GPx Activity Research Articles

Camptothecin Sensitizes Hepatocellular Carcinoma Cells to Sorafenib- Induced Ferroptosis Via Suppression of Nrf2

Sorafenib is a potent inducer of ferroptosis used to manage hepatocellular carcinoma (HCC). The ferroptosis induced by sorafenib activates the p62–Keap1–Nrf2 pathway. Abnormal activation of Nrf2 reduces sorafenib’s efficiency and ferroptosis action and induces sorafenib’s resistance. Consequently, our study tried to study the effect of a novel combination of sorafenib and Camptothecin (CPT, Nrf2 inhibitor) to improve sorafenib’s ferroptosis action and reduce sorafenib resistance in the treatment of HCC. We evaluated the efficacy of sorafenib and/or CPT using HepG2 and Huh7 cell lines. MTT assay evaluated the anti-proliferation effects. The combination index (CI) and dose reduction index (DRI) were calculated using Isobologram analysis. Malondialdehyde (MDA), total antioxidant capacity (TAC), iron concentration, glutathione peroxidase (GPX4), and glutathione reductase (GR) activity assays were used to determine the ferroptosis action of drugs. Western blot was used to investigate the expression of the implicated proteins. Bioinformatics tools were used to determine the correlation between these proteins. Finally, the HPLC technique is used to measure cellular drug uptake. Our results revealed a strong synergism between sorafenib and CPT. The synergetic combination significantly increases lipid peroxidation and iron concentration, decreases TAC, GPX4 and GR activity, and reduces the expression of both Nrf2 and SLC7A11. The downregulation of Nrf2 expression has a vital role in the reduction of resistance mediators to sorafenib against HCC cells like (p62, MT1G, and ABCG2) and improves the cellular uptake of sorafenib. The current study provided evidence that Nrf2 inhibition by CPT improves sorafenib’s sensitivity and reduces sorafenib’s resistance via the augmentation of sorafenib’s ferroptosis action.

Immune Redox Modulation Effects of Non-Electrolyzed Hypochlorous Acid Water on Helicobacter pylori-Infected C57BL/6 Mouse Model

Recently, non-electrolyzed HOCl water has gained the attention of researchers as a new disinfecting agent owing to its high sterilization power, easy accessibility, and safety. Non-electrolyzed HOCl water was developed through mixing at a specific ratio based on hypochlorite and mineral supplements, which revealed a high oxidizing power. In this study, we investigated the effects of non-electrolyzed HOCl water on Helicobacter pylori (H. pylori) infection in C57BL/6 mice over 10 weeks. Mice were divided into three groups: normal control (NC) group supplied with purified water (PW) without infection, PW + H. pylori group supplied with PW after H. pylori infection, and HOCl + H. pylori group supplied with HOCl after H. pylori infection. Our findings demonstrated that the HOCl + H. pylori group greatly inhibited WBC and its differential counts, including total white blood cell (WBC), neutrophils, lymphocytes, monocytes, and eosinophils, when compared to the PW + H. pylori group. Accordingly, the amount of reactive oxygen species and calcium activity significantly decreased in the HOCl + H. pylori group compared to the PW + H. pylori group in both serum and stomach lysates. In contrast, HOCl water treatment enhanced GPx activity compared to PW treatment after H. pylori infection in both serum and stomach lysates. Accordingly, the levels of granulocyte-macrophage colony-stimulating factor, IL-1β, and TNF-α cytokine levels were significantly decreased in the HOCl + H. pylori group compared to those in the PW + H. pylori group in the stomach lysate; however, there was no significant difference in serum. In addition, the expression levels of Bax, MMP-3, MMP-9, and TLR-4 were found to decrease after HOCl water treatment, whereas the expression level of Bcl-2 was found to be enhanced after HOCl water treatment in the stomach lysate. Taken together, our results suggest that drinking non-electrolyzed HOCl water has positive anti-oxidative, anti-inflammatory, and anti-apoptotic effects in H. pylori-infected mice through redox and immune regulation.

Comparative biochemical and molecular responses of biotransformation and antioxidant systems in three species of Crassostrea (Sacco, 1897) oysters exposed to chrysene

Chrysene (CHR) is among the most persistent polycyclic aromatic hydrocarbons (PAH) in water and a priority compound for pollutants monitoring, due to its carcinogenic, mutagenic and genotoxic potential. Aquatic animals exposed to CHR may present alterations of biomarkers involved in the biotransformation and oxidative stress-related parameters. The aim of this study was to investigate differences in antioxidant and biotransformation (phase I and II) systems of Crassostrea gigas, C. gasar and C. rhizophorae and its effects resulting from CHR exposure. Adult oysters of these species were exposed to 10 μg L−1 of CHR for 24 h and 96 h. In gills, the transcripts CYP1-like, CYP2-like, CYP2AU1-like, GSTO-like, MGST-like, SULT-like were evaluated after 24 h of exposure. The activity of SOD, CAT, GPx, GR and G6PDH were analyzed in gills and digestive glands after 96 h of exposure. CHR bioaccumulated in tissues. Differences in the remaining levels of CHR in water after 96 h were observed in aquaria containing C. gigas or C. gasar oysters and may be associated to the different filtration rates between these species. Downregulate of biotransformation genes were observed in gills of C. gasar (CYP2AU1-like and GSTO-like) and C. rhizophorae (CYP1-like1, CYP2-like, MGST-like and SULT-like), suggesting that biotransformation responses may be species-specific. Differential activity of antioxidant enzymes were observed in gills and digestive gland of oysters exposed to CHR. Biochemical responses suggested that C. gigas and C. gasar are more responsive to CHR. Differential responses observed among the three Crassostrea species can be related to evolutionary differences, ecological niches and adaptation to environment.

The Trace Element Concentrations and Oxidative Stress Parameters in Afterbirths from Women with Multiple Pregnancies.

The aim of this study was to evaluate the intensity of oxidative stress by measuring the concentrations of lipid peroxidation products (LPO) in fetal membrane, umbilical cord, and placenta samples obtained from women with multiple pregnancies. Additionally, the effectiveness of protection against oxidative stress was assessed by measuring the activity of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR). Due to the role of iron (Fe), copper (Cu), and zinc (Zn) as cofactors for antioxidant enzymes, the concentrations of these elements were also analyzed in the studied afterbirths. The obtained data were compared with newborn parameters, selected environmental factors, and the health status of women during pregnancy to determine the relationship between oxidative stress and the health of women and their offspring during pregnancy. The study involved women (n = 22) with multiple pregnancies and their newborns (n = 45). The Fe, Zn, and Cu levels in the placenta, umbilical cord, and fetal membrane were determined using inductively coupled plasma atomic emission spectroscopy (ICP-OES) using an ICAP 7400 Duo system. Commercial assays were used to determine SOD, GPx, GR, CAT, and LPO activity levels. The determinations were made spectrophotometrically. The present study also investigated the relationships between trace element concentrations in fetal membrane, placenta, and umbilical cord samples and various maternal and infant parameters in women. Notably, a strong positive correlation was observed between Cu and Zn concentrations in the fetal membrane (p = 0.66) and between Zn and Fe concentrations in the placenta (p = 0.61). The fetal membrane Zn concentration exhibited a negative correlation with shoulder width (p = -0.35), while the placenta Cu concentration was positively correlated with placenta weight (p = 0.46) and shoulder width (p = 0.36). The umbilical cord Cu level was positively correlated with head circumference (p = 0.36) and birth weight (p = 0.35), while the placenta Fe concentration was positively correlated with placenta weight (p = 0.33). Furthermore, correlations were determined between the parameters of antioxidative stress (GPx, GR, CAT, SOD) and oxidative stress (LPO) and the parameters of infants and maternal characteristics. A negative correlation was observed between Fe and LPO product concentrations in the fetal membrane (p = -0.50) and placenta (p = -0.58), while the Cu concentration positively correlated with SOD activity in the umbilical cord (p = 0.55). Given that multiple pregnancies are associated with various complications, such as preterm birth, gestational hypertension, gestational diabetes, and placental and umbilical cord abnormalities, research in this area is crucial for preventing obstetric failures. Our results could serve as comparative data for future studies. However, we advise caution when interpreting our results, despite achieving statistical significance.

Evaluating the Effects of Probiotic Supplementation on Neuropathic Pain and Oxidative Stress Factors in an Animal Model of Chronic Constriction Injury of the Sciatic Nerve

Introduction: Neuropathic pain is a common and painful somatosensory nervous system disease, and its treatment remains a medical challenge. Evidence demonstrates that gut microbiota alters in neuropathic pain and, therefore, improvement of the gut flora may affect the disease. The present study aimed to evaluate the antinociceptive effect of probiotics in neuropathic pain and oxidative biomarkers’ responsiveness to the probiotic treatment. Methods: Using chronic constriction injury (CCI) of the rats' sciatic nerve, neuropathic pain was induced. Investigating the analgesic effect of the probiotics mixture, 40 male rats were randomly assigned to 4 groups (n=10 for each): Sham-operated (SM), and CCI model rats orally received 1 mL saline (CS), or 100 mg/kg gabapentin (CG) or 1 mL probiotics mixture (CP) Lactobacillus plantarum, Lactobacillus delbrueckii, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Bifidobacterium bifidum (109 CFU of each) daily. Using behavioral tests, the pain was assessed on days 1, 4, 7, 14, and 21 of the study. Finally, the biochemical evaluation of sciatic nerve tissue was done. Results: Probiotics decreased cold and mechanic allodynia and thermal hyperalgesia. Reducing lipid peroxidation levels and increasing total antioxidant capacity, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were also significant in the probiotics group. Conclusion: These findings suggest that probiotics have analgesic effects on the CCI model of neuropathic pain via increasing the antioxidant capacity of the rats’ sciatic nerve.

The effects of ethanol extract of Punica granatum L. peel on the testis damage induced by diabetes in rats

In this study, it was aimed to determine the effect of ethanol extract of Punica granatum L. peel (PGE) on oxidative stress and histopathological values in blood and testis tissue in rats with diabetes. In present study used twenty-eight male Sprague Dawley rats were randomly divided into four equal groups containing of seven rats per group. Group 1; peros physiological saline to the rat, Group 2; STZ 60 mg/kg/IP single dose, Group 3; PGE 10 mg/kg/20days/peros, Group 4; STZ as 60 mg/kg/IP + PGE 10 mg/kg/20days/peros. After the end of the experimental procedure, the rats were sacrificed, blood and testicular tissues were taken, and biochemical and histopathological examinations were performed. The administration of PGE was shown that the activities of CAT, SOD, GPx and GSH increased and the levels of MDA decreased in diabetic rats. Oral administration of PGE reduced the levels of LPO and improved the antioxidant activity in plasma and testis tissues while compared with the Groups 4. Histopathological examination of testicular tissues in the Group 2 is revealed edema in the intertubular spaces, thinning of the tubule walls due to diminished spermatocytes in the walls of the seminiferous tubules and severe degenerative and necrotic changes in spermatocytes. These changes were found to be very mild in Group 4. According to immunohistochemical findings, in Group 2, caspase 3 expression was intensely expressed in spermatocytes. As a result, it was observed that Punica granatum L. peel extract strengthened antioxidant defense and reduced oxidative stress in diabetic rats.

Alteration in the Antioxidant Enzymes Activities as Potential Biomarkers for Identification of Stress Caused by Afidopyropen Intoxication in Cyprinus Carpio.

This study comparatively investigated the afidopyropen-induced oxidative stress in the fish Cyprinus carpio which is mainly focused on some biochemical parameters such as SOD, CAT, GPx, LPO, ALT, ALP, and GGT activities. Fishes were exposed to different durations (1, 10, 20, and 30 days) in a semi-static method at a sub-lethal concentration of LC50 value. Results show that the duration elicited higher levels of LPO, ALT, and ALP. The LPO levels in the blood were higher in 30 days of exposed fish and this led to significant changes in GPx. The fish exposed for 1 day had found the least increment of 0.71%, and 2.08% in ALT, and ALP activity respectively. The assessment of CAT, GPx, and GGT they were decreased by sub-lethal concentration i.e., 0.2 mg/L of afidopyropen for 10, 20, and 30 days. The results conclude that the afidopyropen has a negative effect on the fish Cyprinus carpio and these differences are evidenced by sensitivity to afidopyropen in the aquatic environment.

Different cold tolerances among three strains of large yellow croaker: related to antioxidant defense and energy metabolism

The aim of this study was to compare low-temperature tolerances in different strains of large yellow croaker. Dai Qu (DQ), Min-Yue Dong (MY), and Quan Zhou (NZ) strains of large yellow croaker were subjected to cold stress (8.6°C) for 12h, 24h, 48h, and 96h. Survival rate, histological observation, and antioxidant and energy metabolism indicators were determined. The results showed that compared with the DQ group and MY group, NZ group aggravated hepatic structure, enhanced ROS, lactate, and anaerobic metabolism (PK gene expression and activity), while inhibited ATP, GSH, antioxidant enzymes (mRNA levels and activities of SOD, GPx, and CAT), and aerobic metabolism enzymes (mRNA levels and activities of F-ATPase, SDH, and MDH), indicating the reduction of cold tolerance in the NZ group was closely correlated with the decrement of antioxidative capacity and energy metabolism efficiency. Nrf2 and AMPK gene expressions were correlated with antioxidant and energy metabolism mRNA levels, respectively, suggesting Nrf2 and AMPK might participate in the modulation of target genes during the cold-stress adaptation. In conclusion, low temperature tolerance of fish depended on the antioxidant defense and energy metabolism efficiency, which contributes to understanding the underlying mechanisms of cold adaptation in large yellow croaker.

The Co-Occurrence of T-2 Toxin, Deoxynivalenol, and Fumonisin B1 Activated the Glutathione Redox System in the EU-Limiting Doses in Laying Hens.

Different mycotoxins in feed lead to combined exposure, increasing adverse effects on animal health. Trichothecene mycotoxins have been associated with inducing oxidative stress, which is neutralized by the glutathione system within the antioxidant defense, depending on the dose and duration of exposure. T-2 toxin, deoxynivalenol (DON), and fumonisin B1 (FB1) are commonly found in feed commodities simultaneously. In the present study, the intracellular biochemical and gene expression changes were investigated in the case of multi-mycotoxin exposure, focusing on certain elements of the glutathione redox system. In a short-term feeding trial, an in vivo study was performed with low (EU-proposed) doses: T-2/HT-2 toxin: 0.25 mg; DON/2-AcDON/15-AcDON.: 5 mg; FB1: 20 mg/kg feed, and high doses (twice the low dose) in laying hens. The multi-mycotoxin exposure affected the glutathione system; GSH concentration and GPx activity was higher in the liver in the low-dose group on day 1 compared to the control. Furthermore, the gene expression of antioxidant enzymes increased significantly on day 1 in both exposure levels compared to the control. The results suggest that when EU-limiting doses are applied, individual mycotoxins may have a synergistic effect in the induction of oxidative stress.

The ferroptosis inducing compounds RSL3 and ML162 are not direct inhibitors of GPX4 but of TXNRD1

Ferroptosis is defined as cell death triggered by iron-dependent lipid peroxidation that is preventable by antioxidant compounds such as ferrostatin-1. Endogenous suppressors of ferroptosis include FSP-1 and the selenoprotein GPX4, the latter of which directly enzymatically reduces lipid hydroperoxides. Small molecules that trigger ferroptosis include RSL3, ML162, and ML210; these compounds are often used in studies of ferroptosis and are generally considered as GPX4 inhibitors. Here, we found that RSL3 and ML162 completely lack capacity of inhibiting the enzymatic activity of recombinant selenoprotein GPX4. Surprisingly, these compounds were instead found to be efficient inhibitors of another selenoprotein, TXNRD1. Other known inhibitors of TXNRD1, including auranofin, TRi-1 and TRi-2, are also efficient inducers of cell death but that cell death could not be suppressed with ferrostatin-1. Our results collectively suggest that prior studies using RSL3 and ML162 may need to be reevaluated in the context of ferroptosis with regards to additional enzyme targets and mechanisms of action that may be involved.

The combined effect of zinc oxide nanoparticles and milrinone on acute renal ischemia/reperfusion injury in rats: Potential underlying mechanisms

AimTo investigate the efficacy of zinc oxide nanoparticles (ZnO-NPs) and/or milrinone (MIL) on renal ischemia/reperfusion injury (I/RI) in rats and their possible underlying mechanisms. Materials and methodsForty-eight adult male Sprague-Dawley albino rats were randomly assigned into six equal-sized groups (n = 8): normal control, sham-operated, I/R group (45 min/24 h), ZnO-NPs group (10 mg/kg i.p.), MIL group (0.5 mg/kg i.p.), and ZnO-NPs + MIL group in the same previous doses. Key findingsIn comparison to the I/R-operated group, administration of either ZnO-NPs or MIL significantly decreased serum creatinine and urea concentrations, and renal vascular permeability (p < 0.05). The oxidative stress was significantly declined, as evidenced by increased GPx, CAT, and SOD activities and decreased MDA and NO concentrations. Renal expressions of TNF-α, NF-κB, KIM-1, NGAL, and caspase-3 decreased significantly, while Nrf2 increased significantly. Histopathology investigation revealed improvement with minimal renal lesions and fibrosis after ZnO-NPs or MIL treatments. The combined treatments synergistically improved the studied parameters more than either treatment alone. These findings were validated by molecular modeling, which revealed that MIL inhibited TNF-α, NF-kB, caspase-3, KIM-1 and NGAL. SignificanceBoth ZnO-NPs and MIL exerted cytoprotective effects against acute renal I/RI, and a combination of both was found to be even more effective. This renoprotective effect is suggested to be mediated through activation of Nrf2 and the prevention of the NF-κB activation-induced oxidative stress and inflammation, which may strengthen the potential role of ZnO-NPs or MIL in renal I/RI protection during surgical procedures.

The cardioprotective effect of human glucagon-like peptide-1 receptor agonist (semaglutide) on cisplatin-induced cardiotoxicity in rats: Targeting mitochondrial functions, dynamics, biogenesis, and redox status pathways.

The cardiotoxic effect of chemotherapeutic agents as cisplatin has become a major issue recently. Interference with mitochondrial dynamics, biogenesis, redox status, and apoptosis are the most possible underlying mechanisms. Semaglutide is a human glucagon-like peptide-1 receptor agonist (GLP-1R), which is used primarily for the treatment of DM. Various recent studies have investigated (GLP-1R) role in cardiovascular diseases due to antiapoptotic and antioxidant effects. The current study aimed to investigate the curative role of semaglutide's against cisplatin- induced cardiotoxicity and its relation to mitochondrial functions, dynamics, biogenesis, apoptosis, and redox status pathways. The study included 30 male rats divided into three groups: control, cisplatin-induced cardiotoxicity, and cisplatin-induced cardiotoxicity treated with semaglutide. At the end of the experiment heart index, serum cardiotoxicity markers, SOD, GPX activities and H2 O2 level were estimated. Mitochondrial transmembrane potential, complex I and citrate synthase enzyme activities, ATP level, Mfn2 in addition to PGC-1 α levels were assessed as biogenesis markers. Mitophagy markers PINK1 and Parkin mRNA gene expression were estimated. Histopathological examination of cardiac muscles of all studied groups and immunoassay of P53 and caspase 3 in cardiac tissue were examined to assess apoptosis. Cisplatin has disturbed mitochondrial function and dynamics, dysregulate redox status and induced mitophagy and apoptosis, in the other hand semaglutide treatment has normalized dysregulated mitochondrial function and dynamics, redox status and suppressed mitophagy and apoptosis. Semaglutide has ameliorative effect against cisplatin- induced cardiotoxicity via modulation of mitochondrial functions, dynamics, biogenesis, apoptosis, and redox status pathways.

Polysaccharides extracted from mulberry fruits (Morus nigra L.): antioxidant effect of ameliorating H2O2-induced liver injury in HepG2 cells

BackgroundMori Fructus is an economical and readily available traditional Chinese medicine and food. Polysaccharides in Mori Fructus have clear antioxidant activity and have been found to alleviate oxidative stress (OS)-induced liver damage in experimental studies. The mechanism of regulation of cellular antioxidant activity by mulberry polysaccharides has been suggested to be Nrf2, but it is not clear whether the Nrf2 pathway is mediated by activation of other targets, and the exact process of effects in hepatocytes has yet to be elucidated.MethodsIn this study, the basic characterization of total polysaccharides extracted from mulberry fruits (Morus nigra Linn.) was analyzed. A model of oxidative damage induced by H2O2 in HepG2 cells was established. The levels of cellular oxidation-related markers, including ROS, SOD and Gpx, were then examined. Furthermore, Q-PCR and Western-blot were used to detect the expression of genes and proteins related to the PI3K/Akt-mediated Nrf2 signaling pathway.ResultsThe results showed that a total mulberry polysaccharides (TMP) has a molecular weight of 57.5 kDa with a pyranose ring mainly composed of glucose (48.81%), galactose (22.79%) and mannose (18.2%). TMP reduced the accumulation of ROS in HepG2 cells after H2O2 treatment and modulated the activity of SOD and Gpx. Q-PCR and Western-blot showed that TMP could up-regulate the expression of p-PI3K, p-AKT, Nrf2, NQO1 and HO-1.ConclusionsThis study demonstrates that TMP can reduce ROS accumulation in H2O2-treated HepG2 cells and restore cell viability by activating the PI3K/AKT-mediated Nrf2 pathway. TMP may be a potent antioxidant agent that could slow down oxidative damage to the liver.

Tetraclinis articulata essential oil emulsion use as alternative to chemical fungicide to control tomato grey mould disease

ABSTRACT Tetraclinis articulata essential oil proved to be effective in controlling tomato grey mould, so we would investigate its effect on some tomato defense mechanisms. The pretreatment of Botrytis cinerea infected tomato plants with TAEO emulsion enhanced the activity of antioxidant enzymes activity SOD, CAT, APX, and GPX, and total polyphenols content and it decreased IC50 of free radical-scavenging activity and H2O2 content. Results showed amelioration in antioxidant status in TAEO emulsion treated and B. cinerea infected plants indicating that treatment decreased infection in tomato plants. The qRT-PCR analysis of defense genes expression Chitinase SlChi, transcription factors SlWRKY and SlAP2/ERF, Lipoxygenase SlLOX, and Thioredoxin SlTRX showed that they were up-regulated as early as 12 hpi sustained with a second increase at 48 hpi in TAEO emulsion pretreated and infected plants. These results suggest the potential use of TAEO emulsion as natural product to induce tomato antioxidant status and activate defense genes.

Association Between Parameters of Cortisol Metabolism, Biomarkers of Minerals (Zinc, Selenium, and Magnesium), and Insulin Resistance and Oxidative Stress in Women with Obesity.

This is a cross-sectional study with women divided into a group of those with obesity (n = 80) and a control group (n = 94). Statistical analysis was conducted using the SPSS program. There were high values of GPx and TBARS and reduced values of SOD in women with obesity compared to the control group. Obese women showed increased concentrations of cortisol in serum and urine as well as hypozincemia, hyposelenemia, and hypomagnesemia and increased urinary excretion of these minerals. There was a negative correlation between the cortisol/cortisone ratio and erythrocyte zinc and selenium concentrations and a significant positive correlation between GPx and SOD activity and erythrocyte and plasma concentrations of zinc and selenium. The results of the study suggest the influence of adiposity on the increase in cortisol concentrations and the role of this hormone in the compartmentalization of the minerals zinc, selenium, and magnesium. However, the association study does not allow identifying the impact of such action on the antioxidant defense system and insulin sensitivity.

Impacts of Deoxygenation and Hypoxia on Shark Embryos Anti-Predator Behavior and Oxidative Stress.

Climate change is leading to the loss of oxygen content in the oceans and endangering the survival of many marine species. Due to sea surface temperature warming and changing circulation, the ocean has become more stratified and is consequently losing its oxygen content. Oviparous elasmobranchs are particularly vulnerable as they lay their eggs in coastal and shallow areas, where they experience significant oscillations in oxygen levels. Here, we investigated the effects of deoxygenation (93% air saturation) and hypoxia (26% air saturation) during a short-term period (six days) on the anti-predator avoidance behavior and physiology (oxidative stress) of small-spotted catshark (Scyliorhinus canicula) embryos. Their survival rate decreased to 88% and 56% under deoxygenation and hypoxia, respectively. The tail beat rates were significantly enhanced in the embryos under hypoxia compared to those exposed to deoxygenation and control conditions, and the freeze response duration showed a significant opposite trend. Yet, at the physiological level, through the analyses of key biomarkers (SOD, CAT, GPx, and GST activities as well as HSP70, Ubiquitin, and MDA levels), we found no evidence of increased oxidative stress and cell damage under hypoxia. Thus, the present findings show that the projected end-of-the-century deoxygenation levels elicit neglectable biological effects on shark embryos. On the other hand, hypoxia causes a high embryo mortality rate. Additionally, hypoxia makes embryos more vulnerable to predators, because the increased tail beat frequency will enhance the release of chemical and physical cues that can be detected by predators. The shortening of the shark freeze response under hypoxia also makes the embryos more prone to predation.

Antioxidant potentialities and gastroprotective effect of Reichardia picroides extracts on Ethanol/HCl induced gastric ulcer rats

ABSTRACT The goal of this study was to determine for the first time the polyphenol content, antioxidant, and gastroprotective properties of the roots and leaves of Reichardia picroides. TPC considerably varied as a function of organs and solvent nature and ranged from 50 to 284.80 mg GAE/g DW. Leaves exhibited the highest amount of phenolics by using acetone 70%, the same tendency was observed for antioxidant activity. Besides, in vivo gastro-protective effects following HCl/EtOH-induced ulcer models displayed that roots extract at a high dose (500 mg) seemed to be the best performing extract with a decrease of ulceration index (UI) and an increase in the percentage of protection (PP), SOD, CAT, and GPX activities. All these data have been proved with principal component analysis (PCA). Overall, the results indicated that R. picroides could be considered a valuable source of natural compounds, which are beneficial for human health.

Effect of deferoxamine and ferrostatin-1 on salivary gland dysfunction in ovariectomized rats.

The mechanism underlying xerostomia after menopause has not yet been fully elucidated. This study aimed to investigate the mechanism of xerostomia and the effect of the ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (FER) on salivary gland dysfunction in a postmenopausal animal model. Twenty-four female Sprague-Dawley rats were randomly divided into four groups: a SHAM group (n = 6, sham-operated rats), an OVX group (n = 6, ovariectomized rats), an FER group (n = 6, ovariectomized rats injected intraperitoneally with FER), and a DFO group (n = 6, ovariectomized rats injected intraperitoneally with DFO). GPX4 activity, iron accumulation, lipid peroxidation, inflammation, fibrosis, and salivary gland function were analyzed. Recovery of GPX4 activity and a decrease in iron accumulation and cytosolic MDA + HAE were observed in the DFO group. In addition, collagen I, collagen III, TGF-β, IL-6, TNF-α, and TGF-β levels were decreased in the DFO group compared to the OVX group. Recovery of GPX4 activity and the morphology of mitochondria, and reduction of cytosolic MDA + HAE were also observed in the FER group. In addition, decreased expression of inflammatory cytokines and fibrosis markers and increased expression of AQP5 were observed in both the DFO and FER groups. Postmenopausal salivary gland dysfunction is associated with ferroptosis, and DFO and FER may reverse the postmenopausal salivary gland dysfunction after menopause. DFO and FER are hence considered promising treatments for postmenopausal xerostomia.

Dietary Soybean Lecithin Improves Growth, Immunity, Antioxidant Capability and Intestinal Barrier Functions in Largemouth Bass Micropterus salmoides Juveniles.

This study evaluated the effects of dietary soybean lecithin (SBL) on the growth, haematological indices, immunities, antioxidant capabilities, and inflammatory and intestinal barrier functions because little information of dietary SBL could be obtained in juvenile largemouth bass (Micropterus salmoides). The fish were fed identical diets except for SBL added at 0, 2, 4 and 8%. It was found that 4 and 8% SBL significantly increased fish weight gain and daily growth rate (p < 0.05), while 4% SBL was optimal for enhancing RBC, HGB, PLT, MCV, MCH, WBC and MON in blood, and ALB and ALP in serum (p < 0.05). SBL (4%) also significantly elevated the antioxidant enzymes activities of T-SOD, CAT, GR, GPx, GST and T-AOC and GSH contents; increased mRNA transcription levels of Nrf2, Cu/Zn-SOD, CAT, GR, GST3 and GPx3; and decreased MDA contents. Keap1a and Keap1b levels were markedly down-regulated (p < 0.05). SBL (4%) significantly enhanced levels of the immune factors (ACP, LZM and C3) and the mRNA expression levels of innate immune-related genes (C3, C4, CFD, HEPC and MHC-I) compared with the control groups (0%) (p < 0.05). SBL (4%) significantly increased IgM and T-NOS in the intestine (p < 0.05) and significantly decreased levels of TNF-α, IL-8, IL-1β and IFN-γ and increased TGF-β1 at both transcription and protein levels in the liver and intestine (p < 0.05). The mRNA expression levels of MAPK13, MAPK14 and NF-κB P65 were significantly decreased in the intestine in the 4% SBL groups (p < 0.05). Histological sections also demonstrated that 4% SBL protected intestinal morphological structures compared with controls. This included increased intestinal villus height and muscular thickness (p < 0.05). Furthermore, the mRNA expression levels of the intestinal epithelial cell tight junction proteins (TJs) (ZO-1, claudin-3, claudin-4, claudin-5, claudin-23 and claudin-34) and mucin-5AC were significantly up-regulated in the 4% SBL groups compared with the controls (p < 0.05). In conclusion, these results suggested that 4% dietary SBL could not only improve growth, haematological indices, antioxidant capabilities, immune responses and intestinal functions, but also alleviate inflammatory responses, thereby providing reference information for the feed formulations in cultured largemouth bass.

Interdependencies of Gene Expression and Function between Two Redox Enzymes and REG Family Proteins in Murine Pancreatic Islets and Human Pancreatic Cells.

Our laboratory previously revealed that regenerating islets-derived protein 2 (REG2) was diminished in pancreatic islets of glutathione peroxidase-1-overexpressing mice (Gpx1-OE). It remained unknown if there is an inverse relationship between the expression and function of all Reg family genes and antioxidant enzymes in the pancreatic islets or human pancreatic cells. This research was to determine how altering the Gpx1 and superoxide dismutase-1 (Sod1) genes alone or together (dKO) affected the expression of all seven murine Reg genes in murine pancreatic islets. In Experiment 1, Gpx1-/-, Gpx1-OE, their wild-type (WT), Sod1-/-, dKO, and their WT (male, 8-wk old, n = 4-6) were fed a Se-adequate diet and their islets were collected to assay the mRNA levels of Reg family genes. In Experiment 2, islets from the six groups of mice were treated with phosphate-buffered saline (PBS), REG2, or REG2 mutant protein (1 µg/mL), and/or GPX mimic (ebselen, 50 µM) and SOD mimic (copper [II] diisopropyl salicylate, CuDIPS, 10 µM) for 48 h before the proliferation assay using bromodeoxyuridine (BrdU). In Experiment 3, human pancreatic cells (PANC1) were treated with REG2 (1 µg/mL) and assayed for REG gene expression, GPX1 and SOD1 activities, viability, and responses to Ca2+. Compared with the WT, knockouts of Gpx1 and/or Sod1 up-regulated (p < 0.05) the mRNA levels of most of the murine Reg genes in islets whereas the Gpx1 overexpression down-regulated (p < 0.05) Reg mRNA levels. REG2, but not the REG2 mutant, inhibited islet proliferation in Gpx1 or Sod1-altered mice. Such inhibition was abolished by co-incubation the Gpx1-/- islets with ebselen and the Sod1-/- islets with CuDIPS. Treating PANC1 cells with murine REG2 protein induced expression of its human orthologue REG1B and three other REG genes, but decreased SOD1 and GPX1 activities and cell viability. In conclusion, our results revealed an interdependence of REG family gene expression and/or function on intracellular GPX1 and SOD1 activities in murine islets and human pancreatic cells.