Oxidative Stress In Male Mice Research Articles

Mechanisms of damage to sperm structure in mice on the zinc-deficient diet

BackgroundZinc (Zn)is an essential trace element for spermatogenesis and its deficiency causes abnormal spermatogenesis. ObjectiveThe present study was conducted to examine the mechanisms by which Zn-deficient diet impairs sperm morphology and its reversibility. Methods30 SPF grade male Kunming (KM) mice were randomly divided into three groups, 10 mice per group. Zn-normal diet group (ZN group) was given Zn-normal diet（Zn content= 30 mg/kg）for 8 weeks. Zn-deficienct diet group (ZD group) was given Zn-deficienct diet（Zn content< 1 mg/kg）for 8 weeks. Zn-deficient and Zn-normal diet group（ZDN group）was given 4 weeks Zn-deficienct diet followed by 4 weeks Zn-normal diet. After 8 weeks, the overnight fasted mice were sacrificed, and blood and organs were collected for further analysis. ResultsThe experimental results showed that Zn-deficienct diet leads to increased abnormal morphology sperm and testicular oxidative stress.The rate of abnormal morphology sperm, chromomycin A3(CMA3), DNA fragmentation index (DFI), malondialdehyde (MDA) were significantly increased, and a-kinase anchor protein 4(AKAP4), dynein axonemal heavy chain 1(DNAH1), sperm associated antigen 6(SPAG6), cilia and flagella associated protein 44(CFAP44), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), nuclear factor erythroid 2-related factor (NRF2), NAD(P)H:quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO1) were significantly decreased in the ZD group mice. While the changes in above indicators caused by Zn-deficient diet were significantly alleviated in the ZDN group. ConclusionIt was concluded that Zn-deficient diet causes abnormal morphology sperm and testicular oxidative stress in male mice. Abnormal morphology sperm caused by Zn-deficient diet are reversible, and Zn-normal diet can alleviate them.

Taurine Improves Sperm Mitochondrial Indices, Blunts Oxidative Stress Parameters, and Enhances Steroidogenesis and Kinematics of Sperm in Lead-Exposed Mice.

Lead (Pb) is a highly toxic heavy metal. Pb exposure could adversely affect many organs, including the male reproductive system. Oxidative stress and mitochondrial impairment play a fundamental role in the pathogenesis of Pb-induced male reproductive system injury. Taurine (TAU) is abundantly found in mammalian bodies. The positive effects of TAU on oxidative stress biomarkers and mitochondrial function have been reported. The current study evaluated the effects of TAU on Pb-induced reproductive toxicity. Mice received Pb (20mg/kg/day; gavage, 35 consecutive days). Then, sperm indices (quality and quantity) together with sperm kinetics, sperm mitochondrial parameters, testicular and sperm oxidative stress biomarkers, testis and plasma testosterone levels, and the expression of genes involved in the steroidogenesis process have been evaluated. Pb caused significant histopathological alterations and oxidative stress in male mice's reproductive system and sperm. Moreover, significant mitochondrial function impairment was evident in sperm isolated from Pb-treated mice. Pb exposure also suppressed the expression of StAR, 17β-HSD, CYP11A, and 3β-HSD genes in the male gonad. It was found that TAU (500 and 1000mg/kg) significantly improved oxidative stress biomarkers in both male gonads and gametes of Pb-treated mice. TAU also significantly restored sperm mitochondrial function and kinetics. The expression of genes involved in steroidogenesis was also higher in TAU-treated animals. These data suggest TAU as an effective agent against Pb-induced reproductive toxicity. The effects of TAU on oxidative stress markers, mitochondrial function, and the steroidogenesis process seem to play a fundamental role in its protective properties. Further studies are warranted to detect the precise protective effects of this amino acid in the reproductive system. Lead (Pb) is a toxic element that adversely affects the male reproductive system. Mitochondrial impairment and oxidative stress have a crucial role in the Pb-induced reproductive toxicity. Taurine (TAU) could considerably improve the reproductive toxicity induced by Pb via enhancing mitochondrial function and mitigating oxidative stress indices. ΔΨ, mitochondrial membrane potential; ATP, adenosine triphosphate.

Betaine attenuate chronic restraint stress-induced changes in testicular damage and oxidative stress in male mice

ScopeMale fertility and sperm quality are negatively affected by psychological stress. Chronic restraint stress (CRS) is a common psychological stress that has a negative effect on sperm. Betaine (BET), an active ingredient isolated from Lycium barbarum, has anti-oxidant, anti-inflammatory and other pharmacological activities. This study aims to explore whether betaine has a therapeutic effect on sperm deformity and vitality under CRS and its mechanism.Methods and resultsChronic restraint stress was induced in 8-week-old male C57BL/6 J mice by fixation for 6 h a day for 35 days. Mice were intraperitoneally injected with betaine (BET) or normal saline (NS) for 14 days. Thirty-five days later, the animals were sacrificed. The results showed that the detrimental effects of CRS on testes as evident by disrupted histoarchitecture, increased oxidative stress, inflammation and apoptosis that compromised male fertility. BET injections can reverse these symptoms.ConclusionsBET can improve spermatogenesis dysfunction caused by CRS, which may provide potential dietary guidance.Graphical abstract

Fucoidan Protects against Acute Sulfoxaflor-Induced Hematological/Biochemical Alterations and Oxidative Stress in Male Mice

Fucoidan is a sulfated polysaccharide which can be found among a number of macroalgea species. It has a broad spectrum of biological activities including anti-oxidant, anti-tumor, immunoregulation, anti-viral and anti-coagulant. The current study was performed to investigate possible protective effects of fucoidan for sulfoxaflor-induced hematological/biochemical alterations and oxidative stress in the blood of male Swiss albino mice. For this purpose, sulfoxaflor was administered at a dose of 15 mg/kg/day (1/50 oral LD50), and fucoidan was administered at a dose of 50 mg/kg/day by oral gavage alone and combined for 24 h and 7 days. Hematological parameters (RBC, HGB, HCT, MCV, MCH, MCHC, Plt, WBC, Neu, Lym and Mon), serum biochemical parameters (AST, ALT, GGT, LDH, BUN, Cre and TBil), and serum oxidative stress/antioxidant markers (8-OHdG, MDA, POC and GSH) were analyzed. The results indicated that sulfoxaflor altered hematological and biochemical parameters and caused oxidative stress in mice; fucoidan ameliorated some hematological and biochemical parameters and exhibited a protective role as an antioxidant against sulfoxaflor-induced oxidative stress.

Epigenetic Programming Reverses Cardiometabolic Dysfunctions and Modulates Hypothalamic Genes Involved in Oxidative Stress and Inflammation in Angiotensin II-Treated Male Mice

Cardiometabolic disease is a global health issue that affects millions of people worldwide. Environmental perinatal exposure affects the health outcomes of the offspring and determines their disease susceptibility later in life. Angiotensin-II (Ang-II) is a peptide known to cause vasoconstriction, elevated blood glucose levels and inflammation. Previously, we reported that perinatal exposure to a hypercaloric diet (HD) results in elevated blood pressure (BP), weight gain, fasting hyperglycemia and glucose intolerance only in male mice. In addition, subcutaneous infusion of a sub-pressor dose of Ang-II was associated with a normalization in fasting blood glucose levels and a reversal of glucose intolerance only in programmed male mice. We hypothesize that epigenetic programming blocks the deleterious effects of Ang-II by altering its inflammatory signaling pathway. C57BL6/J dams were fed HD or regular diet (RD) for 1 month before mating with RD-fed males. After weaning, offspring of HD dams (programmed) and of RD dams (controls) were maintained on RD until 3 months of age. Mice then underwent 24 h BP recording (telemetry) and were implanted with Ang-II osmotic pumps (200 ng/kg/min/2 weeks). BP (24 h) was recorded weekly for 2 weeks. Mice were then sacrificed and hypothalami were harvested for mRNA sequencing (Illumina NextSeq). Programmed mice had lower 24 h systolic BP levels compared to control males (area under the curve: 41844 ±263.2 vs. 44522 ±275.6; p<0.0001). For RNAseq analysis, data showed 62 differentially expressed genes (DEG) in programmed males compared to controls. Using iPathway analysis, we found that some of the DEG are correlated to cholinergic synapse pathway (p=0.005) and neuroactive ligand-receptor interaction pathway (p=0.003). Nicotinic acetylcholine alpha-7 receptor (Chrna7) gene, known for its anti-inflammatory and hypoglycemic effects was upregulated in programmed males (p=0.024). On the other hand, genes involved in metabolic pathways and oxidative stress were differentially expressed as well. Phospholipase A2 group 3 (Pla2g3) gene, known to be overexpressed in oxidative stress was downregulated in programmed males (p=0.04). Moreover, Thiosulfate sulfurtransferase (Tst) gene, an antioxidant enzyme and used as a marker for enhanced insulin sensitivity was upregulated (p=0.023) in programmed males. Interestingly, female mice did not show any changes in BP or gene expression between the two groups. In conclusion, perinatal exposure to HD alters the cardiovascular response to Ang-II possibly through the modulation of gene expression of Chrna7 gene and genes involved in oxidative stress. Future experiments will be investigating the signaling pathways used in epigenetic programming to affect inflammation and oxidative stress in male mice.

Effects of 2-MCPD on oxidative stress in different organs of male mice

2-Monochloropropane-1,3-diol (2-MCPD) and its isomer 3-monochloropropane-1,2-diol (3-MCPD) are widespread food contaminants. 3-MCPD has been classified as a non-genotoxic carcinogen, whereas very limited toxicological data are available for 2-MCPD. Animal studies indicate that heart and skeletal muscle are target organs of 2-MCPD. Oxidative stress may play a role in this process, and the potential of 3-MCPD to induce oxidative stress in vivo has already been demonstrated. To investigate the potential of 2-MCPD to induce oxidative stress in vivo, a 28-day oral feeding study in male HOTT reporter mice was conducted. This mouse model allows monitoring substance-induced oxidative stress in various target organs on the basis of Hmox1 promoter activation. Repeated daily doses of up to 100 mg 2-MCPD/kg body weight did not result in substantial toxicity. Furthermore, the highest dose of 2-MCPD had only minor effects on oxidative stress in kidney and testes, whereas brain, heart and skeletal muscle were not affected. Additionally, 2-MCPD caused only mild changes in the expression of Nrf2-dependent genes and only slightly affected the redox status of the redox-sensor protein DJ-1. Thus, the data indicate that 2-MCPD, in contrast to its isomer 3-MCPD, does not lead to a considerable induction of oxidative stress in male mice.

Time Restricted Feeding Reduces Vascular Damage and Oxidative Stress in Male Mice on a Chronic High Fat Diet

Irregular timing of food intake is known to influence risk for cardiometabolic disease. Studies in humans and animals demonstrate that a chronic high fat diet (HFD) leads to endothelial dysfunction and cardiovascular disease. We hypothesized that restricting food availability to the active period with a HFD leads to reduced vascular damage, increased nitric oxide synthase (NOS3) activation, and reduced oxidative stress. Mice (male 8‐week old, C57BL/6J) were given a normal diet (ND; 10% fat) or HFD (45% fat) for 20 weeks ad libitum. Time restricted feeding (TRF; food availability only during the active phase between ZT12 to ZT0 or 7 PM to 7 AM) was enforced in half of the HFD mice during the final 2 weeks of feeding. At the end of the study, aortae and plasma were collected at ZT5 and ZT17 in the middle of the inactive and active periods, respectively. 24 hour food intake was similar between ad lib and TRF mice. Aortic wall thickness was significantly increased in mice on HFD compared to ND (HFD: 76±5.1 μm; ND: 59±4.6 μm; n=6, p=0.03). Interestingly, aortic fibrosis was reduced by TRF in HFD mice (HFD: 18±2.3%; HFD+TRF: 11±1.9%; n=6, p=0.04). To assess NOS3 activation, Western blotting was used to measure pNOS3(S1177) and NOS3 abundance in aortae. At ZT5 pNOS3(S1177) abundance was not affected by TRF in HFD mice (HFD: 0.5±0.3 rdu, HFD+TRF: 0.7±0.1 rdu, n=4). TRF significantly increased pNOS3(S1177) abundance in HFD mice at ZT17 (HFD: 0.5±0.2 rdu, HFD+TRF: 2.1±0.6 rdu, n=4, p=0.06). Total NOS3 expression was unaffected by TRF at both time points. During the inactive period, endothelial‐dependent relaxation to acetylcholine was significantly impaired in HFD mice and improved by TRF (ND: 93±1.4%; HFD: 57±14%; HFD+TRF: 79±4.0%, n=5–11, ND vs HFD: p=0.01). Endothelial function was not different between groups in the active period. Endothelial‐independent relaxation was similar in all groups in both inactive and active periods. Plasma nitrite, a metabolite of NO, at ZT5 was unchanged between all groups. At ZT17 plasma nitrite was significantly decreased in HFD mice compared to ND mice and unaffected by TRF (HFD: 0.6±0.06 μM; HFD+TRF: 0.7±0.03 μM; ND: 1.1±0.2 μM; n=10–11, p=0.03). 8‐isoprostane, an indirect measure of oxidative stress, was significantly reduced by TRF in HFD mice at ZT5 (HFD: 159±31 ng/mL; HFD+TRF: 60±12 ng/mL, n=4–6, p=0.01), but not different between groups at ZT17. In conclusion, these results demonstrate that restricting timing of food intake improves vascular damage and decreases oxidative stress following diet‐induced obesity in a time‐dependent manner.Support or Funding InformationSupported by T32 DK007545, an AHA Postdoctoral Fellowship (18POST34070051) to PP, an AHA Predoctoral Fellowship (18PRE33990345) to DZ, P01 HL069999 to JSP and DMP, and P01 HL136267 to JSP, EWI, and DMP.

Renal protective effects of grape seed extract treatment against Eltroxin-induced hyperthyroidism, kidney damage, and oxidative stress in male mice.

The present study aimed to investigate the influence of grape seed extract (GSE) in renal toxicity, oxidative stress, and Bcl-2 expressions in Eltroxin-induced hyperthyroidism to male mice. GSE was evaluated through oral administration to male mice at dose 50mg/kg daily for 3 consecutive weeks. Eltroxin (100μg/kg) was administered to mice for 3weeks, and the mice were posttreated with GSE for another 3weeks. Results revealed that GSE administered to normal mice did not produce any signs of toxicity and did not cause any biochemical or histopathological changes. Posttreatment of Eltroxin-induced hyperthyroidism mice with GSE daily for 3weeks improved all examined biochemical or histopathological features. Oral GSE can significantly normalize the elevated level of T3 and T4 in hyperthyroidism animals and elevated the reduced levels of TSH. Moreover, serum urea, creatinine, and electrolyte levels were significantly improved. GSE showed a potent antioxidant capacity in all oxidative stress markers assays (TBARS, reduced GSH, GST, SOD, and CAT) of kidney tissue homogenates. Furthermore, histopathological examination of kidney tissue of Eltroxin + GSE-treated group confirms the potential nephroprotective effect of GSE through increasing the anti-apoptotic marker Bcl-2.

STUDI PRELIMINARI TENTANG PENGARUH D-GALAKTOSA DALAM MENGINDUKSI STRES OKSIDATIF PADA MENCIT JANTAN GALUR OUTBRED FK USU

Abstract&#x0D; &#x0D; Oxidative stress occurs due to imbalance of free radicals over antioxidant level in the body. This condition causes lipid peroxidation and DNA damage. D-Galaktosa is The mechanism of oxidative stress induced by d-galactose occurs in the subcellular, especially in the brain's mitochondria. Increasing the concentration of d-galaktosa is oxidized by galaktosa oxidase to form hydrogen peroxide (H202) which causes a decrease in superoxide dismutase (SOD). H202 reacts with reduced iron and forms hydroxide ions (OH-).&#x0D; Objective: The aim of this study was to determine the effect of d-galaktosa induction on oxidative stress levels (MDA) in male mice.&#x0D; Methods: Methods of samples of mice given d-galaktosa and blood collection from the heart were carried out at the Pharmacology Laboratory of the Faculty of Medicine, University of North Sumatra.&#x0D; Results: The results showed that administration of d-galaktosa, through intraperitonial injection every day for 6 weeks, had an effect on the levels of oxidative stress in male mice.&#x0D; Conclusion: The results of this study indicate that administration of d-galaktosa, through intraperitonial injection every day for 6 weeks, has an effect on levels of oxidative stress in male mice.&#x0D;

Down-regulation of Cav1.3 in auditory pathway promotes age-related hearing loss by enhancing calcium-mediated oxidative stress in male mice.

In this study, age related Cav1.3 expression in cochlea and auditory cortex of C57BL/6J male mice was evaluated. It was found that the expression of Cav1.3 in cochlea decreased with aging whereas this phenomenon was not observed in neuron of auditory cortex. The correlation between decreased expression of Cav1.3 and age-related hearing losses was studied in vitro, after Cav1.3 was knocked out, the rate of apoptosis of hair cells increased after being subjected to ROS stresses, accompanied with enhanced senescence. Further, Cav1.3 knock down also interfered with the electrophysiology of hair cells. The effect was further confirmed in vivo, after Cav1.3 knocked down by injection of AAV, hearing impairment was observed in C57BL/6J male mice subjected to senescence and this was accompanied by increased loss of hair cells in cochlea. The effect was further confirmed in 3D organ culture, increased loss of hair cells after Cav1.3 was knocked down under ROS stresses.Mechanistically, Cav1.3 knock out resulted in decreased intracellular calcium which subsequently reduced the inactivation of ROS from complex I, and finally resulted in increased intracellular ROS and enhanced senescence.Collectively, these findings confirmed that Cav1.3 could protect cells in auditory pathway from oxidative stresses, and decreased expression of Cav1.3 in auditory pathway could contribute to hearing losses by enhancement of calcium-mediated oxidative stress.

Astaxanthin prevents the methotrexate-induced reproductive toxicity by targeting oxidative stress in male mice

The future fertility of cancer patients after treatment is a serious concern amongst young cancer patients. Such chemotherapeutic agents as Methotrexate (MTX), a folic acid antagonist can cause long-term or permanent gonadal toxicity in male patients. Oxidative stress is a contributing mechanism to MTX-induced testicular damage. In the past decade, several studies have investigated the use of natural antioxidant agents to prevent the side effects of MTX. Astaxanthin (AST), a red-orange xanthophyll carotenoid, owns various clinical benefits and pharmacological effects including antioxidant, anti-tumor, anti-cancer, anti-diabetic, and anti-inflammatory properties. Since there has been no study so far in the literature on the effects of AST on MTX-induced testicular dysfunction, the present study evaluated the ameliorating effect of AST against MTX-induced testicular dysfunction. Biometric and semen parameters as well as, biochemical markers of oxidative stress were measured. Compared to the control group, MTX-treated group showed a significant decrease in sperm count, motility, viability, morphology, superoxide dismutase (SOD) and catalase (CAT) activities, and a significant increase in MDA levels. Pretreatment with AST for six consecutive days before MTX administration prevented these oxidative parameters. Thus, the current results suggest that MTX seems to impair the male fertility through oxidative damage in one hand, and AST pretreatment might improve the male fertility by preventing oxidative stress-induced fertility disorders, on the other hand. However, AST pretreatment might also protect germ cells against MTX-induced oxidative stress.

Antidepressant-like effect of a new selenium-containing compound is accompanied by a reduction of neuroinflammation and oxidative stress in lipopolysaccharide-challenged mice.

Organoselenium compounds and indoles have gained attention due to their wide range of pharmacological properties. Depression is a recurrent and disabling psychiatric illness and current evidences support that oxidative stress and neuroinflammation are mechanisms underlying the pathophysiology of this psychiatric condition. Here, we evaluated the effect of 3-((4-chlorophenyl)selanyl)-1-methyl-1H-indole (CMI) in lipopolysaccharide (LPS)-induced depressive-like behaviour, neuroinflammation and oxidative stress in male mice. CMI pre-treatment (20 and 50 mg/kg, intragastrically) significantly attenuated LPS (0.83 mg/kg, intraperitoneally)-induced depressive-like behaviour in mice by reducing the immobility time in the tail suspension test (TST) and forced swimming test (FST). CMI pre-treatment ameliorated LPS-induced neuroinflammation by reducing the levels of interleukin (IL)-1β, IL-4 and IL-6 in the hippocampus and prefrontal cortex, as well as markers of oxidative damage. Additionally, we investigated the toxicological effects of CMI (200 mg/kg, i.g.) in the liver, kidney and brain through determination of the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), δ-aminolevulinate dehydratase (δ-ALA-D) and creatinine levels. These biomarkers were not modified, indicating the possible absence of neuro-, hepato- and nephrotoxic effects. Our results suggest that CMI could be a therapeutic approach for the treatment of depression and other neuropsychiatric disorders associated with inflammation and oxidative stress.

Mitochondrial reactive oxygen species suppress humoral immune response through reduction of CD19 expression in B cells in mice

Reactive oxygen species (ROS) are implicated in the modulation of diverse processes including immune responses. To evaluate the effects of metabolic ROS produced by mitochondria on B-cell function and development, we created transgenic (Tg) mice expressing a phosphorylation-defective mutant of succinate dehydrogenase A in B cells (bSDHAY215F ). Splenic B cells in male, but not female, bSDHAY215F mice produced three times more ROS than those in the control mice, and had decreased production of IgM, IgG1 , and IgG3 , and affinity maturation of IgG1 against T-cell-dependent antigens. Following immunization, the male bSDHAY215F mice further displayed suppressed germinal center (GC) formation, and proliferation of GC B cells. Signaling analysis revealed defects in the intrinsic BCR responses, such as activation of Lyn, Btk, and PLCγ2, thus resulting in reduced intracellular Ca2+ mobilization. Notably, the expression levels of B-cell co-receptor CD19 and its interaction with Lyn after BCR ligation were significantly reduced in B cells from male bSDHAY215F mice. These results suggest that mitochondrial ROS suppress humoral immune responses through reduction of CD19 expression and resultant BCR signaling in B cells. Therefore, B-cell immunity may be more labile to oxidative stress in male mice than in female mice.

Ethanolic Extract of Madhuhari Ameliorates Diabetes–Induced Oxidative Stress in Male Mice

Ethanolic Extract of Madhuhari Ameliorates Diabetes–Induced Oxidative Stress in Male Mice

Silica nanoparticles induce reversible damage of spermatogenic cells via RIPK1 signal pathways in C57 mice.

The reproductive toxicity of silica nanoparticles (SiNPs) is well known, but the underlying mechanism is still not clear. To investigate the toxic mechanism of SiNPs on spermatogenic cells, 60 C57 male mice were randomly and equally divided into three groups (the control group, the saline control group, and the SiNPs group) with two observed time points (45 days and 75 days). The mice in the SiNPs group were administered with SiNPs 2 mg/kg diluted in normal saline, and the mice of the saline control group were given equivoluminal normal saline by tracheal perfusion every 3 days for 45 days (in total 15 times). The control group mice were bred without treatment. In each group, a half number of the mice were sacrificed on the 45th day after the first dose, and the remaining half were sacrificed on the 75th day. The results showed that SiNPs increased the malformation of sperms and decreased the motility and concentration of sperms in epididymis on the 45th day after the first dose. SiNPs induced oxidative stress in testis and led to apoptosis and necroptosis of the spermatogenic cells. Furthermore, SiNPs increased the expression of Fas/FasL/RIPK1/FADD/caspase-8/caspase-3 and RIPK3/MLKL on the 45th day after the first dose. However, compared with the saline control group, the index of sperms and the expression of Fas/FasL/RIPK1/FADD/caspase-8/caspase-3/RIPK3/MLKL showed no significant changes in the SiNPs group on the 75th day after the first dose. These data suggested that SiNPs could induce apoptosis and necroptosis in the spermatogenic cells by activating the RIPK1 pathway resulting from oxidative stress in male mice. SiNPs-induced damage recovered on the 75th day after the first dose, which suggested that SiNPs-induced toxicity is reversible.

Lower susceptibility of female mice to acetaminophen hepatotoxicity: Role of mitochondrial glutathione, oxidant stress and c-jun N-terminal kinase

Acetaminophen (APAP) overdose causes severe hepatotoxicity in animals and humans. However, the mechanisms underlying the gender differences in susceptibility to APAP overdose in mice have not been clarified. In our study, APAP (300mg/kg) caused severe liver injury in male mice but 69–77% lower injury in females. No gender difference in metabolic activation of APAP was found. Hepatic glutathione (GSH) was rapidly depleted in both genders, while GSH recovery in female mice was 2.6 fold higher in the mitochondria at 4h, and 2.5 and 3.3 fold higher in the total liver at 4h and 6h, respectively. This faster recovery of GSH, which correlated with greater induction of glutamate-cysteine ligase, attenuated mitochondrial oxidative stress in female mice, as suggested by a lower GSSG/GSH ratio at 6h (3.8% in males vs. 1.4% in females) and minimal centrilobular nitrotyrosine staining. While c-jun N-terminal kinase (JNK) activation was similar at 2 and 4h post-APAP, it was 3.1 fold lower at 6h in female mice. However, female mice were still protected by the JNK inhibitor SP600125. 17β-Estradiol pretreatment moderately decreased liver injury and oxidative stress in male mice without affecting GSH recovery. Conclusion: The lower susceptibility of female mice is achieved by the improved detoxification of reactive oxygen due to accelerated recovery of mitochondrial GSH levels, which attenuates late JNK activation and liver injury. However, even the reduced injury in female mice was still dependent on JNK. While 17β-estradiol partially protects male mice, it does not affect hepatic GSH recovery.

Effects of ginsenosides-Rb1 on exercise-induced oxidative stress in forced swimming mice.

Background:The fleshy root of Panax ginseng C.A. Meyer (ginseng) is one of the most well-known and valued herbs in traditional Chinese medicine. Ginsenosides are considered mainly responsible for the pharmacological activities of ginseng. The purpose of this study was to investigate the effects of ginsenoside-Rb1 (G-Rb1) on swimming exercise-induced oxidative stress in male mice.Materials and Methods:A total of 48 animals were randomly divided into four groups, with twelve mice in each group. The first, second and third groups were designed as G-Rb1 treatment groups, got 25, 50 and 100 mg/kg bodyweight of G-Rb1, respectively. The fourth group was designed as the control group, got physiologic saline. The mice were intragastrically administered once daily for 4 weeks. The weight-loaded forced swimming test was conducted on the final day of experimentation. Then the exhaustive swimming time, blood lactate, serum creatine kinase (CK), malondialdehyde (MDA) and antioxidant enzymes in liver of mice were measured.Results:The results showed that G-Rb1 could prolong the exhaustive swimming time and improve exercise endurance capacity of mice, as well as accelerate the clearance of blood lactate and decrease serum CK activities. Meanwhile, G-Rb1 could decrease MDA contents and increase superoxide dismutase, catalase, glutathione peroxidase activities in liver of mice.Conclusions:The study suggested that G-Rb1 possessed protective effects on swimming exercise-induced oxidative stress in mice.

Study theEffects of Glutathione (GSH) on Blood Glucose Level in Diabetic Male Mice

Investigated effects of daily injections intra venially (IV) of glutathione (GSH) (11.37 mg/mice)forthe periods 10 and 20 days,for healthy mice and diabetic male micecompared them with control group and diabetic non treated male mice, blood sugar was testedfor fasting mice, induced diabetic, to study the glutathione daily injections e3.ffects on the blood sugar level, total glutathione assay in different body organs and finally study the expression level of the glutathione redox system enzymes glutathione reductase (GR) and glutathione peroxidase (GPx) in pancreas, spleen, testis, and epididymus by the Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). The experiment outcomes for the glutathione daily injection for the diabetic induced male mice high sugar level significantly decreased. Moreover, the oxidative stress in diabetic male mice leads to depletion of total glutathione level in body organs. Finally, Diabetes causes high oxidative stress in male mice which leads to increase expressions of antioxidants enzymes GR and GPx in pancreas, epididymus and testis.

Exposure to bifenthrin causes immunotoxicity and oxidative stress in male mice

Bifenthrin (BF) is one of the most commonly used pesticides among the synthetic pyrethroids. The effects of BF exposure on the induction of immunotoxicity and oxidative stress were studied both in adolescent and adult male ICR mice. Both the weights of the spleen and thymus decreased significantly in the adolescent mice when they were treated with 20 mg/kg BF for 3 weeks. We found that the 3-week oral administration of BF during puberty increased the transcriptional levels of the genes TNF and IL2 in the spleen and IL2 as well as IL4 in the thymus. The effect of BF exposure on the induction of oxidative stress was also studied in serum and liver samples. The total antioxidant capacity and activity of superoxide dismutase were altered significantly in the serum of the 20 mg/kg BF-treated adolescent mice, and the activity of glutathione peroxidase (GPX) decreased significantly in the serum of adolescent and adult mice after 3 weeks of oral administration of 20 mg/kg BF. Compared to serum, hepatic GSH content increased significantly in both the adolescent and adult mice exposed to 20 mg/kg BF; hepatic CAT and GPX activities were altered significantly, even in adolescent mice, after treatment with 10 mg/kg BF. Taken together, the results of this study suggest that exposure to BF, especially during puberty, has the potential to induce immunotoxicity accompanied by oxidative stress in male mice. These findings will help in elucidating the mechanism of toxicity induced by BF in mice.

Antioxidant Activities of Various Extracts from Artemisisa selengensis Turcz (LuHao)

The antioxidant activities of the various extracts and fractions from the herbs of Artemisia selegensis Turcz (AST) were investigated by in vitro and in vivo assays. FRAP, DPPH and ABTS assays were used to evaluate the antioxidant activities of the extracts/fractions in vitro. The effect of water extract (WE) in reducing oxidative stress in male mice was evaluated. Phenolic acid compounds contribute significantly to the antioxidant activity. From the results of three in vitro antioxidant assays, WE was found to have the highest antioxidant activity, and among the WE subfractions, the water soluble fraction has a significant antioxidant activity. The in vivo antioxidant assay results showed that high doses of WE significantly decrease the MDA level compared to normal diet and D-(+) galactose group (p < 0.05), and the SOD activity of mice given a high dose of WE was the highest. These in vitro and in vivo studies demonstrated that the extracts, especially the WE from AST, have significant antioxidant and free radical scavenging activities. In summary, we propose that AST could be potentially used as a rich source of natural antioxidants.