSⅡ_A on the liver tissue. In conclusion, TSⅡ_A could inhibit ferroptosis in the hepatocytes and decrease the ROS and lipid accumulation in the liver tissue of NAFLD rats by activating the Nrf2 signaling pathway.

Protective effect and pharmacokinetics of dihydromyricetin nanoparticles on oxidative damage of myocardium.

PURPOSE: This study aims to investigate the protective mechanism of dihydromyricetin PLGA nanoparticles (DMY-PLGA NPs) against myocardial ischemia-reperfusion injury (MIRI) in vitro and the improvement of oral bioavailability in vivo. METHODS: DMY-PLGA NPs was prepared and characterized by emulsifying solvent volatilization, and the oxidative stress model of rat H9c2 cardiomyocyte induced by H2O2 was established. After administration, cell survival rate, lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) were detected, and the expressions of PGC1α and PPARα were detected by western blot (WB). At the same time, the pharmacokinetics in rats were studied to explore the improvement of bioavailability. RESULTS: DMY-PLGA NPs can significantly increase cell survival rate, decrease LDH and MDA content, increase SOD content and PGC1α、PPARα protein expression. Compared with DMY, the peak time of DMY-PLGA NPs was extended (P<0.1), and the bioavailability was increased by 2.04 times. CONCLUSION: DMY-PLGA NPs has a significant protective effect on H9c2 cardiomyocytes, which promotes the absorption of DMY and effectively improves bioavailability.

Elucidating the modulatory effect of melatonin on enzyme activity and oxidative stress in wheat: a global meta-analysis.

In our comprehensive meta-analysis, we initially collected 177 publications focusing on the impact of melatonin on wheat. After meticulous screening, 40 published studies were selected, encompassing 558 observations for antioxidant enzymes, 312 for reactive oxygen species (ROS), and 92 for soluble biomolecules (soluble sugar and protein). This analysis revealed significant heterogeneity across studies (I2 > 99% for enzymes, ROS, and soluble biomolecules) and notable publication bias, indicating the complexity and variability in the research field. Melatonin application generally increased antioxidant enzyme activities [superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX)] in wheat, particularly under stress conditions, such as high temperature and heavy-metal exposure. Compared to control, melatonin application increased SOD, POD, CAT, and APX activities by 29.5, 16.96, 35.98, and 171.64%, respectively. Moreover, oxidative stress markers like hydrogen peroxide (H2O2), superoxide anion (O2), and malondialdehyde (MDA) decreased with melatonin by 23.73, 13.64, and 21.91%, respectively, suggesting a reduction in oxidative stress. The analysis also highlighted melatonin's role in improving carbohydrate metabolism and antioxidant defenses. Melatonin showed an overall increase of 12.77% in soluble sugar content, and 22.76% in glutathione peroxidase (GPX) activity compared to the control. However, the effects varied across different wheat varieties, environmental conditions, and application methods. Our study also uncovered complex relationships between antioxidant enzyme activities and H2O2 levels, indicating a nuanced regulatory role of melatonin in oxidative stress responses. Our meta-analysis demonstrates the significant role of melatonin in increasing wheat resilience to abiotic stressors, potentially through its regulatory impact on antioxidant defense systems and stress response.

Neuroprotective Assessment of Betaine against Copper Oxide Nanoparticle-Induced Neurotoxicity in the Brains of Albino Rats: A Histopathological, Neurochemical, and Molecular Investigation.

Copper oxide nanoparticles (CuO-NPs) are commonly used metal oxides. Betaine possesses antioxidant and neuroprotective activities. The current study aimed to investigate the neurotoxic effect of CuO-NPs on rats and the capability of betaine to mitigate neurotoxicity. Forty rats; 4 groups: group I a control, group II intraperitoneally CuO-NPs (0.5 mg/kg/day), group III orally betaine (250 mg/kg/day) and CuO-NPs, group IV orally betaine for 28 days. Rats were subjected to neurobehavioral assessments. Brain samples were processed for biochemical, molecular, histopathological, and immunohistochemical analyses. Behavioral performance of betaine demonstrated increasing locomotion and cognitive abilities. Group II exhibited significantly elevated malondialdehyde (MDA), overexpression of interleukin-1 beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α). Significant decrease in glutathione (GSH), and downregulation of acetylcholine esterase (AChE), nuclear factor erythroid 2-like protein 2 (Nrf-2), and superoxide dismutase (SOD). Histopathological alterations; neuronal degeneration, pericellular spaces, and neuropillar vacuolation. Immunohistochemically, an intense immunoreactivity is observed against IL-1ß and glial fibrillary acidic protein (GFAP). Betaine partially neuroprotected against CuO-NPs associated alterations. A significant decrease at MDA, downregulation of IL-1ß, and TNF-α, a significant increase at GSH, and upregulation of AChE, Nrf-2, and SOD. Histopathological alterations partially ameliorated. Immunohistochemical intensity of IL-1ß and GFAP reduced. It is concluded that betaine neuroprotected against most of CuO-NP neurotoxic effects through antioxidant and cell redox system stimulating efficacy.

Dexmedetomidine protects the uterus against ischemia-reperfusion injury in rats.

OBJECTIVE: This study aimed to analyze the histopathological and biochemical effects of dexmedetomidine on the rat uteri exposed to experimental ischemia-reperfusion injury. MATERIALS AND METHODS: Twenty-four female rats were randomly divided into three groups. Group 1 was defined as the control group. An experimental uterine ischemia-reperfusion model was created in Group 2. Group 3 was assigned as the treatment group. Similar uterine ischemia-reperfusion models were created for the rats in Group 3, and then, unlike the other groups, 100 µg/kg of dexmedetomidine was administered intraperitoneally immediately after the onset of reperfusion. In blood biochemical analysis, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA), interleukin 1beta (IL-1ß), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were measured. In the histopathological analyses, endometrial epithelial glandular changes (leukocytosis, cell degeneration) and endometrial stromal changes (congestion, edema) were analyzed using the tissue damage scoring system. RESULTS: It was observed that IL-1ß, IL-6, and TNF-α levels were significantly suppressed in Group 3 compared to Group 2 (p=0.001, p<0.001 and p=0.001, respectively). MDA level was noted as the highest in Group 2. The MDA value in Group 3 was measured at 5.37±0.82, which was significantly decreased compared to Group 2 (p<0.001). An increase in antioxidant enzyme activities (SOD and GSH-PX) was observed in Group 3 compared to Group 2 (p=0.001 and p=0.006, respectively). In our histopathological analysis, a significant improvement in endometrial epithelial glandular and endometrial stromal changes was revealed in Group 3 compared to Group 2 (p<0.001). CONCLUSIONS: In our study, it has been documented that dexmedetomidine protects the uterine tissue against ischemia-reperfusion injury.

Effects of adenosine triphosphate, Lacidipine, and Benidipine on 5-fluorouracil-induced kidney damage in rats.

OBJECTIVE: In the present study, the protective effects of adenosine triphosphate (ATP), Benidipine, and Lacidipine on potential kidney damage induced by 5-fluorouracil (5-FU) were investigated in rats. MATERIALS AND METHODS: Totally 48 rats were divided into 8 groups: healthy (HG), 5-FU (FUG), ATP+5-FU (AFU), Benidipine+5-FU (BFU), Lacidipine+5-FU (LFU), ATP+Benidipine+5-FU (ABFU), ATP+Lacidipine+5-FU (ALFU) and Benidipine+Lacidipine+5-FU (BLFU). In a 10-day period, ATP (4 mg/kg) was administered intraperitoneally, and Benidipine (4 mg/kg) and Lacidipine (4 mg/kg) were administered orally once a day. On days 1, 3, and 5, 5-FU (100 mg/kg) was administered intraperitoneally one hour after the drug was administered. Afterward, the rats were euthanized, and kidney tissues were removed. An analysis of malondialdehyde, total glutathione, superoxide dismutase, and catalase was performed on tissues, as well as a histopathological examination. A creatinine and blood urea nitrogen analysis were performed on blood samples. RESULTS: It was revealed that 5-FU decreased the amount of total glutathione, superoxide dismutase, and catalase activities in rat kidney tissues and increased malondialdehyde. Further, increased serum creatinine and blood urea nitrogen levels, as well as histopathological examination of kidney tissues, were found in the 5-FU group. ATP+Benidipine and ATP treatments were the most effective in preventing both biochemical and histopathological changes induced by 5-FU. A treatment with Benidipine improved biochemical and histopathologic data, but not to the same extent as a treatment with ATP+Benidipine and ATP. As a result of Lacidipine+ATP combination, 5-FU-induced biochemical changes in kidney tissue were partially inhibited, but the degree of histopathologic damage remained unchanged. Neither Benidipine+Lacidipine nor Lacidipine showed a protective effect on both biochemical changes and histopathologic damage. CONCLUSIONS: It may be possible to prevent nephrotoxicity by adding ATP + Benidipine or ATP to 5-FU treatment.

Effect of resistance training plus enriched probiotic supplement on sestrin2, oxidative stress, and mitophagy markers in elderly male Wistar rats.

This study aimed to determine the effects of resistance training combined with a probiotic supplement enriched with vitamin D and leucine on sestrin2, oxidative stress, antioxidant defense, and mitophagy markers in aged Wistar rats. Thirty-five male rats were randomly assigned to two age groups (old with 18-24 months of age and young with 8-12 weeks of age) and then divided into five groups, including (1) old control (OC: n = 5 + 2 for reserve in all groups), (2) young control (YC: n = 5), (3) old resistance training (OR: n = 5), (4) old resistance training plus supplement (ORS: n = 5), and old supplement group (OS: n = 5). Training groups performed ladder climbing resistance training 3 times per week for 8 weeks. Training intensity was inserted progressively, with values equal to 65, 75, and 85, determining rats' maximal carrying load capacity. Each animal made 5 to 8 climbs in each training session, and the time of each climb was between 12 and 15 s, although the time was not the subject of the evaluation, and the climbing pattern was different in the animals. Old resistance plus supplement and old supplement groups received 1 ml of supplement 5 times per week by oral gavage in addition to standard feeding, 1 to 2 h post training sessions. Forty-eight hours after the end of the training program, 3 ml of blood samples were taken, and all rats were then sacrificed to achieve muscle samples. After 8 weeks of training, total antioxidant capacity and superoxide dismutase activity levels increased in both interventions. A synergistic effect of supplement with resistance training was observed for total antioxidant capacity, superoxide dismutase, and PTEN-induced kinase 1. Sestrin 2 decreased in intervention groups. These results suggest that resistance training plus supplement can boost antioxidant defense and mitophagy while potentially decreasing muscle strength loss.

Superoxide dismutases: marker in predicting reduced left ventricular ejection fraction in patients with type 2 diabetes and acute coronary syndrome.

AIM: To examine the prognostic value of superoxide dismutase (SOD) activity for monitoring reduced left ventricular ejection fraction(LVEF)in the patients with type 2 diabetes and acute coronary syndrome (ACS). METHODS: The population of this cross-sectional study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2016 to January 2021. RESULTS: Diabetic patients with ACS were divided into 2 subgroups based on LVEF. The mean SOD activity was significantly lower in patients with an LVEF ≤ 45% than in those with an LVEF > 45% (149.1 (146.4, 151.9) versus 161.9 (160.8, 163.0)). Using ROC statistic, a cut-off value of 148.8 U/ml indicated an LVEF ≤ 45% with a sensitivity of 51.6% and a specificity of 73.7%. SODs activity were found to be correlated with the levels of NT-proBNP, hs-cTnT, the inflammatory marker CRP and fibrinogen. Despite taking the lowest quartile as a reference (OR 0.368, 95% CI 0.493-0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482-0.880, P = 0.005), SOD activity was found to be a stronger predictor of reduced LVEF than CRP and fibrinogen, independent of confounding factors. CONCLUSIONS: Our cross-sectional study suggests that SOD activity might be a valuable and easily accessible tool for assessing and monitoring reduced LVEF in the diabetic patients with ACS.

Physiological and oxidative stress response of carrot (Daucus carota L.) to jumping plant-louse Bactericera trigonica Hodkinson (Hemiptera: Psylloidea) infestation.

BACKGROUND: Carrot is an important vegetable crop grown worldwide. The major economic problem in carrot cultivation is yellow disease caused by Bactericera trigonica, which induces biotic stress and has the greatest impact on crop productivity. Comprehensive studies on the mechanism of carrot defense response to biotic stress caused by B. trigonica infestation have yet to be conducted. METHODS: The changes in photosynthetic pigments, proline, TPC, H2O2 and MDA content, DPPH radical scavenging ability, and antioxidant enzyme activity of SOD, CAT, and POX in carrot leaves in response to insect sex (female and male), rapid response (during the first six hours), and long-term response to B. trigonica infestation were evaluated. RESULTS: The results of our study strongly suggest that B. trigonica infestation causes significant changes in primary and secondary metabolism and oxidative status of carrot leaves. Photosynthetic pigment content, TPC, and DPPH and CAT activities were significantly reduced in carrot leaves in response to insect infestation. On the other hand, proline, H2O2 content, and the activity of the antioxidant enzymes superoxide dismutase and peroxidase were increased in carrot leaves after B. trigonica infestation. The results indicate that B. trigonica attenuates and delays the oxidative stress responses of carrot, allowing long-term feeding without visible changes in the plant. Carrot responded to long-term B. trigonica infestation with an increase in SOD and POX activity, suggesting that these enzymes may play a key role in plant defense mechanisms. CONCLUSIONS: This is the first comprehensive study strongly suggesting that B. trigonica infestation causes significant changes in primary and secondary metabolism and an attenuated ROS defense response in carrot leaves that enables long-term insect feeding. The information provides new insights into the mechanisms of carrot protection against B. trigonica infestation.

In vitro assessment of the anthelmintic activity of copper oxide and zinc oxide nanoparticles on egg and adult stages of Fasciola hepatica: evidence on oxidative stress biomarkers, and DNA damage.

OBJECTIVES: Fasciolosis is of significant economic and public health importance worldwide. The lack of a successful vaccine and emerging resistance in flukes to the drug of choice, triclabendazole, has initiated the search for alternative approaches. In recent years, metallic nanoparticles have been extensively investigated for their anthelmintic effects. This study investigates the in vitro anthelmintic activity of copper oxide and zinc oxide nanoparticles against Fasciola hepatica. METHODS: The in vitro study was based on egg hatchability test (EHA), adult motility inhibition tests, DNA damage, ROS levels, as well as several biomarkers of oxidative stress, including glutathione peroxidase (GSH) and glutathione S-transferase (GST), superoxide dismutase (SOD) and malondialdehyde (MDA). For this purpose, different concentrations of copper oxide nanoparticles (CuO-NPs) and Zinc oxide nanoparticles (ZnO-NPs) (1, 4, 8, 12, and 16 ppm) were used to evaluate the anthelmintic effect on different life stages, including egg and adults of Fasciola hepatica, over 24 h. RESULTS: In vitro treatment of F. hepatica worms with both CuO-NPs and ZnO-NPs could significantly increase ROS production and oxidative stress induction (decreased SOD, GST and GSH and increased MDA) compared to control group. CONCLUSIONS: Based on the results, it seems that CuO-NPs and ZnO-NPs may be effective in the control and treatment of F. hepatica infection. Further research is needed to investigate their potential for in vivo use in the treatment of parasitic infections.

[Correlation between CRAB Symptoms and Antioxidant Enzyme Activity in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the relationship between clinical indicators of CRAB symptoms and antioxidant enzyme activity in patients with multiple myeloma (MM). METHODS: The activity of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in the bone marrow supernatants of 44 patients with MM and 12 patients with non-malignant hematological diseases was detected by colorimetric assay, and then the differences in the activity of antioxidant enzymes between the two groups were compared. Furthermore, the relationship between the activity of antioxidant enzymes in the MM group and the levels of serum calcium, serum creatinine (Scr), hemoglobin (Hb), alkaline phosphatase (ALP) as well as bone lesions were analyzed. RESULTS: The antioxidant enzyme activity was lower in MM patients compared with the control group (P < 0.05). When the concentrations of serum calcium and ALP were higher than the normal levels, Hb was lower than 85 g/L, and there were multiple bone lesions, the activity of CAT, SOD and GPX was significantly declined (P < 0.05); When the concentration of Scr≥177 µmol/L, the activity of GPX was significantly declined (P < 0.05). Regression analyses showed that CAT, SOD and GPX were negatively correlated with serum calcium (r =-0.538, r =-0.456, r =-0.431), Scr (r =-0.342, r =-0.384, r =-0.463), and ALP (r =-0.551, r =-0.572, r =-0.482). CONCLUSION: The activity of antioxidant enzymes, including CAT, SOD and GPX, were decreased in patients with MM and they were negatively correlated with some clinical indicators of CRAB symptoms (such as serum calcium, Scr, and ALP), which suggests that promoting the activity of antioxidant enzymes may be beneficial to treat the CRAB symptoms of the patients with MM.

Impact of latent toxoplasmosis on pneumonic and non-pneumonic COVID-19 patients with estimation of relevant oxidative stress biomarkers.

Susceptibility to COVID-19, the most devastating global pandemic, appears to vary widely across different population groups. Exposure to toxoplasmosis has been proposed as a theory to explain the diversity of these populations. The aim of the present study was to investigate the possible association between latent toxoplasmosis and COVID-19 and its probable correlation with markers of oxidative stress, C-reactive protein (CRP) and ferritin. In a case-control study, blood samples were collected from 91 confirmed (48 non-pneumonic; NP, and 43 pneumonic; P) COVID-19 patients and 45 healthy controls. All participants were tested for IgG anti-Toxoplasma gondii antibodies and oxidative stress markers (nitric oxide [NO], superoxide dismutase [SOD] and reduced glutathione [GSH]), and CRP and serum ferritin levels were determined. In COVID-19 patients, IgG anti-T. gondii antibodies were found in 54% compared to 7% in the control group, with the difference being statistically significant (P ˂ 0.001). However, no significant correlation was found between the severity of COVID-19 and latent T. gondii infection. Latent toxoplasmosis had a strong influence on the risk of COVID-19. NO and SOD levels were significantly increased in COVID-19 patients, while GSH levels decreased significantly in them compared to control subjects (P ˂ 0.001 for both values). CRP and ferritin levels were also significantly elevated in P COVID-19 patients infected with toxoplasmosis. This is the first study to look at the importance of oxidative stress indicators in co-infection between COVID-19 and T. gondii. The high prevalence of latent toxoplasmosis in COVID-19 suggests that T. gondii infection can be considered a strong indicator of the high risk of COVID-19.

Vincamine alleviates brain injury by attenuating neuroinflammation and oxidative damage in a mouse model of Parkinson's disease through the NF-κB and Nrf2/HO-1 signaling pathways.

Parkinson's disease (PD) is a neurodegenerative disease featured by progressive loss of nigrostriatal dopaminergic neurons, the etiology of which is associated with the existence of neuroinflammatory response and oxidative stress. Vincamine is an indole alkaloid that was reported to exhibit potent anti-inflammatory and antioxidant properties in many central and/or peripheral diseases. Nevertheless, the specific role of vincamine in PD development remains unknown. In our study, dopaminergic neuron loss was determined through immunohistochemistry staining and western blot analysis of tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of PD mice. Reactive oxygen species (ROS) production and malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were detected through DHE staining and commercially available kits to assess oxidative stress. Pro-inflammatory cytokine (TNF-α, IL-1ß, and IL-6) levels in the SN were measured via RT-qPCR and western blot analysis. Microglial and astrocyte activation was examined through immunofluorescence staining of Iba-1 (microglia marker) and GFAP (astrocyte marker) in the SN. The regulation of vincamine on the NF-κB and Nrf2/HO-1 pathway was estimated through western blot analysis. Our results showed that vincamine treatment decreased TNF-α, IL-1ß, and IL-6 mRNA and protein levels, reduced GFAP and Iba-1 expression, decreased ROS production and MDA level, and increased SOD activity and GSH level in the SN of PD mice. Mechanically, vincamine repressed the phosphorylation levels of p65, IKKß, and IκBα but enhanced the protein levels of Nrf2 and HO-1 in PD mice. Collectively, vincamine plays a neuroprotective role in PD mouse models by alleviating neuroinflammation and oxidative damage via suppressing the NF-κB pathway and activating the Nrf2/HO-1 pathway.