The aim of the present study was to investigate the role of ferroptosis in acute lung injury (ALI) mouse model induced by oleic acid (OA). ALI was induced in the mice via the lateral tail vein injection of pure OA. The histopathological score of lung, lung wet-dry weight ratio and the protein content of bronchoalveolar lavage fluid (BALF) were used as the evaluation indexes of ALI. Iron concentration, glutathione (GSH) and malondialdehyde (MDA) contents in the lung tissues were measured using corresponding assay kits. The ultrastructure of pulmonary cells was observed by transmission electron microscope (TEM), and the expression level of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA was detected by quantitative polymerase chain reaction (q-PCR). Protein expression levels of glutathione peroxidase 4 (GPX4), ferritin and transferrin receptor 1 (TfR1) in lung tissues were determined by Western blot. The results showed that histopathological scores of lung tissues, lung wet-dry weight ratio and protein in BALF in the OA group were higher than those of the control group. In the OA group, the mitochondria of pulmonary cells were shrunken, and the mitochondrial membrane was ruptured. The expression level of PTGS2 mRNA in the OA group was seven folds over that in the control group. Iron overload, GSH depletion and accumulation of MDA were observed in the OA group. Compared with the control group, the protein expression levels of GPX4 and ferritin in lung tissue were down-regulated in the OA group. These results suggest that ferroptosis plays a potential role in the pathogenesis of ALI in our mouse model, which may provide new insights for development of new drugs for ALI.
Acute Lung Injury ; chemically induced ; pathology ; Animals ; Apoptosis ; Bronchoalveolar Lavage Fluid ; chemistry ; Cyclooxygenase 2 ; metabolism ; Ferritins ; metabolism ; Glutathione ; analysis ; Glutathione Peroxidase ; metabolism ; Iron ; analysis ; Iron Overload ; physiopathology ; Lung ; cytology ; pathology ; Malondialdehyde ; analysis ; Mice ; Microscopy, Electron, Transmission ; Mitochondrial Membranes ; ultrastructure ; Oleic Acid

This study investigated the correlation between oxidative stress status and key canine sperm parameters and the effect of addition of a superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) combination in egg yolk tris-citrate glucose (EYT-G) extender on semen during 10 days of storage at 4℃. Ten Boxer dogs were divided into two groups, fertile (F) and hypofertile (H), depending on pregnancy and live birth rate status in the previous year. Semen evaluation was performed on the day of collection (D0) and after 5 (D5) and 10 (D10) days of cooled storage. Sperm motility, kinetic parameters, and DNA integrity were assessed. A correlation between oxidative status and key semen parameters in both F and H groups was observed. Total and progressive motilities were significantly higher in the treated (SOD, CAT, and GPx addition) versus control groups at D10 in both F and H groups, and at D5 in the H group. DNA integrity was significantly higher in both treated groups (H and F) at D5 and D10. In conclusion, the addition of SOD, CAT, and GPx in the extender allows preservation of semen quality for up to 10 days of storage at 4℃ in both fertile and hypofertile dogs.
Animals ; Antioxidants ; Catalase ; Cats ; DNA ; Dogs ; Egg Yolk ; Fertility ; Glucose ; Glutathione Peroxidase ; Glutathione ; Live Birth ; Oxidative Stress ; Pregnancy ; Semen Analysis ; Semen Preservation ; Semen ; Sperm Motility ; Spermatozoa ; Superoxide Dismutase ; Superoxides

OBJECTIVES: To investigate the interventional effects of 16-week aerobic exercises on the elderly's arteriosclerosis and its mechanism. METHODS: Twenty-seven elderly people with the average age of 62. 70 ±3. 26 joined a 16-week square dance/taijiquan exercise program that conducted 60 minutes each time, six times per week. Arterial stiffness and its related indexes such as systolic pressure(SBP), diastolic pressure(DBP), left brachial-ankle pulse wave velocity (L-baPWV), right brachial-ankle pulse wave velocity(R-baPWV), left ankle brachial index (L-ABI), right ankle brachial index(R-ABI), serum triglyceride(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-c), low density lipoprotein cholesterol(LDL-c), superoxide dismutase(SOD), malondialdehyde(MDA) and glutathione peroxidase (GSH-Px) were detected at 3 time points including before exercise program, by the end of exercise for 8 weeks and 16 weeks. RESULTS: ① Compared with pre-exercise, the R-baPWV and R-ABI of the elderly people were decreased at the end of the 8 week, and the L-baPWV, RbaPWV, R-ABI and L-ABI were decreased significantly at the end of the 16 week. ②Compared with pre-exercise, SBP and DBP were declined markedly (<0.01, <0.05) at the end of the 8 week, SBP, DBP and pulse pressure were decreased significantly (<0.01, <0.05) at the end of the 16 week. ③Compared with pre-exercise, TC and LDL-c were declined markedly (<0.01) at the end of the 8 and the 16 week, and there was no difference of the level of TG and LDL-c between pre-exercise and post-exercise. ④There was no evident difference of serum level of SOD, GSH-Px, MDA between pre-exercise and post-exercise at the end of the 8 week. Compared with pre-exercise, the level of serum SOD, GSH-Px was increased evidently while the content of serum MDA was decreased significantly (<0.01). CONCLUSIONS Sixteen-week aerobic exercises could reduce baPWV and ABI levels, regulate blood pressure, blood lipids and lipid peroxides levels of the elderly evidently, thus improve the controlling quality of atherosclerosis.
Aged ; Ankle ; Ankle Brachial Index ; Arteriosclerosis ; therapy ; Blood Pressure ; Cholesterol ; blood ; Exercise ; Glutathione Peroxidase ; blood ; Humans ; Malondialdehyde ; blood ; Middle Aged ; Pulse Wave Analysis ; Superoxide Dismutase ; blood ; Triglycerides ; blood

Objective: To investigate the influence of deep slow-wave sleep deprivation on the oxidative stress of testicular tissue in rats. METHODS: Thirty-six 5-week-old male Wistar rats were equally randomized into deep slow-wave sleep deprivation group (SD1), deep slow-wave sleep and duration sleep deprivation group ( SD2), and a cage control group (CC). The rat model of deep slow-wave sleep deprivation was established using the flowerpot technique. The rats in the SD1 group were interfered every 24 minutes and deprived of 12 hours of sleep at night, those in the SD2 group deprived of 8 minutes of sleep at an interval of 24 minutes and 12 hours of sleep at night, and those in the CC group exposed to 12 hours of daylight and 12 hours of darkness. After 28 days, all the rats were executed for measurement of the testis volume and protein content, determination of the methane dicarboxylic aldehyde (MDA) level and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and observation of the pathological changes in the testicular tissue under the microscope. RESULTS: Compared with the CC group, the rats in the SD1 and SD2 groups showed significantly reduced body weight (［268.5 ± 1.6］ vs ［248.1 ± 25.1］and［232.9 ± 10.1］g, P<0.05) and increased relative testis mass (［50.0 ± 1.3］ vs ［57.9 ± 6.1］ and ［54.9 ± 3.5］ ×10⁻², P<0.05). Statistically significant differences were found between the CC and SD2 groups in the contents of protein (［6.3 ± 1.4］ vs ［4.5 ± 0.9］ gpro/L, P<0.05) and MDA (［1.1 ± 0.1］ vs ［1.3 ± 0.3］ nmol/mgpro, P<0.05) and the activities of SOD (［104.3 ± 33.1］ vs ［135.2 ± 26.9］ U/mgpro, P<0.05) and GSH-Px (［15.6 ± 4.0］ vs ［21.7 ± 4.3］ U/mgpro, P<0.05), but not between the CC and SD1 groups (P>0.05). The lumens in the testis were narrowed, with obvious hyperplasia, hyperemia and edema in the peripheral interstitial tissue, but no significant pathologic changes were observed in the testis tissue of the SD1 group. CONCLUSIONS Long-term deprivation of deep slow-wave sleep impairs the structure of the testis tissue and induces oxidative stress response in rats.
Animals ; Body Weight ; Glutathione Peroxidase ; analysis ; Male ; Malondialdehyde ; Oxidative Stress ; Random Allocation ; Rats ; Rats, Wistar ; Sleep Deprivation ; metabolism ; Sleep Stages ; Superoxide Dismutase ; analysis ; Testis ; metabolism ; pathology ; Time Factors ; Weight Loss

To investigate the effects of cigarette smoking in different manners on acute lung injury in rats.The commercially available cigarettes with tar of 1,5, 11 mg were smoked in Canada depth smoking (health canada method, HCM) manner, and those with tar of 11 mg were also smoked in international standard (ISO) smoking manner. Rats were fixed and exposed to mainstream in a manner of nose-mouth exposure. After 28 days, the bronchoalveolar lavage fluids from left lung were collected for counting and classification of inflammatory cells and determination of pro-inflammatory cytokines IL-1β and TNF-α. The right lungs were subjected to histological examination and determination of myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and glutathione, reactive oxygen species (ROS) and malondialdehyde (MDA) levels.In both HCM and ISO manners, the degree of lung injury was closely related to the tar content of cigarettes, and significant decrease in the body weight of rats was observed after smoking for one week. In a HCM manner, smoking with cigarette of 11 mg tar resulted in robust infiltration of macrophages, lymphocytes and neutrophils into lungs, significant increase in IL-1β and TNF-α levels and MPO activities, and significant decrease in GSH levels and SOD activities and increase in ROS and MDA levels (all<0.05). Smoking with cigarette of 5 mg tar led to moderate increase in IL-1β and TNF-α levels, and MPO activities (all<0.05), and moderate decrease in GSH levels and SOD activities and increase of ROS and MDA levels (all<0.05). However, smoking with cigarette of 1 mg tar affected neither inflammatory cell infiltration nor IL-1β and TNF-α levels.Cigarette smoking in nose-mouth exposure manner can induce acute lung injury in rats; and the degree of lung injury is closely related to the content of tar and other hazards in cigarettes.
Acute Lung Injury ; etiology ; pathology ; physiopathology ; Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; cytology ; Chemotaxis, Leukocyte ; drug effects ; Glutathione ; analysis ; drug effects ; Interleukin-1beta ; analysis ; drug effects ; Lung ; chemistry ; pathology ; Lymphocytes ; drug effects ; pathology ; Macrophages ; drug effects ; pathology ; Male ; Malondialdehyde ; analysis ; Neutrophil Infiltration ; drug effects ; Neutrophils ; drug effects ; pathology ; Peroxidase ; analysis ; drug effects ; Rats ; Reactive Oxygen Species ; analysis ; Smoking ; adverse effects ; Superoxide Dismutase ; analysis ; drug effects ; Tobacco Products ; adverse effects ; classification ; Tumor Necrosis Factor-alpha ; analysis ; drug effects ; Weight Loss ; drug effects

This study was undertaken to investigate the antioxidant/oxidant status in recurrent miscarriage patients. Antioxidants including glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), reduced glutathione (GSH) and selenium (Se), as well as the oxidants hydrogen peroxide (H2O2), oxidised glutathione (GSSG) and lipid peroxidation were assayed in plasma, whole blood and placental tissue of non-pregnant women (NP), healthy pregnant women (HP), and recurrent miscarriage (RM) patients. Results indicated that all antioxidant activities and levels in plasma and whole blood of HP women were consistently moderately lower, and much more significantly lower in RM patients when both were compared to those seen in NP women (P<0.05 and P<0.001, respectively). Furthermore, whereas plasma antioxidant activities and levels were significantly lower in RM patients, those of whole blood and placental tissue were much more significantly lower when compared with HP women (P<0.001). Concurrent with these findings there were consistent increases of equal statistical significance and magnitude in the levels of all investigated oxidants assayed in all samples when compared in between subjects of the study as indicated above. Data thus illustrated a distinct shift in favor of oxidative reactions and reactive oxygen species (ROS) generation, and very significant decreases in the GSH/GSSG ratios in whole blood and placental tissue of RM patients when compared to HP and NP women (P<0.001). The above noted oxidative stress could have been a major causative factor of recurrent miscarriage.
Abortion, Habitual/*blood/*epidemiology ; Adult ; Antioxidants/analysis ; Biomarkers/*blood ; Catalase/blood ; Female ; Glutathione/blood ; Glutathione Peroxidase/blood ; Glutathione Reductase/blood ; Humans ; Hydrogen Peroxide/analysis ; Lipid Peroxidation ; *Oxidative Stress ; Placenta/metabolism ; Pregnancy ; Reactive Oxygen Species/metabolism ; Saudi Arabia/epidemiology ; Selenium/blood

OBJECTIVETo study the correlation between arachidonic acid (AA) and acute red blood cells damage in rats, and to build a model with hidden blood loss in vivo, and to explore the pathological mechenism of hidden blood loss.

METHODSA total of 50 male adult Sprague-Dawley rats weighing (200 ± 20) g were randomly divided into five groups (n = 10): control group and four experimental groups. The rats in the experimental groups were given 0.5 ml different concentrations of AA dilu- ents, 5, 10, 20, 40 mmol/L respectively. The blood samples were collected from orbital venous at the beginning and 24, 48, 72 hours after administration. Then the changes of hemoglobin (Hb) ,red blood cell count (RBC), glutathione peroxidase (GSH- PX) activity, total superoxide dismutase (T-SOD) activity and hydrogen peroxide (H202) in the blood samples were tested.

RESULTSSignificant hidden blood loss occurred when the concentration was 10 mmol/L in the experimental group, with the RBC and Hb sharply reduced in blood samples. The Hb and RBC were reduced in all the experimental groups and control group at 24 hours after administration, while in the experimental groups they changed more obviously. The GSH-PX activity, T-SOD activity and H₂O₂were also significantly reduced in all groups, and the changes showed significant differences. The Hb and RBC were relatively stable in the control group and the experimental groups at 48 hours after administration; while GSH-PX activity, T-SOD activity and H₂O₂were all significantly decreased, and the changes in the experimental groups were more notable.

CONCLUSIONElevated levels of AA in the blood causes oxidative stress in the red blood cells, leading to the damage of red blood cells and hemoglobin, which is responsible for hidden blood loss.

Animals ; Arachidonic Acid ; toxicity ; Erythrocytes ; drug effects ; metabolism ; Glutathione Peroxidase ; blood ; Hemoglobins ; analysis ; Male ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood

OBJECTIVETo investigate the effects of different dietary fat and oils (differing in their degree of saturation and unsaturation) on lipid peroxidation in liver and blood of rats.

METHODSThe study was conducted on 50 albino rats that were randomly divided into 5 groups of 10 animals. The groups were fed on dietary butter (Group I), margarine (Group II), olive oil (Group III), sunflower oil (Group IV) and corn oil (Group V) for 7 weeks. After 12 h of diet removal, livers were excised and blood was collected to measure malondialdehyde (MDA) levels in the supernatant of liver homogenate and in blood. Blood superoxide dismutase activity (SOD), glutathione peroxidase activity (GPx), serum vitamin E and total antioxidant capacity (TAC) levels were also measured to determine the effects of fats and oils on lipid peroxidation.

RESULTSThe results indicated that no significant differences were observed in SOD activity, vitamin E and TAC levels between the five groups. However, there was significant decrease of GPx activity in groups IV and V when compared with other groups. The results indicated that feeding corn oil caused significant increases in liver and blood MDA levels as compared with other oils and fats. There were positive correlations between SOD and GPx, vitamin E and TAC as well as between GPx and TAC (r: 0.743; P<0.001) and between blood MDA and liver MDA (r: 0.897; P<0.001). The results showed also negative correlations between blood MDA on one hand and SOD, GPx, vitamin E and TAC on the other hand.

CONCLUSIONSThe results demonstrated that feeding oils rich in polyunsaturated fatty acids (PUFA) increases lipid peroxidation significantly and may raise the susceptibility of tissues to free radical oxidative damage.

Analysis of Variance ; Animals ; Diet ; Dietary Fats ; pharmacology ; Dietary Fats, Unsaturated ; pharmacology ; Female ; Glutathione Peroxidase ; blood ; Lipid Peroxidation ; drug effects ; Male ; Malondialdehyde ; blood ; Plant Oils ; pharmacology ; Rats ; Superoxide Dismutase ; blood

Previous evidence supports the important role that oxidative stress (OxS) plays in metabolic syndrome (MetS)-related manifestations. We determined the relationship between the number of MetS components and the degree of OxS in MetS patients. In this comparative cross-sectional study from the LIPGENE cohort, a total of 91 MetS patients (43 men and 48 women; aged between 45 and 68 years) were divided into four groups based on the number of MetS components: subjects with 2, 3, 4 and 5 MetS components (n=20, 31, 28 and 12, respectively). We measured ischemic reactive hyperemia (IRH), plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), total nitrite, lipid peroxidation products (LPO), hydrogen peroxide (H2O2), superoxide dismutase (SOD) and glutathione peroxidase (GPx) plasma activities. sVCAM-1, H2O2 and LPO levels were lower in subjects with 2 or 3 MetS components than subjects with 4 or 5 MetS components. IRH and total nitrite levels were higher in subjects with 2 or 3 MetS components than subjects with 4 or 5 MetS components. SOD and GPx activities were lower in subjects with 2 MetS components than subjects with 4 or 5 MetS components. Waist circumference, weight, age, homeostatic model assessment-beta, triglycerides (TGs), high-density lipoprotein and sVCAM-1 levels were significantly correlated with SOD activity. MetS subjects with more MetS components may have a higher OxS level. Furthermore, association between SOD activity and MetS components may indicate that this variable could be the most relevant OxS biomarker in patients suffering from MetS and could be used as a predictive tool to determine the degree of the underlying OxS in MetS.
Aged ; Anthropometry ; Antioxidants/metabolism ; Biological Markers/metabolism ; Blood Pressure ; Endothelium, Vascular/pathology/physiopathology ; Female ; Glutathione Peroxidase/blood ; Humans ; Hydrogen Peroxide/metabolism ; Hyperemia/blood/physiopathology ; Male ; Metabolic Syndrome X/blood/enzymology/*pathology/physiopathology ; Middle Aged ; Nitrites/blood ; *Oxidative Stress ; Regression Analysis ; Superoxide Dismutase/blood ; Vascular Cell Adhesion Molecule-1/metabolism

OBJECTIVETo determine whether testosterone modulates markers of cardiomyocytes aging via its classic androgen receptor (AR)-dependent pathway or conversion to estradiol.

METHODSMale littermates and testicular feminized (Tfm) mice were randomly separated into 4 experimental groups littermate controls (n=8), Tfm mice (n=7), testosterone-treated Tfm mice (n=8), and Tfm mice treated with testosterone in combination with the aromatase inhibitor anastrazole (n=7). Cardiomyocytes were isolated from mouse left ventricles, the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the amount of malondialdehyde (MDA) were measured using colorimetry method, and expression of p16(INK4α) and retinoblastoma (Rb) proteins were detected by Western blotting.

RESULTSThe SOD and GSH-Px enzyme activities of cardiomyocytes were decreased, and the MDA levels and the expression of p16(INK4α) and Rb proteins were increased in Tfm mice compared with control mice. An increase was observed in the activities of SOD and GSH-Px enzyme as well as a decrease in MDA levels and the expression of p16(INK4α) and Rb proteins in the testosterone-treated Tfm mice. After co-treatment with anastrazole in Tfm mice, these improvement were partly inhibited.

CONCLUSIONPhysiological testosterone replacement can delay cardiomyocyte aging in Tfm mice, an effect that is independent of the AR pathway and in part conversion to estradiol.

Androgen-Insensitivity Syndrome ; metabolism ; Animals ; Cellular Senescence ; Cyclin-Dependent Kinase Inhibitor p16 ; analysis ; Female ; Glutathione Peroxidase ; metabolism ; Male ; Mice ; Myocytes, Cardiac ; physiology ; Receptors, Androgen ; physiology ; Superoxide Dismutase ; metabolism ; Testosterone ; physiology