Long-term detraining reverses the improvement of lifelong exercise on skeletal muscle ferroptosis and inflammation in aging rats: fiber-type dependence of the Keap1/Nrf2 pathway.

We investigated the effects of lifelong aerobic exercise and 8 months of detraining after 10 months of aerobic training on circulation, skeletal muscle oxidative stress, and inflammation in aging rats. Sprague-Dawley rats were randomly assigned to the control (CON), detraining (DET), and lifelong aerobic training (LAT) groups. The DET and LAT groups began aerobic treadmill exercise at the age of 8 months and stopped training at the 18th and 26th month, respectively; all rats were sacrificed when aged 26 months. Compared with CON, LAT remarkably decreased serum and aged skeletal muscle 4-hydroxynonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. Superoxide dismutase 2(SOD2) levels were higher in the LAT group than in the CON group in skeletal muscle. However, DET remarkably decreased SOD2 protein expression and content in the skeletal muscle and increased malondialdehyde (MDA) level compared with LAT. Compared with LAT, DET remarkably downregulated adiponectin and upregulated tumor necrosis factor alpha (TNF-α) expression, while phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and 70-kDa ribosomal protein S6 kinase (P70S6K) protein expression decreased, and that of FoxO1 and muscle atrophy F-box (MAFbX) proteins increased in the quadriceps femoris. Adiponectin and TNF-α expression in the soleus muscle did not change between groups, whereas that of AKT, mammalian target of rapamycin (mTOR), and P70S6K was lower in the soleus in the DET group than in that in the LAT group. Compared with that in the LAT group, sestrin1 (SES1) and nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression in the DET group was lower, whereas Keap1 mRNA expression was remarkably upregulated in the quadriceps femoris. Interestingly, the protein and mRNA levels of SES1, Nrf2, and Keap1 in soleus muscle did not differ between groups. LAT remarkably upregulated ferritin heavy polypeptide 1(FTH), glutathione peroxidase 4(GPX4), and solute carrier family 7member 11 (SLC7A11) protein expression in the quadriceps femoris and soleus muscles, compared with CON. However, compared with LAT, DET downregulated FTH, GPX4, and SLC7A11 protein expression in the quadriceps femoris and soleus muscles. Long-term detraining during the aging phase reverses the improvement effect of lifelong exercise on oxidative stress, inflammation, ferroptosis, and muscle atrophy in aging skeletal muscle. The quadriceps femoris is more evident than the soleus, which may be related to the different changes in the Keap1/Nrf2 pathway in different skeletal muscles.

Abamectin induced brain and liver toxicity in carp: The healing potential of silybin and potential molecular mechanisms.

Abamectin (ABM) abuse contaminated aquatic environment and posed a potential threat to fish health as well as public safety. Silybin (SIL), a flavonoid, has been widely used as a novel feed additive to promote fish health. This research was to explore the potential antagonistic mechanism between ABM and SIL on brain and liver toxicity was investigated in common carp. Sixty carp were divided into four groups at random: the Control group, the SIL group, the ABM group, and ABM + SIL group. This experiment lasted for 30 d. According to behavioral observation, the detection of levels of acetylcholinesterase (AchE), iron, and mRNA expression levels of blood-brain barrier (BBB) related tight junction proteins (ZO-1, Claudin7, Occludin, MMP2, MMP9, and MMP13) in brain tissues, it was found that SIL relieved neurobehavioral disorders caused by ABM-induced BBB destruction in carp. H&E staining showed SIL mitigated nerve injury and liver injury caused by ABM. Oil Red O staining and liver-related parameters showed that SIL alleviated hepatotoxicity and lipid metabolism disorder caused by ABM exposure. Furthermore, this work also explored the specific molecular mechanism of SIL in liver protection and neuroprotection. It was shown that SIL lowered ROS levels in liver and brain tissues via the GSK-3ß/TSC2/TOR pathway. Simultaneously, SIL inhibited NF-κB signaling pathway and played an anti-inflammatory role. In conclusion, we believed that SIL supplementation has a protective effect on the brain and liver by regulating oxidative stress and inflammation.

Impact of nitrite exposure on oxidative stress and antioxidative-related genes responses in the gills of Procambarus clarkii.

Nitrite is the major environmental pollutant in the freshwater aquaculture environment, which has a negative impact on aquatic species growth. Currently, we know that the main way nitrite enters crustaceans is through their gills. In this study, a total of 96 h acute nitrite stress (60 mg/L) experiments were conducted, and the impact of the serum biochemical parameters, gill oxidase activity and oxidative-related gene expression of red swamp crayfish were evaluated. After exposure to nitrite for 0, 6, 12, 24, 48, and 96 h, hemolymph and gills samples were taken at each time point. In the serum, acute nitrite stress significantly increased glutamic-oxaloacetic transaminase (GOT) and alanine aminotransferase (ALT) activities after 6 h of exposure, decreased total protein (TP) and albumin (ALB) levels after 24 h and 48 h of exposure, respectively. In the gills, the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were enhanced to the maximum level at 12 h, 24 h and 24 h, respectively. The contents of malondialdehyde (MDA) and lipid peroxide (LPO) were increased significantly after 12 h and 24 h exposure, respectively. In addition, the expression levels of antioxidative-related genes, including hsp70, fer and mt, were significantly upregulated in the gills after 6 h of exposure. The results indicated that acute nitrite stress changed the serum physiological status, induced oxidative stress and caused damage to gill cells in P. clarkii.

Kinetic Modeling of API Oxidation: (1) The AIBN/H2O/CH3OH Radical "Soup".

Stress testing of active pharmaceutical ingredients (API) is an important tool used to gauge chemical stability and identify potential degradation products. While different flavors of API stress testing systems have been used in experimental investigations for decades, the detailed kinetics of such systems as well as the chemical composition of prominent reactive species, specifically reactive oxygen species, are unknown. As a first step toward understanding and modeling API oxidation in stress testing, we investigated a typical radical "soup" solution an API is subject to during stress testing. Here we applied ab initio electronic structure calculations to automatically generate and refine a detailed chemical kinetics model, taking a fresh look at API oxidation. We generated a detailed kinetic model for a representative azobis(isobutyronitrile) (AIBN)/H2O/CH3OH stress-testing system with a varied cosolvent ratio (50%/50%-99.5%/0.5% vol water/methanol) for 5.0 mM AIBN and representative pH values of 4-10 at 40 °C that was stirred and open to the atmosphere. At acidic conditions, hydroxymethyl alkoxyl is the dominant alkoxyl radical, and at basic conditions, for most studied initial methanol concentrations, cyanoisopropyl alkoxyl becomes the dominant alkoxyl radical, albeit at an overall lower concentration. At acidic conditions, the levels of cyanoisopropyl peroxyl, hydroxymethyl peroxyl, and hydroperoxyl radicals are relatively high and comparable, while, at both neutral and basic pH conditions, superoxide becomes the prominent radical in the system. The present work reveals the prominent species in a common model API stress testing system at various cosolvent and pH conditions, sets the stage for an in-depth quantitative API kinetic study, and demonstrates the usage of novel software tools for automated chemical kinetic model generation and ab initio refinement.

Apolipoprotein-AI and AIBP synergetic anti-inflammation as vascular diseases therapy: the new perspective.

Vascular diseases (VDs) including pulmonary arterial hypertension (PAH), atherosclerosis (AS) and coronary arterial diseases (CADs) contribute to the higher morbidity and mortality worldwide. Apolipoprotein A-I (Apo A-I) binding protein (AIBP) and Apo-AI negatively correlate with VDs. However, the mechanism by which AIBP and apo-AI regulate VDs still remains unexplained. Here, we provide an overview of the role of AIBP and apo-AI regulation of vascular diseases molecular mechanisms such as vascular energy homeostasis imbalance, oxidative and endoplasmic reticulum stress and inflammation in VDs. In addition, the role of AIBP and apo-AI in endothelial cells (ECs), vascular smooth muscle (VSMCs) and immune cells activation in the pathogenesis of VDs are explained. The in-depth understanding of AIBP and apo-AI function in the vascular system may lead to the discovery of VDs therapy.

Reactive oxygen species scavenging and inflammation mitigation enabled by biomimetic prussian blue analogues boycott atherosclerosis.

BACKGROUND: As one typical cardiovascular disease, atherosclerosis severely endanger people' life and cause burden to people health and mentality. It has been extensively accepted that oxidative stress and inflammation closely correlate with the evolution of atherosclerotic plaques, and they directly participate in all stages of atherosclerosis. Regarding this, anti-oxidation or anti-inflammation drugs were developed to enable anti-oxidative therapy and anti-inflammation therapy against atherosclerosis. However, current drugs failed to meet clinical demands. METHODS: Nanomedicine and nanotechnology hold great potential in addressing the issue. In this report, we engineered a simvastatin (Sim)-loaded theranostic agent based on porous manganese-substituted prussian blue (PMPB) analogues. The biomimetic PMPB carrier could scavenge ROS and mitigate inflammation in vitro and in vivo. Especially after combining with Sim, the composite Sim@PMPB NC was expected to regulate the processes of atherosclerosis. As well, Mn2+ release from PMPB was expected to enhance MRI. RESULTS: The composite Sim@PMPB NC performed the best in regulating the hallmarks of atherosclerosis with above twofold decreases, typically such as oxidative stress, macrophage infiltration, plaque density, LDL internalization, fibrous cap thickness and foam cell birth, etc. Moreover, H2O2-induced Mn2+ release from PMPB NC in atherosclerotic inflammation could enhance MRI for visualizing plaques. Moreover, Sim@PMPB exhibited high biocompatibility according to references and experimental results. CONCLUSIONS: The biomimetic Sim@PMPB theranostic agent successfully stabilized atherosclerotic plaques and alleviated atherosclerosis, and also localized and magnified atherosclerosis, which enabled the monitoring of H2O2-associated atherosclerosis evolution after treatment. As well, Sim@PMPB was biocompatible, thus holding great potential in clinical translation for treating atherosclerosis.

Retracted: Knockdown of long noncoding RNA GAS5 attenuates H2 O2 -induced damage in retinal ganglion cells through upregulating miR-124: Potential role in traumatic brain injury.

BACKGROUND: Optic nerve injury is one of the most common and serious complications in traumatic brain injury (TBI). Alleviating degree of optic nerve injury is important to cure of TBI. This study explored the role of long noncoding RNA (lncRNA) GAS5 in mice retinal ganglion cells (RGCs) suffered to H2 O 2 injury. METHODS: Primary RGC (PRGCs) were treated with H2 O 2 to simulate an in vitro oxidation stress model. LncRNA GAS5 and miR-124 expressions were knocked down by cell transfection with short-hairpin RNA against GAS5 and miR-124 inhibitor, and the transfection efficiency was determined by qRT-PCR. Cell viability, apoptotic cell rate, and production of reactive oxygen species (ROS) was analyzed by CCK-8 assay, PI/FITC-Annexin V method, and DCFH-DA fluorometric assay. Cell apoptosis-associated proteins as well as activations of JAK/STAT3 signaling and JNK signaling were analyzed by Western blot. RESULTS: H2 O 2 treatment-induced cell injury was inhibited by lncRNA GAS5 silence. Specifically, knockdown of GAS5 improved viability of primary PRGCs, inhibited apoptosis, decreased ROS expression, increased antiapoptosis proteins' expressions, and decreased proapoptosis proteins' expressions. It was also found that miR-124 inhibitor treatment impaired the cell protective effect of GAS5 silence, indicating low level of GAS5 protected PRGCs via upregulating miR-124. GAS5 silence might exert cytoprotection effect via activating JAK/STAT3 signaling pathway and inhibiting activation of JNK signaling pathway. CONCLUSION: Knocking down lncRNA GAS5 alleviated H2 O 2 -induced injury in PRGCs via upregulation of miR-124, which might dependent on activation of JAK/STAT3 signaling pathway and inhibition of JNK signaling pathway.

Reproductive toxicity of acute Cd exposure in mouse: Resulting in oocyte defects and decreased female fertility.

Cadmium (Cd), a known metal contaminant, is widespreadly used in industry, thereby human health is severely affected through the way of occupational and environmental exposure. The adverse effects of the exposure to Cd on the female reproductive system, especially oocyte maturation and fertility have not been clearly defined. In this study, we found the arrested development of ovaries and uteri after Cd exposure and determined oocyte quality via assessing the key regulators during meiotic maturation and fertilization. We found that Cd exposure impeded the mouse oocyte meiotic progression by disrupting the normal spindle assembly, chromosome alignment and actin cap formation. Besides, exposure to Cd induced oxidative stress with the increased reactive oxygen species and apoptosis levels, leading to abnormal mitochondrial distribution, insufficient energy supply, and DNA damage, which ultimately led to oocyte quality deterioration. We also analyzed the effects of cadmium on epigenetic modifications, and the levels of 5mC, H3K9me3 and H3K9ac decreased after acute exposure to cadmium. Further experiments showed that the litter size in Cd-exposed female mice reduced, thereby indicating increased reproductive Cd toxicity. In conclusion, Cd exposure impairs oocyte maturation and fertilization ability induced by oxidative stress, early apoptosis and epigenetic modifications, which lead to the decrease of female fertility.

Copper nanoparticles induced oxidation stress, cell apoptosis and immune response in the liver of juvenile Takifugu fasciatus.

Copper nanoparticles (Cu NPs) are a new pollutant in aquaculture, representing a hazard to aquatic organisms. We investigated the effects of Cu NPs exposure on oxidative stress, apoptosis and immune response in an economically important model species, Takifugu fasciatus. The juvenile fish were exposed to control, 20 or 100 µg Cu NPs/L for 30 days. The growth of T. fasciatus was inhibited after Cu NPs exposure. Copper accumulation in liver increased with increasing Cu NPs dose. Oxidative stress indicators [malondialdehyde (MDA), total superoxide dismutase (T-SOD), catalase (CAT) and glutathione (GSH)], apoptosis index and activities of caspases (caspase-3, caspase-9) were all increased with the increase of Cu NPs concentration in liver. With an increase in Cu NPs dose, the activities of succinate dehydrogenase (SDH) and Na+-K+-ATPase as well as cytochrome c (Cyt-c) concentration in mitochondria decreased, accompanied by increased Cyt-c concentration in cytosol. Apoptosis-related gene expressions of p53, caspase-3, caspase-9 and Bax were increased with the increase of Cu NPs dose. However, the opposite result was found in Bcl2 expression. The physiological indicators of immune response [heat shock protein 70 (HSP70), heat shock protein 90 (HSP90), immunoglobulin M (IgM) and lysozyme (LZM)] as well as the mRNA levels of HSP70, HSP90, IgM and C-LZM were all increased after Cu NPs exposure. Our results will be helpful in understanding the mechanism of Cu NPs toxicity in T. fasciatus.

Plant protein diet suppressed immune function by inhibiting spiral valve intestinal mucosal barrier integrity, anti-oxidation, apoptosis, autophagy and proliferation responses in amur sturgeon (Acipenser schrenckii).

An 8-week growth trial was conducted to investigate the effects of replacing dietary fishmeal with a plant protein blend on the growth performance, mucosal barrier integrity and the related regulation mechanism in Amur Sturgeon (Acipenser schrenckii) with initial weight of 87.48 g. Three isonitrogenous and isoenergetic diets were prepared. A basal diet containing 540 g/kg fishmeal (P0), whereas the other two diets were formulated by replacing 50% and 100% of FM with plant protein blend (soybean protein concentrate and cottonseed protein concentrate), and named as P50 and P100, respectively. Although essential amino acids, fatty acids, and available phosphorus had been balanced according to the nutrient requirement of sturgeon, compared with the fish of P0 and P50, the full plant protein diet (P100) significantly reduced growth performance and survival, and accompanied with serious spiral valve intestinal (SVI) damage. The increased tissue necrosis and failed responses in anti-oxidation, programming apoptosis, autophagy and cell proliferation system were regulated by inhibiting ERK1 phosphorylation, which indicated that SVI hypoimmunity and functional degradation were the main reasons for the high mortality and low utilization ability of plant protein in Amur sturgeon.

Influence of total polar compounds on lipid metabolism, oxidative stress and cytotoxicity in HepG2 cells.

BACKGROUND: Recently, the harmful effects of frying oil on health have been gradually realized. However, as main components of frying oils, biochemical effects of total polar compounds (TPC) on a cellular level were underestimated. METHODS: The effects of total polar compounds (TPC) in the frying oil on the lipid metabolism, oxidative stress and cytotoxicity of HepG2 cells were investigated through a series of biochemical methods, such as oil red staining, real-time polymerase chain reaction (RT-PCR), cell apoptosis and cell arrest. RESULTS: Herein, we found that the survival rate of HepG2 cells treated with TPC decreased in a time and dose dependent manner, and thereby presented significant lipid deposition over the concentration of 0.5 mg/mL. TPC were also found to suppress the expression levels of PPARα, CPT1 and ACOX, elevate the expression level of MTP and cause the disorder of lipid metabolism. TPC ranged from 0 to 2 mg/mL could significantly elevate the amounts of reactive oxygen species (ROS) in HepG2 cells, and simultaneously increase the malondialdehyde (MDA) content from 21.21 ± 2.62 to 65.71 ± 4.20 µmol/mg of protein (p < 0.05) at 24 h. On the contrary, antioxidant enzymes superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) respectively decreased by 0.52-, 0.56- and 0.28-fold, when HepG2 cells were exposed to 2 mg/mL TPC for 24 h. In addition, TPC could at least partially induce the apoptosis of HepG2 cells, and the transition from G0/G1 to G2 phase in HepG2 cells was impeded. CONCLUSIONS: TPC could progressively cause lipid deposition, oxidative stress and cytotoxicity, providing the theoretical support for the detrimental health effects of TPC.

Mono-2-ethylhexyl phthalate (MEHP) promoted lipid accumulation via JAK2/STAT5 and aggravated oxidative stress in BRL-3A cells.

Mono-2-ethylhexyl phthalate (MEHP), as the major metabolite of Di-(2-ethylhexyl) phthalate (DEHP), can induce lipid accumulation in hepatocytes and further leads to non-alcoholic fatty liver disease (NAFLD), while the underlying mechanism is unclear. We aim to clarify the effects of JAK2/STAT5 pathway on lipid accumulation induced by MEHP and the role of oxidation stress in NAFLD. BRL-3A hepatocytes were exposed to MEHP (0, 10, 50, 100 and 200 µM) for 24 h and 48 h. Then the lipid droplets in cells were observed by Oil-Red-O staining and quantified by isopropyl alcohol. The levels of TG, SOD, TBARS, AST and ALT were all detected by commercial kits. RT-PCR was used to detect mRNA expression, and western blotting was used to detect the expression of proteins encoded by JAK2/STAT5 pathway genes and lipid metabolism-related genes. As a result, MEHP promoted the lipid synthesis and accumulation in BRL-3A cells. MEHP down-regulated the expression and inhibited the activation of JAK2/STAT5. Moreover, the lipid metabolism-related kinases levels were elevated after MEHP exposure. In addition, the SOD levels were gradually decreased and the TBARS levels were increased in MEHP-treated groups. The lipid metabolism-related proteins levels were correlated with the oxidation stress levels. Furthermore, the ALT and AST levels were elevated after MEHP exposure. Therefore, we concluded that MEHP led to lipid accumulation through inhibiting JAK2/STAT5 pathway, resulted in damaging liver parenchyma and NAFLD by aggravating oxidation stress.

Sub-chronic toxicopathological study of lantadenes of Lantana camara weed in Guinea pigs.

BACKGROUND: In the field conditions, animals regularly consume small quantities of lantana leaves either while grazing or due to mixing with regular fodder. The hypothesis of this study was that consumption of lantana toxins over a long period of time leads to progression of sub-clinical disease. Toxicopathological effects of sub-chronic (90 days) administration of lantadenes of L. camara were investigated in guinea pigs. For this, a total of 40 animals were divided into 5 groups whereby groups I, II, III and IV were orally administered lantadenes, daily at the dose of 24, 18, 12, and 6 mg/kg bw, respectively while group V was control. The animals were evaluated by weekly body weight changes, haematology, serum liver and kidney markers, tissue oxidative markers and histopathology. RESULTS: The results of significant decrease in weekly body weights, haematology, liver and kidney marker enzymes (alanine aminotransaminase, aspartate aminotransaminase, acid phosphatase and creatinine), oxidation stress markers (lipid peroxidation, reduced glutathione, superoxide dismutase and catalase) in liver and kidneys, histopathology, and confirmation of fibrous collagenous tissue proliferation by Masson's Trichome stain showed that lantadenes led to a dose-dependent toxicity in decreasing order with the highest dose (24 mg/kg bw) producing maximum lesions and the lowest dose (6 mg/kg bw) producing minimum alterations. CONCLUSIONS: The study revealed that lantadenes which are considered to be classical hepatotoxicants in acute toxicity produced pronounced nephrotoxicity during sub-chronic exposure. Further studies are needed to quantify the levels of lantadenes in blood or serum of animals exposed to lantana in field conditions which would help to assess the extent of damage to the vital organs.

Ginsenoside Rb1 Attenuates Isoflurane/surgery-induced Cognitive Dysfunction via Inhibiting Neuroinflammation and Oxidative Stress.

OBJECTIVE: Anesthetic isoflurane plus surgery has been reported to induce cognitive impairment. The underlying mechanism and targeted intervention remain largely to be determined. Ginsenoside Rb1 was reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rb1 can attenuate isoflurane/surgery-induced cognitive dysfunction via inhibiting neuroinflammation and oxidative stress. METHODS: Five-months-old C57BL/6J female mice were treated with 1.4% isoflurane plus abdominal surgery for two hours. Sixty mg/kg ginsenoside Rb1 were given intraperitoneally from 7 days before surgery. Cognition of the mice were assessed by Barnes Maze. Levels of postsynaptic density-95 and synaptophysin in mice hippocampus were measured by Western blot. Levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in mice hippocampus were measured by ELISA. RESULTS: Here we show for the first time that the ginsenoside Rb1 treatment attenuated the isoflurane/surgery-induced cognitive impairment. Moreover, ginsenoside Rb1 attenuated the isoflurane/surgery-induced synapse dysfunction. Finally, ginsenoside Rb1 mitigated the isoflurane/surgery-induced elevation levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in the mice hippocampus. CONCLUSION: These results suggest that ginsenoside Rb1 may attenuate the isoflurane/surgery-induced cognitive impairment by inhibiting neuroinflammation and oxidative stress pending future studies.

Chemical fractionation and mobility of traffic-related elements in road environments.

Due to considerable progress in exhaust control emission technology and extensive regulatory work regarding this issue, non-exhaust sources of air pollution have become a growing concern. This research involved studying three types of road environment samples such as road dust, sludge from storm drains and roadside soil collected from heavily congested and polluted cities in Poland (Krakow, Warszawa, Opole and Wroclaw). Particles below 20 µm were examined since it was previously estimated that this fine fraction of road dust is polluted mostly by metals derived from non-exhaust sources of pollution such as brake linings wear. Chemical analysis of all samples was combined with a fractionation study using BCR protocol. It was concluded that the finest fractions of road environment samples were significantly contaminated with all of the investigated metals, in particular with Zn, Cu, both well-known key tracers of brake and tire wear. In Warszawa, the pollution index for Zn was on average 15-18 times the background value, in Krakow 12 times, in Wroclaw 8-12 times and in Opole 6-9 times the background value. The pollution index for Cu was on average 6-14 times the background in Warszawa, 7-8 times in Krakow, 4-6 times in Wroclaw and in Opole 5 times the background value. Fractionation study revealed that mobility of examined metals decreases in that order: Zn (43-62%) > Cd (25-42%) > Ni (6-16%) > Cu (3-14%) > Pb (1-8%). It should, however, be noted that metals even when not mobile in the environment can become a serious health concern when ingested or inhaled.

[The evaluation of oxidation stress in umbilical blood and lysate of endothelial cells of vessels of umbilical cord of newborns.]

The sampling of newborns (n=28) was examined. Out of them, 18 premature children formed main group (gestation age from 28 to35 weeks, body mass 2067,3±76,7g) and 10 mature children formed comparison group (gestation age from 38 to 41 weeks, body mass 3380,2±57,2g) born from mothers with physiologically occurring pregnancy without extra-genital pathology. In all children, the detection of endothelial cells isolated from umbilical cord vein in mixed umbilical blood and lysate was applied and indices of free radical oxidation of lipids, characterizing oxidizing stress as well and anti-oxidation activity using chemiluminescence technique. The study results demonstrated in premature newborns increasing in umbilical blood of indices of fast flash chemiluminescence (Imax), light sun value (S) and tangent of kinetic curve slope (tga) and also increasing of parameters Imax and tga in lysate of endothelial cells of umbilical cord. Al these occurrences testify in these children development oxidation stress being accompanied by compensation increasing of antioxidant activity.

Effect of copper nanoparticles and copper sulphate on oxidation stress, cell apoptosis and immune responses in the intestines of juvenile Epinephelus coioides.

Copper nanoparticles (Cu-NPs) are widely used in various industrial and commercial applications, but little is known about their potential hazard in the intestines of marine teleosts. In this study we investigated the effects of Cu-NPs and soluble Cu in the intestines of juvenile Epinephelus coioides. The fish were exposed in triplicate to control, 20 or 100 µg Cu L(-1) as either copper sulphate (CuSO4) or Cu-NPs for 25 days. With an increase in Cu-NPs or CuSO4 dose, the concentration of malonaldehyde in the intestines significantly increased, whereas the activities of total superoxide dismutase and catalase as well as glutathione concentration decreased compared to the control. Statistical analysis of an apoptosis index of intestinal cells showed that general dose-dependent apoptosis was induced by Cu-NPs or CuSO4, with Cu-NPs inducing the significantly higher apoptosis index than CuSOv. Caspase-3 and caspase-9 activities were increased with an increase in Cu-NPs or CuSO4 dose, more so in the Cu-NPs than CuSO4 treatment. With an increase in Cu-NPs or CuSOv dose, succinate dehydrogenase and Na(+)-K(+)-ATPase activity and cytochrome c concentration in mitochondria decreased, accompanied by increased cytochrome c concentration in the cytosol. Concentration of heat shock proteins 70 and 90 in the intestines and expression of corresponding genes were enhanced with an increase in the Cu-NPs or CuSOv dose, but the concentrations and expressions of immunoglobulin M and lysozyme decreased (more in the Cu-NPs than CuSO4 treatment) compared to the control. Expression of interleukin-1beta and tumor necrosis factor-alpha showed a dose-dependent increase with the increased Cu-NPs or CuSO4 dose, with the highest expression found in the Cu-NPs treatment. In conclusion, Cu-NPs had similar toxic effects as CuSOv in the intestines of juvenile E. coioides, but toxicity of Cu-NPs was more severe than that of CuSO4.

Influence of ovarian stimulation for IVF/ICSI on the antioxidant defence system and relationship to outcome.

Ovarian stimulation is used with IVF/intracytoplasmic sperm injection (ICSI) cycles to obtain multiple oocytes and improve pregnancy rates; however, it also induces perturbation in the oxidant-antioxidant balance leading to oxidation stress. The present study monitored the plasma antioxidant status in women undergoing a long agonist protocol of ovarian stimulation at three different time points: at baseline (T0), after pituitary suppression (T1) and on the day of oocyte retrieval (T2). The antioxidant composition of follicular fluid samples collected on T2 was also evaluated. Significant decreases (P < 0.05) of plasma vitamin C, vitamin E and carotenoids were found between T1 and T2 but not between T0 and T1. At T2, high plasma vitamin E was associated with high numbers of total and mature oocytes retrieved per patient, which, in turn, were favourable for achieving pregnancy. Accordingly, women who became pregnant presented higher vitamin E concentrations both in plasma and FF than those who did not. In conclusion, this study confirmed the occurrence of significant modifications of the plasma antioxidant profile during ovarian stimulation with gonadotrophins; at the same time, it was found that both systemic and follicular antioxidant status may be related to IVF/ICSI outcome.

Selenomethionine protects the liver from dietary deoxynivalenol exposure via Nrf2/PPARγ-GPX4-ferroptosis pathway in mice.

Deoxynivalenol (DON) is a significant Fusarium toxin that has gained global attention due to its high frequency of contamination in food and feed. It was reported to have hepatotoxicity, immunotoxicity, and reproduction toxicity in organs. On the other hand, Selenomethionine (SeMet) was proven to have anti-oxidation, tissue repairing, immunity improvement, and antifungal mycotoxin infection functions. However, the molecular mechanism by which SeMet alleviates DON damage is not yet clear. C57BL/6 mice were randomly divided into three groups, Se-A and Se-A+DON were fed with a diet containing 0.2 mg/kg Se whereas Se-S+DON were fed with a diet of 1.0 mg/kg Se. After feeding for four weeks, the mice were gavaged for 21 days with DON (2.0 mg/kg BW) or ultrapure water once per day. In the present study, we showed that SeMet significantly decreased the lipid peroxidation product malondialdehyde, and increased activities of antioxidant enzymes superoxide dismutase and total antioxidant capacity after DON exposure. In addition, our investigation revealed that SeMet regulated pathways related to lipid synthesis and metabolisms, and effectively mitigated DON-induced liver damage. Moreover, we have discovered that SeMet downregulation of N-acylethanolamine and HexCer accumulation induced hepatic lipotoxicity. Further study showed that SeMet supplementation increased protein levels of glutathione peroxidase 4 (GPX4), peroxisome proliferator-activated receptor γ (PPARγ), nuclear erythroid 2-related factor 2 (Nrf2), and upregulated target proteins, indicating suppression of oxidative stress in the liver. Meanwhile, we found that SeMet significantly reduced the DON-induced protein abundances of Bcl2, Beclin1, LC3B and proteins related to ferroptosis (Lpcat3, and Slc3a2), and downregulation of Slc7a11. In conclusion, SeMet protected the liver from damage by enhancing the Nrf2/PPARγ-GPX4-ferroptosis pathway, inhibiting lipid accumulation and hepatic lipotoxicity. The findings of this study indicated that SeMet has a positive impact on liver health by improving antioxidant capacity and relieving lipotoxicity in toxin pollution.

Effects of tire wear particle on growth, extracellular polymeric substance production and oxidation stress of algae Chlorella vulgaris: Performance and mechanism.

Tire wear particles (TWP) represent a distinctive form of microplastics (MPs) that are widely distributed in aquatic ecosystems. However, the toxicity of various types of TWP on phytoplankton remain to be further explored. Thus, three different TWPs originating from replaced bicycle, car, and electro-mobile tire (marked as BTWP, CTWP, and ETWP) were selected and their long-term biological influences on Chlorella vulgaris were investigated. Results demonstrated TWPs showed a concentration-dependent growth promotion of Chlorella vulgaris, with a maximum promotion rate reached to 40.51 % (10 mg/L, 10 d), 23.5 % (80 mg/L, 12 d), and 28.7 % (20 mg/L, 12 d) in the presence of BTWP, CTWP and ETWP, respectively. Meanwhile, TWPs could stimulate the secretion of EPS and induce oxidative stress. EPS analysis revealed the increase of polysaccharides could protect the cell from the direct contact with TWP particles. Moreover, the increased concentration of EPS also helps to induce the settlement of TWP and reduce the leachate release. The release of TWP into the environment could act as an accelerator for the growth of Chlorella vulgaris, which might further change the normal physicochemical behaviors of algae colony in aquatic system. Our findings provide new insights into the toxicity mechanism of TWPs on freshwater algae and valuable data on environmental risk assessment of TWPs.