GPx Activity Research Articles

Role of parthenolide in paclitaxel-induced oxidative stress injury and impaired reproductive function in rat testicular tissue

The chemotherapeutic agent paclitaxel (PTX) causes testicular toxicity due to oxidative stress. Parthenolide (PTL), the active ingredient of the Tanacetum parthenium plant, is used to treat inflammation, dizziness, and spasms. In the present study, we evaluated the therapeutic effect of PTL on PTX-induced testicular toxicity in rats and its role in reproductive function. To this end, 6 groups were formed: control, PTX, sham, T1, T2, and T3. After testicular toxicity was induced in rats with 8 mg/kg PTX, the rats were treated with 1 mg/kg, 2 mg/kg, and 4 mg/kg PTL for 14 days. GSH and MDA levels were measured in rat testicular tissue after the last dose of PTL was administered. To determine the damage caused by PTX to testicular tissue by detecting 8-OHdG and iNOS, sections were prepared and examined histopathologically and immunohistochemically. Furthermore, the gene expressions and enzymatic activities of SOD, CAT, GPx, GST, and GR were investigated in all groups. After PTL treatment, MDA, 8-OHdG, and iNOS levels decreased while GSH levels increased in testicular tissue. Increased levels of antioxidant genes and enzymes also reduced oxidative stress. Additionally, the expression levels of the Dazl, Ddx4, and Amh genes, which are involved in gametogenesis and sperm production, decreased in case of toxicity and increased with PTL treatment. The data from this study show that PTL may have a therapeutic effect in the treatment of testicular damage by eliminating the oxidative stress-induced damage caused by PTX in testicular tissue, providing an effective approach to alleviating testicular toxicity, and playing an important role in reproduction/sperm production, especially at a dose of 4 mg/kg.

Melatonin acts through different mechanisms to control oxidative stress and primordial follicle activation and survival during in vitro culture of bovine ovarian tissue

This study aims to evaluate the effects of melatonin and its mechanisms of action on preantral follicle activation and survival, stromal cell density and collagen distribution in extracellular matrix (ECM). The involvement of melatonin receptors and mTORC1 pathway in these procedures were also investigated. To this end, ovarian fragments were cultured for six days in α‐MEM+ alone or supplemented with 1000 pM melatonin, 1000 pM melatonin with 1000 pM luzindole (inhibitor of melatonin receptors), or 1000 pM melatonin with 0.16 µg/ml rapamycin (mTORC1 inhibitor). At the end of culture period, tissues were processed for classical histology, and the follicles were classified as normal or degenerated, as well as in primordial or growing follicles. The ovarian stromal cell density and ECM collagen distribution were also evaluated. Samples of ovarian tissues were also destined to measure the levels of thiol and mRNA for CAT, SOD, GPX1 and PRDX1, as well as the activity of antioxidant enzymes CAT, SOD, and GPX1. The results demonstrated that ovarian tissues cultured with melatonin, melatonin with luzindole or melatonin with rapamycin had significantly higher percentage of morphologically normal follicles than those cultured in control medium (α‐MEM+). However, the presence of either luzindole or rapamycin, did not block the positive effects of melatonin on follicle survival (P > 0.05). Although the presence of melatonin in culture medium reduced the percentage of primordial follicles and increased the percentage of development follicles, these positive effects of melatonin were blocked by either luzindole or rapamycin (P < 0.05). Melatonin, melatonin with luzindole or melatonin with rapamycin did not influence the number of ovarian stromal cells. In contrast, melatonin significantly increased the percentages of collagen in ovarian tissues, but the positive effects of melatonin were blocked by either luzindole or rapamycin. Tissues cultured with melatonin and rapamycin had higher levels of mRNA for CAT and lower GPx activity when compared to those cultured in control medium. In conclusion, melatonin promotes primordial follicle activation, increases collagen fiber in ECM of in vitro cultured bovine ovarian tissue through its membrane-coupled receptors and mTORC1. Oppositely, melatonin increase follicles survival by acting through other pathways, since it can pass through cell membranes and directly regulate oxidative stress.

Gamma-aminobutyric acid modulates antioxidant and osmoprotective systems in seedlings of Triticum aestivum cultivars differing in drought tolerance

The stress-protective effects of plant neurotransmitters, including gamma-aminobutyric acid (GABA) have been intensively examined in recent years. However, studies on the GABA influence on stress protective systems in bread wheat cultivars with different drought adaptation strategies are still lacking. The aim of this work was to estimate the GABA effect on the state of antioxidant and osmoprotective systems in etiolated seedlings of two wheat cultivars differing significantly in drought tolerance, namely Doskonala (non-drought-resistant) and Tobak (drought-resistant) under model drought induced by PEG 6000. Two-day-old seedlings were transferred to 15% PEG 6000 and incubated for two days in the absence or presence of GABA. Treatment with 0.1 and 0.5 mM GABA significantly reduced the growth-inhibitory effect of PEG 6000 on the roots and shoots of both cultivars, but to a greater extent on those of non-resistant Doskonala. It was shown that GABA treatment reduced drought-induced accumulation of H2O2 and MDA, stabilized SOD and GPX activity, the level of sugars, anthocyanins and flavonoids in seedlings of both cultivars. Meanwhile GABA treatment enhanced the stress-induced increase in proline content in the Doskonala cultivar, but decreased it in the Tobak, completely prevented stress induced decrease in anthocyanins and flavonoids level in the Tobak and only partially in Doskonala cultivar. Thus, the stabilization of the stress-protective systems functioning in the wheat cultivars and variety-dependent differences in response to GABA were revealed. Keywords: anthocyanins, antioxidant system, drought resistance, gamma-aminobutyric acid, oxidative stress, proline, Triticum aestivum

Comparative transcriptome analysis of gene responses of salt-tolerant and salt-sensitive rice cultivars to salt stress

Salt stress is one unfavorable factor of global climate change that adversely affects rice plant growth and yield. To identify novel salt-tolerant genes and new varieties of salt-tolerant rice, a better understanding of the molecular regulation mechanism of salt tolerance in rice is needed. In this study we used transcriptome analyses to examine changes in gene expression of salt-tolerant and salt-sensitive rice plants. The salt-tolerant cultivar HH11 and salt-sensitive cultivar IR29 were treated with 200 mM NaCl solution for 0 h, 6 h, 24 h and 48 h at the three leaf stage. Physiological parameters and transcriptome were measured and analyzed after each treatment. Activity of SOD and POD, as well as the MDA and protein content of the two rice cultivars generally increased with increasing time of exposure to NaCl. Meanwhile, the APX activity first increased, then decreased in both cultivars, with maximum values seen at 6 h for IR29 and at 24 h for HH11. The GR and GPX activity of HH11 were stronger than that of IR29 in response to salt stress. The H2O2 content first increased at 0–6 h, then decreased at 6–24 h, and then increased again at 24–48 h under salt stress. Compared with IR29, SOD, POD and APX activity of HH11 was more sluggish in response to salt stress, reaching the maximum at 24 h or 48 h. The MDA, H2O2 and proline content of HH11 was lower than that of IR29 under salt stress. Relative to untreated HH11 plants (0 h) and those exposed to salt for 6 h, 24 h, and 48 h (H0-H6, H0-H24 and H0-H48), 7462, 6363 and 6636, differentially expressed genes (DEGs), respectively, were identified. For IR29, the respective total DEGs were 7566, 6075 and 6136. GO and KEGG enrichment analysis showed that metabolic pathways related to antioxidative responses and osmotic balance played vital roles in salt stress tolerance. Sucrose and starch metabolism, in addition to flavonoid biosynthesis and glutathione metabolism, showed positive responses to salt stress. Expression of two SPS genes (LOC_Os01g69030 and LOC_Os08g20660) and two GST genes (LOC_Os06g12290 and LOC_Os10g38740) was up-regulated in both HH11 and IR29, whereas expression of LOC_Os09g12660, a glucose-1-phosphate adenylyltransferase gene, and two SS genes (LOC_Os04g17650 and LOC_Os04g24430) was up-regulated differential expression in HH11. The results showed that HH11 had more favorable adjustment in antioxidant and osmotic activity than IR29 upon exposure to salt stress, and highlighted candidate genes that could play roles in the function and regulation mechanism of salt tolerance in rice.

Trace Elements Status and Their Associations With Related Antioxidant Enzyme Activities in Patients Receiving Peritoneal Dialysis and Hemodialysis

It remains ambiguous as to whether the status of trace elements would affect their related enzyme activities toward defending a possible higher oxidative stress in patients receiving peritoneal dialysis (PD) or hemodialysis (HD) treatment. We investigated copper (Cu), zinc (Zn), and selenium (Se) status in patients receiving PD or HD treatments and further determined the association of these trace elements with their related antioxidant capacities in those patients. Sixty PD and 80 HD patients before and after HD treatment had their blood drawn. Demographic, clinical, and 24-hour diet recall data were recorded and collected. Plasma trace elements, oxidative stress indicators, and antioxidant enzyme activities were measured. Patients receiving PD or HD treatments experienced similar Zn and Cu intakes. PD and HD patients displayed adequate mean plasma Cu, Zn, and Se levels. Patients receiving PD treatment showed significantly higher levels of Cu, Zn, advanced oxidation protein products (AOPPs), and superoxide dismutase (SOD) activity, but had significantly lower levels of Se and total antioxidant capacity when compared to levels in the HD patients at the pre-HD session. The levels of 3 trace elements and AOPP increased significantly, while the levels of glutathione (GSH), oxidized glutathione (GSSG), GPx, and SOD activities decreased significantly after receiving HD treatment than did the levels in the pre-HD session. Plasma Cu, Se, and Zn levels had a different correlation with plasma AOPP level, GPx, and SOD activities during PD, pre- or post-HD sessions. Plasma Cu, Zn, and Se levels did not have any association with their associated enzyme activities in patients with PD, while plasma Cu and Zn levels may have influenced SOD activity in HD patients. An adequate Cu, Zn, and Se status is required in order to help their associated enzyme activity cope with increased oxidative stress during PD or HD sessions.

Quantification of enzymatic antioxidants (catalase and peroxidase) and non-enzymatic antioxidants (ascorbic acid and chlorogenic acid) in the tender shoots of seven bamboo species and their products, found in Arunachal Pradesh, India

This study was undertaken to understand the anti-oxidative properties of products of both enzymatic and non-enzymatic origin derived from bamboo shoots of seven species, namely Dendrocalamus hamiltonii, Phyllostachys bambusoides, Bambusa tulda, Dendrocalamus giganteus, Bambusa pallida, Bambusa balcooa, and Gigantochola macrostachya, as well as three processed bamboo shoot products, namely Hidung (roasted and partially fermented shoot) Eup (moist fermented shoot), and Ekung (dried fermented shoot). The latter three products are widely consumed by the tribal people of Arunachal Pradesh, India. Catalase enzyme activities (CAT) among the shoots were significantly different (F = 18.574, P < 0.001) with the highest values being in B. balcooa and P. bambusoides (2.7 units/g sample) and the lowest in G. macrostachya (0.9 units/g sample), respectively. Peroxidase GPX activity among the shoots and processed products was also significantly different (F= 17.996, P < 0.001 and F= 8.75, P < 0.05, respectively) with a range of between 125.6 and 239.6 GPX units/g for fresh and 170.7–180.3 GPX units/g for processed products. Ascorbic acid contents in the tender shoots of all the species and processed products ranged from 2.35 to 6.1 mg/100 g for fresh tender shoots and 2.23–5.61 mg/100 g for processed products. Chlorogenic acid (CGA) content was estimated to be 0.22–1.16 mg/100 g for fresh material and 0.24–0.26 mg/100 g for processed products. Fresh tender shoots had higher antioxidative properties of both enzymatic and non-enzymatic origin than fermented and processed forms. Higher antioxidant levels were observed in partially fermented Hidung than in the other two processed forms. Bamboo shoots and their processed forms have an adequate level of antioxidant characteristics, making them a nutritious meal that may be included in a healthy diet plan.

The neuroprotective potential of turmeric rhizome and bitter melon on aspartame-induced spatial memory impairment in rats

Aspartame is widely used artificial sweetener. However, chronic exposure to aspartame led to spatial memory impairment and elevated oxidative stress in the brain. Extract of turmeric rhizome (Curcuma longa) (TUR) and extract of bitter melon (Momordica charantia) (BM) is known to have antioxidant activity. The present study was aimed to examine the neuroprotective potential of TUR and BM extracts, either as single or as combination, against the effects of aspartame in the brain. Here, Sprague-Dawley rats fed with aspartame (40 mg/kg BW) for 28 days were compared with rats fed with extract and aspartame. To assess neuroprotective potential, rats were given extract 7 days before and during aspartame treatment. Spatial memory was assessed with Morris water maze test followed with H&E staining of hippocampal region. Brain lipid peroxidation and enzymatic activity of malondialdehyde (MDA), glutathione peroxidase (GPx), and Acetylcholinesterase (AChE) were measured to probe status of oxidative stress in the brain. Aspartame-treated rats demonstrated spatial memory impairment and reduced number of hippocampal cells and elevated levels of MDA, downregulated activity of GPx and elevated activity of AChE. In contrast, animals received both aspartame and extract demonstrated better spatial memory function, higher number of hippocampal areas, increased GPX activity, reduced MDA levels, and decreased AChE activity were observed in the brain of extract-treated rats. Taken together, our results suggest that extract of TUR rhizome and BM fruit exhibit antioxidant activity which may contribute to the neuroprotective effects against aspartame-induced memory impairment in rats.

An integrated mycotoxin-mitigating agent can effectively mitigate the combined toxicity of AFB1, DON and OTA on the production performance, liver and oviduct health in broiler breeder hens

This study was to evaluate the efficacy of an integrated mycotoxin-mitigating agent in reducing the adverse effects of co-occurring dietary aflatoxin B1 deoxynivalenol and ochratoxin A on broiler breeder hens. 360 30-week-old Hubbard Efficiency Plus broiler breeder hens were allocated into four groups and received a basal diet (BD; Control), BD added 0.15 mg/kg aflatoxin B1+1.5 mg/kg deoxynivalenol+0.12 mg/kg ochratoxin A (Toxins), BD plus Toxins with 0.1% TOXO-XL (Toxins + XL1), and BD plus Toxins with 0.2% TOXO-XL (Toxins + XL2), respectively, for 8 weeks, and then received the same BD for another 4 weeks. Compared with control, mycotoxins decreased total egg weigh, egg laying rate, settable eggs rate, hatch of total eggs rate, egg quality, but increased feed/egg ratio and mortality rate, and impaired the liver and oviduct health during weeks 1–8 and(or) 9–12. It also increased PC and MDA concentrations, TUNEL-positive cells and IL-1β and IL-6 expression, and decreased T-AOC, GPX and CAT activities in liver and/or oviduct. Notably, most of these negative changes were mitigated by both dosages of TOXO-XL. Generally, 0.2% TOXO-XL displayed better mitigation effects than 0.1% TOXO-XL. Conclusively, these findings revealed that TOXO-XL could mitigate the combined mycotoxins-induced toxicity on the performance, liver and oviduct health, through the regulation of redox, immunity, and apoptosis in broiler breeder hens.

Toxic effects of triclocarban on the histological morphology, physiological and immune response in the gills of the black tiger shrimp Penaeus monodon

Triclocarban (TCC) is a widely used broad-spectrum antimicrobial agent that has become a pollutant threatening the health of aquatic animals. However, the toxic effects of TCC on Penaeus monodon are still lacking. In this study, we exposed P. monodon to 1 μg/L (TCC-1) and 10 μg/L TCC (TCC-10) for 14 days, and the changes of histological morphology, physiological and immune responses in the gills were investigated. The results showed that TCC exposure caused the deformation of the gill vessels and the disordered arrangement of the gill filaments. Oxidative stress biochemical indexes such as H2O2 content, CAT and GPx activity and the relative expression levels of antioxidant-related genes (SOD, GPx and Nrf2) were increased in the TCC-1 and TCC-10 groups; the levels of CAT and HSP70 genes were increased but POD activity was decreased in the TCC-10 group. The relative expression levels of endoplasmic reticulum (ER) stress indexes such as ERP15 and ATF-6 genes were increased in the TCC-10 group, while the level of GRP78 gene was decreased in the TCC-1 and TCC-10 groups. The relative expression levels of apoptosis indexes such as p53 and JNK genes were increased, but CytC and Casp-3 genes were decreased in the TCC-1 and TCC-10 groups. Furthermore, the relative expression levels of detoxification metabolism-related genes (cytP450 and GST) and osmotic regulation-related genes (NKA-α, NKA-β, CA, AQP, CLC and CCP) were increased in the TCC-10 group. The results showed that TCC exposure could affect the physiological homeostasis in the gills of P. monodon, probably via damaging histological morphology, inducing oxidative stress, and disordering ER stress, apoptosis, detoxification and osmotic regulation.

Sesamin: A Promising Therapeutic Agent for Ameliorating Symptoms of Diabetes

Diabetes is a chronic metabolic disease characterized by improperly regulating proteins, carbohydrates, and lipids due to insulin deficiency or resistance. The increasing prevalence of diabetes poses a tremendous socioeconomic burden worldwide, resulting in the rise of many studies on Chinese herbal medicines to discover the most effective cure for diabetes. Sesame seeds are among these Chinese herbal medicines that were found to contain various pharmacological activities, including antioxidant and anti-inflammatory properties, lowering cholesterol, improving liver function, blood pressure and sugar lowering, regulating lipid synthesis, and anticancer activities. These medicinal benefits are attributed to sesamin, which is the main lignan found in sesame seeds and oil. In this study, Wistar rat models were induced with type 2 diabetes using streptozotocin (STZ) and nicotinamide, and the effect of sesamin on the changes in body weight, blood sugar level, glycosylated hemoglobin (HbA1c), insulin levels, and the states of the pancreas and liver of the rats were evaluated. The results indicate a reduced blood glucose level, HbA1c, TG, and ALT and AST enzymes after sesamin treatment, while increased insulin level, SOD, CAT, and GPx activities were also observed. These findings prove sesamin’s efficacy in ameliorating the symptoms of diabetes through its potent pharmacological activities.

The Combined Effects of Toxic Microcystis aeruginosa and Thermal Stress on the Edible Clam (Corbicula fluminea): Insights into Oxidative Stress Responses and Molecular Networks.

Cyanobacterial blooms (CYBs) have become a global environmental issue, posing risks to edible bivalves. Toxic cyanobacteria and thermal stress represent the two key co-occurring stressors to bivalves experiencing CYBs. To investigate the combined effects of these stressors on the edible bivalve Corbicula fluminea, the responses to oxidative stress and the molecular mechanisms of physiological adaptations in C. fluminea were examined under co-exposure to toxic Microcystis aeruginosa and thermal stress. The activity of antioxidant enzymes, including GST, SOD, CAT, GPx and GR, was significantly influenced by the interaction between temperature and M. aeruginosa (p < 0.05). A positive correlation was observed between toxic M. aeruginosa exposure and elevated SOD and GPx activities at 30 °C, demonstrating that SOD and GPx may help C. fluminea defend effectively against MCs under thermal stress. Furthermore, significant interactive effects between toxic M. aeruginosa and temperature were also observed in ROS and MDA (p < 0.05). The results of the PCA and IBR index also evidenced the apparent influence of toxic M. aeruginosa and thermal stress on oxidative stress responses of C. fluminea. The eggNOG and GO annotations confirmed that a substantial portion of differentially expressed genes (DEGs) exhibited associations with responses to oxidative stress and transporter activity. Additionally, KEGG analysis revealed that abundant DEGs were involved in pathways related to inflammatory responses, immune functions and metabolic functions. These findings improve our understanding of the mechanism of the physiological adaptation in bivalves in response to cyanotoxins under thermal conditions, potentially enabling the evaluation of the viability of using bivalves as a bioremediation tool to manage CYBs in eutrophic waters.

Temporal dynamics of muscle mitochondrial uncoupling-induced integrated stress response and ferroptosis defense.

Mitochondria play multifaceted roles in cellular function, and impairments across domains of mitochondrial biology are known to promote cellular integrated stress response (ISR) pathways as well as systemic metabolic adaptations. However, the temporal dynamics of specific mitochondrial ISR related to physiological variations in tissue-specific energy demands remains unknown. Here, we conducted a comprehensive 24-hour muscle and plasma profiling of male and female mice with ectopic mitochondrial respiratory uncoupling in skeletal muscle (mUcp1-transgenic, TG). TG mice are characterized by increased muscle ISR, elevated oxidative stress defense, and increased secretion of FGF21 and GDF15 as ISR-induced myokines. We observed a temporal signature of both cell-autonomous and systemic ISR in the context of endocrine myokine signaling and cellular redox balance, but not of ferroptotic signature which was also increased in TG muscle. We show a progressive increase of muscle ISR on transcriptional level during the active phase (night time), with a subsequent peak in circulating FGF21 and GDF15 in the early resting phase. Moreover, we found highest levels of muscle oxidative defense (GPX and NQO1 activity) between the late active to early resting phase, which could aim to counteract excessive iron-dependent lipid peroxidation and ferroptosis in muscle of TG mice. These findings highlight the temporal dynamics of cell-autonomous and endocrine ISR signaling under skeletal muscle mitochondrial uncoupling, emphasizing the importance of considering such dissociation in translational strategies and sample collection for diagnostic biomarker analysis.

Heme Oxygenase-1 Is Involved in the Repair of Oxidative Damage Induced by Oxidized Fish Oil in Litopenaeus vannamei by Sulforaphane.

Heme oxygenase-1 (HO-1), which could be highly induced under the stimulation of oxidative stress, functions in reducing the damage caused by oxidative stress, and sulforaphane (SFN) is an antioxidant. This study aims to investigate whether HO-1 is involved in the repair of oxidative damage induced by oxidized fish oil (OFO) in Litopenaeus vannamei by sulforaphane (SFN). The oxidative stress model of L. vannamei was established by feeding OFO feed (OFO accounts for 6%), and they were divided into the following four groups: control group (injected with dsRNA-EGFP and fed with common feed), dsRNA-HO-1 group (dsRNA-HO-1, common feed), dsRNA-HO-1 + SFN group (dsRNA-HO-1, supplement 50 mg kg-1 SFN feed), and SFN group (dsRNA-EGFP, supplement 50 mg kg-1 SFN feed). The results showed that the expression level of HO-1 in the dsRNA-HO-1 + SFN group was significantly increased compared with the dsRNA-HO-1 group (p < 0.05). The activities of SOD in muscle and GPX in hepatopancreas and serum of the dsRNA-HO-1 group were significantly lower than those of the control group, and MDA content in the dsRNA-HO-1 group was the highest among the four groups. However, SFN treatment increased the activities of GPX and SOD in hepatopancreas, muscle, and serum and significantly reduced the content of MDA (p < 0.05). SFN activated HO-1, upregulated the expression of antioxidant-related genes (CAT, SOD, GST, GPX, Trx, HIF-1α, Nrf2, prx 2, Hsp 70), and autophagy genes (ATG 3, ATG 5), and stabilized the expression of apoptosis genes (caspase 2, caspase 3) in the hepatopancreas (p < 0.05). In addition, knocking down HO-1 aggravated the vacuolation of hepatopancreas and increased the apoptosis of hepatopancreas, while the supplement of SFN could repair the vacuolation of hepatopancreas and reduce the apoptosis signal. In summary, HO-1 is involved in the repair of the oxidative damage induced by OFO in L. vannamei by SFN.

The beneficial effect of nanomethionine supplementation on growth performance, gene expression profile, and histopathology of heat-stressed broiler chicken

This study investigated the effects of nanomethionine (nano-meth) on performance, antioxidants, and gene expression of HSP70, HSP90 and Heat Shock factor-1 (HSF-1) from the liver, and TLR4 from the jejunum, of broiler chickens reared under normal temperatures or under heat stress. Three hundred 1-day-old chicks were randomly assigned to 5 treatment groups. Group 1 served as control. Under normal temperature, birds in group 2 received nano-meth (10 mL/L of drinking water) from d1 until the experiment ended. Group 3 birds were heat-stressed (HS) and did not receive any supplementation. Group 4 received nano-meth in the same dose from d1 old until experiment ended, and the birds were exposed to HS. Group 5 birds were HS and received supplementation of nano-meth during the HS period only. Nano-meth improved (P < 0.0001) final body weight, weight gain, feed conversion ratio, and also decreased (P < 0.0001) the effect of HS on growth performance. Reduction (P < 0.0001) in malondialdehyde and changes in antioxidant enzymes GPX and CAT activity indicated the antioxidant effect of nano-meth. Nano-meth supplementation caused an increase in the expression of HSP70 , HSP90 and HSF1, and a downregulation of TLR4 gene expression. Additionally, nano-meth-supplemented groups showed marked improvement in the histological liver structure, intestinal morphology and villus height compared to control or HS groups.

Vanillic Acid Ameliorates Diethyl Phthalate and Bisphenol S -Induced Cardiotoxicity in rats via abrogating oxidative Stress

Abstract Background: Neglected home producing toxicants (NHPT) are the endocrine disruptors affecting biological systems. We investigated the effect of vanillic acid on diethyl phthalate (DEP) and bisphenol S (BPS)-induced cardio-toxicity and oxidative stress using rat model. Methods: Rats were exposed to DEP (50 mg/kg) and BPS (50 mg/kg) and treated with vanillic acid (25 and 50 mg/kg) by oral gavage for twenty-one days. Afterwards, they were sacrificed. Results: Vanillic acid treatment significantly (p &lt; 0.05) protected cardiac tissues architecture by abolishing the DEP+BPS-induced decrease in the activity of all the enzymatic antioxidants. Co-treatment with vanillic acid remarkably (p &lt; 0.05) reversed DEP+BPS-induced decreases in glutathione levels, GSH, CAT, GPx, and SOD activities in cardiac tissues, while attenuating DEP+BPS mediated increase in cardio-oxidative damage markers (MDA,AOPP, and NO as well as increase activity of arginase and PDE-5. Conclusion: Vanillic acid may have exert a cardio-protective effect against DEP+BPS induced cardiotoxicity by decreasing oxidative stress via its antioxidant, free radical scavenging effect.

Design and Mechanism Insight of Monodispersed AuCuPt Alloy Nanozyme with Antitumor Activity.

The abrogation of the self-adaptive redox evolution of tumors is promising for improving therapeutic outcomes. In this study, we designed a trimetallic alloy nanozyme AuCuPt-PpIX (ACPP), which mimics up to five naturally occurring enzymes: glucose oxidase (GOD), superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione peroxidase (GPx). Facilitated by these enzyme-mimicking traits, the constructed ACPP nanozymes can not only disrupt the established redox homeostasis in tumors through a series of enzymatic cascade reactions but also achieve cyclic regeneration of the relevant enzyme substrates. Density functional theory (DFT) calculations have theoretically explained the synergistic effect of multimetallic doping and the possible mechanism of enzymatic catalysis. The doped Cu and Pt sites are conducive to the adsorption, activation, and dissociation of reactant molecules, whereas the Au sites are conducive to desorption, which significantly improves catalytic efficiency via a synergistic effect. Additionally, ACPP nanozymes can improve the effect of protoporphyrin (PpIX)-enabled sonodynamic therapy (SDT) by alleviating hypoxia and initiating ferroptosis by inducing lipid peroxidation (LPO) and inhibiting GPX4 activity, thus achieving multimodal synergistic therapy. This study presents a typical paradigm to enable the use of multimetallic alloy nanozymes for the treatment of tumor cells with self-adaptive properties.

Evaluation of the Effect of Pollution on the Level of Antioxidant Enzymes in Freshwater Fishes

To assess the impact of polluted water on fishes, biochemical studies were carried out to determine the biochemical alterations in tissues of fishes collected from the control and upstream, midstream and downstream sites of the Varahanadhi river in Tamil Nadu, India. Two fish species such as Catla (Catla catla) and Mrigal (Cirrhinus mrigala) were taken and the tissues such as liver and kidney were excised and tissue homogenate was prepared. Using the tissue homogenate lipid peroxide and lipid hydroperoxide, CAT and SOD activity, GPx activity, GR and GST activities and non-enzymatic antioxidants such as vitamin C and vitamin E was estimated. An increase in lipid peroxide and lipid hydroperoxide level was observed in all the organs of fishes collected from the downstream site when compared with the control, upstream and midstream site of the river. A decrease in CAT and SOD activity and in non-enzymatic antioxidants such as vitamin C and vitamin E, increased Glutathione reductase and GST activities was observed in the fishes collected from the downstream site. These changes might be due to the exposure of fish to pollutants, industrial waste and heavy metals present in water sample causing adverse effects on fishes inhabiting the river.

Induction of ferroptosis cell death in acute promyelocytic leukemia cell lines (NB4 and HL-60) using hydrothermally synthesized ZnO NPs in the presence of black cardamom extract

This paper reports an effective, one-step, and eco-friendly method for producing ZnO nanoparticles (NPs) via the hydrothermal procedure. In the synthesis procedure, where 1,8-cineole is the dominant component, an optimized concentration of black cardamom extract is utilized as a capping and reducing agent. The decision to use this extract can be justified because it has a quick reducing capacity. Scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), Dynamic Light Scattering (DLS), and Fourier-transform infrared spectroscopy (FT-IR) have all been used to analyze the NPs. Furthermore, healthy cells (PBMCs) and the Acute Promyelocytic Leukemia cell lines (NB4 and HL-60) were treated to varied concentrations of ZnO NPs for 24 and 48 h. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) test was then used to determine the cell viability. Oxidative and ferroptosis markers were evaluated using commercial kits. Gene expression and cell death were measured using qRT-PCR and flow cytometry. Also, the binding energy and van der Waals interactions of ZnO NP-protein complexes were calculated using molecular docking. On leukemic cells, ZnO NPs displayed growth-inhibiting effects in a time and dose-dependent manner. By considerably boosting lipid-ROS, intracellular iron, ACSL4, and p53 while significantly lowering GSH and GPx activity levels, as well as SLC7A11 and GPx4 mRNA, the ZnO NPs accelerated the ferroptotic cell death. On the other hand, ZnO NPs showed no toxicity to healthy cells. So, based on our research, synthesized ZnO NPs can induce ferroptotic cell death in leukemic cells.

YAP1 inhibits RSL3-induced castration-resistant prostate cancer cell ferroptosis by driving glutamine uptake and metabolism to GSH

High levels of YAP1 and ferroptosis activation in castration-resistant prostate cancer (CRPC) can inhibit CRPC progression and improve its sensitivity toward chemotherapeutics drugs. However, whether YAP1 regulates ferroptosis in CRPC cells and the underlying mechanisms are unknown. The protein levels of YAP1, SLC1A5, and GLS1 in benign prostatic hyperplasia (BPH), prostate cancer (PCa) that did not progress to CRPC, and CRPC tissue samples were evaluated using western blotting. In PC-3 and DU-145 cells, YAP1 overexpression vector, small-interfering RNA, specific inhibitor verteporfin, ferroptosis-inducer RSL3, SLC1A5-inhibitor V-9302, and GLS1-inhibitor CB-839 were used. Immunofluorescence, flow cytometry, dual-luciferase reporter gene, and related kits were used to investigate the effect of YAP1 on the ferroptosis activity in CRPC cells and its underlying mechanisms. YAP1 promoted extracellular glutamine uptake and subsequent production of glutamate and glutathione (GSH), and increases the GPX4 activity. For the activation of ferroptosis by RSL3, YAP1 decreased the levels of reactive oxygen species, malondialdehyde, and lipid peroxidation, and the proportion of dead cells. Mechanistically, YAP1 promoted the expression of SCL1A5 and GLS1 and further increased the GSH levels and GPX4 activity. Thus, inhibiting SLC1A5 or GLS1 activity could alleviate the antagonistic effect of YAP1 on the ferroptosis of RSL3-induced CRPC cells. In CRPC, the YAP1 level is high, which enters the nucleus and promotes the expressions of SLC1A5 and GLS1, thereby promoting cellular glutamine uptake and metabolism to generate glutamate and further synthesizing GSH, increasing GPX4 activity, improving cellular antioxidant capacity, and inhibiting cell death.

Chrysophanol improves memory impairment and cell injury by reducing the level of ferroptosis in Aβ25-35 treated rat and PC12 cells.

Alzheimer's disease (AD) is a common age-related chronic and neurodegenerative disease that has become a global health problem. AD pathogenesis is complex, and the clinical efficacy of commonly used anti-AD drugs is suboptimal. Recent research has revealed a close association between AD-induced damage and the activation of ferroptosis signaling pathways. Chrysophanol (CHR) the principal medicinal component of Rhubarb, has been reported to have anti-AD effects and can reduce ROS levels in AD-damaged models. AD has been linked to the activation of ferroptosis signaling pathways, which has an important feature of higher levels of reactive oxygen species (ROS). Therefore, the present study explored whether CHR had an anti-AD effect by regulating the ferroptosis levels in AD injury models. Morris water maze, novel object recognition test, Y-maze test, Hematoxylin-eosin (H&E) staining, western blotting, ROS measurement, GPx activity measurement, LPO measurement, transmission electron microscopy, live/dead cell staining were used to investigate the changes in spatial memory level and ferroptosis level in AD model, and the intervention effect of CHR. CHR improved the spatial memory level of AD rat models, reduced the level of hippocampal neuron damage, and improved the survival rate of PC12 cells damaged by β-amyloid (Aβ). Meanwhile, CHR increased glutathione peroxidase-4 (GPX4) protein expression, GPx activity, and GSH, decreased ROS and LPO levels in AD rat models and Aβ-damaged PC12 cells, and improved mitochondrial pathological damage. Our findings suggest that CHR may play a protective role in AD injury by lowering ferroptosis levels, which may provide a potential pathway for developing drugs for AD. However, the mechanism of CHR's role requires further investigation.