Establishment of a Mouse Asthenospermia Model through Triggering DGalactose Mediated Oxidative Stress Injury

Author(s):  
Nanjun Liu ◽  
Qianxing Wang ◽  
Lin Li ◽  
Jian Lu

Background: Asthenospermia is defined as forward motility of sperm less than 32%. Aim/Objective: This study aimed to establish mouse model of asthenospermia through triggering D-galactose mediated oxidative stress. Materials and methods: Total of 40 Kunming male mice were randomly divided into control group, low-dose group (administrating D-galactose at 60 mg/kg), high-dose group (administrating D-galactose at 120 mg/kg) and high-dose+feed addition group (administrating D-galactose at 120 mg/kg together with oral D-galactose). The testicular weight, testicular organ coefficient, sperm viability, sperm concentration and survival rate of tail of epididymis were measured. Oxidative damage of D-galactose to reproductive system of mice was evaluated by measuring superoxide dismutase (SOD) and malondialdehyde (MDA) in testicular homogenate of mice. Findings: The sperm motility, motility rate, concentration and survival rate of low-dose, high-dose and high-dose+feed addition group were decreased, compared to that in control group. However, there were significant difference between highdose group/high dose+feed group and control group (p<0.05). The forward motile sperm motility rate and total motility rate accorded with critical criteria of asthenospermia. Comparing with the control group, activity of SOD of model group mice significantly decreased, and MDA concentration significantly increased (p<0.05), excepting for low-dose versus control group for SOD activity. This suggests that testicular tissues suffered from oxidative damage. Conclusions: This study successfully established a mouse asthenospermia model through D-galactose mediated oxidative stress injury. The establishment of asthenospermia model in this study would provide a new promising insight and act as a potential approach for studying asthenospermia in vivo levels.

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.


2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Tao Hong ◽  
Long-Xue Li ◽  
Xiao-ping Han ◽  
Jing-liang Shi ◽  
Cai-yun Dan ◽  
...  

In this study, the effects of Astragalus membranaceus oral solution on lifespan and learning and memory abilities of honey bees were evaluated. Two groups of bees were fed with sucrose syrup (50%) containing low dose (1.33%) and high dose (13.3%) of A. membranaceus oral solution, respectively. The proboscis extension response (PER) analysis was applied to examine the learning and memory capabilities of bees. Two genes related to memory formation in honey bees were determined by real-time PCR. High dose (13.3%) of A. membranaceus significantly decreased the mean lifespan of bees compared to the bees fed with low dose (1.33%) and control bees. No significant differences in lifespan of bees were found between low-dose-fed bees and control bees. The results of PER experiments showed apparent improvement in the memorizing ability of the high-dose group (in comparison with the control group). Moreover, the relative expression levels of Nmdar1 in the low-dose group and control group were significantly lower than those in the high-dose group. It is preliminarily concluded that A. membranaceus has an adverse effect on the mean lifespan of honey bees but might be helpful in strengthening memories.


2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Kehua Jiang ◽  
Jianxin Hu ◽  
Guangheng Luo ◽  
Dalong Song ◽  
Peng Zhang ◽  
...  

Oxalate and calcium are the major risk factors for calcium oxalate (CaOx) stone formation. However, the exact mechanism remains unclear. This study was designed to confirm the potential function of miR-155-5p in the formation of CaOx induced by oxalate and calcium oxalate monohydrate (COM). The HK-2 cells were treated by the different concentrations of oxalate and COM for 48 h. We found that oxalate and COM treatment significantly increased ROS generation, LDH release, cellular MDA levels, and H2O2 concentration in HK-2 cells. The results of qRT-PCR and western blot showed that expression of NOX2 was upregulated, while that of SOD-2 was downregulated following the treatment with oxalate and COM in HK-2 cells. Moreover, the results of miRNA microarray analysis showed that miR-155-5p was significantly upregulated after oxalate and COM treated in HK-2 cells, but miR-155-5p inhibitor treatment significantly decreased ROS generation, LDH release, cellular MDA levels, and H2O2 concentration in HK-2 cells incubated with oxalate and COM. miR-155-5p negatively regulated the expression level of MGP via directly targeting its 3′-UTR, verified by the Dual-Luciferase Reporter System. In vivo, polarized light optical microphotography showed that CaOx crystal significantly increased in the high-dose oxalate and Ca2+ groups compared to the control group. Furthermore, IHC analyses showed strong positive staining intensity for the NOX-2 protein in the high-dose oxalate and Ca2+-treated mouse kidneys, and miR-155-5p overexpression can further enhance its expression. However, the expression of SOD-2 protein was weakly stained. In conclusion, our study indicates that miR-155-5p promotes oxalate- and COM-induced kidney oxidative stress injury by suppressing MGP expression.


2021 ◽  
Vol 70 (2) ◽  
pp. 235-243
Author(s):  
TONG TONG ◽  
XIAOHUI NIU ◽  
QIAN LI ◽  
YUXI LING ◽  
ZUMING LI ◽  
...  

Lactobacillus plantarum BW2013 was isolated from the fermented Chinese cabbage. This study aimed to test the effect of this strain on the gut microbiota in BALB/c mice by 16S rRNA amplicon sequencing. The mice were randomly allocated to the control group and three treatment groups of L. plantarum BW2013 (a low-dose group of 108 CFU/ml, a medium-dose group of 109 CFU/ml, and a high-dose group of 1010 CFU/ml). The weight of mice was recorded once a week, and the fecal samples were collected for 16S rRNA amplicon sequencing after 28 days of continuous treatment. Compared with the control group, the body weight gain in the treatment groups was not significant. The 16S rRNA amplicon sequencing analysis showed that both the Chao1 and ACE indexes increased slightly in the medium-dose group compared to the control group, but the difference was not significant. Based on PCoA results, there was no significant difference in β diversity between the treatment groups. Compared to the control group, the abundance of Bacteroidetes increased in the low-dose group. The abundance of Firmicutes increased in the medium-dose group. At the genus level, the abundance of Alloprevotella increased in the low-dose group compared to the control group. The increased abundance of Ruminococcaceae and decreased abundance of Candidatus_Saccharimonas was observed in the medium-dose group. Additionally, the abundance of Bacteroides increased, and Alistipes and Candidatus_Saccharimonas decreased in the high-dose group. These results indicated that L. plantarum BW2013 could ameliorate gut microbiota composition, but its effects vary with the dose.


2020 ◽  
Author(s):  
Randi Ugleholdt ◽  
Åse Krogh Rasmussen ◽  
Pernille Agnete Heldager Haderslev ◽  
Bjarne Kromann-Andersen ◽  
Claus Larsen Feltoft

Abstract Background. Alpha-receptor blockade is the mainstay in preoperative treatment of patients with pheochromocytoma and paraganglioma (PPGL). However, evidence regarding optimal dosage regimen is lacking. This study compares the per- and postoperative hemodynamics in patients pre-treated with a high or low dose of phenoxybenzamine. Methods. 30 consecutive patients with PPGL undergoing laparoscopic adrenalectomy were identified retrospectively. All were pretreated with phenoxybenzamine but at two separate endocrine departments aiming at different blood pressure target. End-dosage of phenoxybenzamine differed significantly between departments with 14 patients receiving a high dose regimen and 16 a low dose regimen. As a control group, we included 42 patients undergoing laparoscopic adrenalectomy for other reasons. Primary purpose was to compare per- and postoperative hemodynamics in the high and low dose groups. Secondly, to compare these endpoints to the control group. Results. Baseline characteristics did not differ between the phenoxybenzamine treated groups. The high dose group had less intra-operative systolic and diastolic blood pressure fluctuation (p = 0.03) and less periods with heart rate above 100 bpm (p = 0.04) as compared to the low dose group. Use of intravenous fluids were similar between the two groups. However, postoperatively, more intravenous fluids were administered in the high dose group. Overall, the control group was more hemodynamic stable as compared to either group treated for PPGL. Conclusions. High dose phenoxybenzamine improves per-operative hemodynamic stability but causes a higher postoperative requirement for intravenous fluids. Overall, PPGL surgery is related to greater hemodynamic instability compared to adrenalectomy for other reasons.


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Won Park ◽  
Jeffrey R. Curtis ◽  
Min Jung Kim ◽  
Hajeong Lee ◽  
Yeong Wook Song ◽  
...  

Abstract Objectives To investigate the incidence of pneumocystis pneumonia (PCP) and its risk factors in patients with rheumatic disease receiving non-high-dose steroid treatment, along with the risks and benefits of PCP prophylaxis. Methods This study included 28,292 treatment episodes with prolonged (≥ 4 weeks), non-high-dose steroids (low dose [< 15 mg/day, n = 27,227] and medium dose [≥ 15 to < 30 mg/day, n = 1065], based on prednisone) over a 14-year period. Risk factors for PCP and prophylactic effect of trimethoprim–sulfamethoxazole (TMP-SMX) were investigated if the 1-year incidence rate (IR) of PCP in each dose group was > 0.1/100 person-years. Cox regression with LASSO was used for analysis. Results One-year PCP IR in the low-dose group was 0.01 (95% CI 0.001–0.03)/100 person-years, and only the medium-dose group showed eligible PCP IR for further analysis. In the medium-dose group, prophylactic TMP-SMX was administered in 45 treatment episodes while other episodes involved no prophylaxis (prophylaxis group vs. control group). In 1018.0 person-years, 5 PCP cases occurred exclusively in the control group, yielding an IR of 0.5 (0.2–1.2)/100 person-years. Concomitant steroid-pulse treatment and baseline lymphopenia were the most significant risk factors for PCP. Treatment episodes with at least one of these factors (n = 173, high-risk subgroup) showed higher 1-year PCP IR (3.4 (1.1–8.0)/100 person-years), while no PCP occurred in other treatment episodes. TMP-SMX numerically reduced the risk (adjusted HR = 0.2 (0.001–2.3)) in the high-risk subgroup. The IR of adverse drug reactions (ADRs) related to TMP-SMX was 41.5 (22.3–71.6)/100 person-years, including one serious ADR. The number needed to treat with TMP-SMX to prevent one PCP in the high-risk subgroup (31 (17–226)) was lower than the number needed to harm by serious ADR (45 (15–∞)). Conclusion Incidence of PCP in patients with rheumatic diseases receiving prolonged, medium-dose steroids depends on the presence of risk factors. Prophylactic TMP-SMX may have greater benefit than potential risk in the high-risk subgroup.


1991 ◽  
Vol 69 (6) ◽  
pp. 812-817 ◽  
Author(s):  
Hoshiar Abdollah ◽  
F. James Brennan ◽  
Sandra Jimmo ◽  
James F. Brien

The relationship between the antiarrhythmic effect of amiodarone and its myocardial concentration was studied in dogs with 1-week-old myocardial infarction and reproducibly inducible sustained ventricular tachycardia or ventricular fibrillation. Three groups of animals (n = 10/group) received amiodarone, 40 mg∙kg−1∙day−1 (low-dose amiodarone), amiodarone 60 mg∙kg−1∙day−1 (high-dose amiodarone), or no amiodarone (control group). After 1 week of treatment, programmed electrical stimulation was repeated, and plasma and myocardial amiodarone and desethylamiodarone concentrations were measured. In the control group, sustained ventricular tachycardia or ventricular fibrillation was induced in six dogs (p = NS) when compared with baseline data. In the low-dose amiodarone group, sustained ventricular tachycardia or ventricular fibrillation was induced only in two dogs after 1 week of treatment (p < 0.01 vs. baseline data). Sustained ventricular tachycardia or ventricular fibrillation was induced in seven dogs after treatment with high-dose amiodarone (p = NS vs. baseline data). Plasma amiodarone concentration in the low-dose amiodarone group (2.54 ± 1.9 μg/mL) was significantly less (p < 0.01) than that in the high-dose amiodarone group (4.64 ± 1.66 μg/mL). Similarly, the plasma desethylamiodarone in the low-dose amiodarone group (0.32 ± 0.16 μg/mL) was significantly less (p < 0.001) than that in the high-amiodarone dose group (0.56 ± 0.23 μg/mL). The myocardial amiodarone concentration in the low-dose amiodarone group (49.7 ± 23.1 μg/g) was significantly lower (p < 0.001) than that in the high-dose group (98.4 ± 32.1 μg/g). There was no significant difference in the myocardial desethylamiodarone concentrations between the two treatment groups (25.1 ± 12.2 μg/g in the low-dose amiodarione group vs. 37.4 ± 16.4 μg/g in the high-dose amiodarone group). These data show that the high-dose amiodarone regimen, which produced high myocardial amiodarone concentration, didn't suppress sustained ventricular arrhythmias.Key words: amiodarone, ventricular arrhythmias, plasma and myocardial drug concentrations.


2014 ◽  
Vol 955-959 ◽  
pp. 744-747
Author(s):  
Lin Liu ◽  
Jia Yi Xia ◽  
Ju Huo ◽  
Zhao Ying

Object: The antioxidant dose-effect relationship and the mechanism of Xiongma Dripping Pills were study to explore the protective effects of oxidative damage in PC12 cells of different doses of Xiongma Dripping Pills containing serum. Method: Oxidative stress injury model of PC12 cells was established by peroxide hydrogen (H2O2), sodium nitroprusside (SNP), content and cell culture supernatant lactate dehydrogenase (LDH) and the liquid content of glutathione peroxidase (GSH-PX) were detected by chemical colorimetric determination. Results: There was a plasma concentration peaked in Xiongma Dripping Pills 8 times (6g•kg-1) dose group, ferulic acid plasma concentration was 10.59 ± 2.92, the plasma concentration gastrodin 18.13 ± 4.63. H2O2 and SNP could cause injury in PC12 cells, and increased LDH leakage, reduce the content of GSH-PX (P<0.01). Gung Ma the Dripping Pills can reduce LDH leakage, increase the content of GSH-PX. Xiongma Dripping Pills 8-fold dose group content is the most significant.Conclusion: There was a significant protective effect on Xiongma Dripping Pills serum containing H2O2 and SNP induced oxidative damage of PC12 cells and its mechanism was relevant with clearing the free radicals, enhanceing antioxidant enzyme activity in vivo. There was the most significant effect on Xiongma Dripping Pills 8-fold dose group, and there was positive correlation on plasma concentration and pharmacological effects.


2021 ◽  
Vol 37 (5) ◽  
pp. 251-259
Author(s):  
Xia Wang ◽  
Xubo Shen ◽  
Lei Chen ◽  
Qin Yu ◽  
Shimin Xiong ◽  
...  

This study investigated hepatic oxidative damage in rats following long-term manganese (Mn) exposure and clarified the underlying mechanisms. Forty-eight rats (SPF, male) were randomly assigned to receive low (10 mg/kg, n = 16) or high doses of Mn (50 mg/kg, n = 16) or sterilized distilled water (control group, n = 16). Rats were euthanized after 12 months, and liver Mn levels and histopathological changes were determined. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver malondialdehyde (MDA), glutathione peroxidase (GSH-PX), nuclear factor E2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinine oxidoreductase-1 (NQO1) levels were also determined. The Mn concentration and relative liver weights were significantly higher in the high-dose Mn group than in the control and low-dose Mn exposure groups. Low-dose Mn exposure resulted in mild expansion of hepatic sinuses and intact nuclei, whereas high-dose exposure led to pathological alterations in hepatocytes. High-dose Mn treatment significantly increased AST, ALT, and MDA activities and decreased GSH-PX activity. Additionally, liver Nrf2, HO-1, and NQO1 protein expression were markedly reduced by Mn exposure. Under the study conditions, long-term low-dose Mn exposure resulted in slight pathological changes in liver structure, but high-dose Mn exposure affected both liver structure and function, which might be related to the inhibition of Nrf2 expression, suppression of the transcription of its underlying antioxidant genes, and down regulation of the corresponding proteins. Consequently, the antioxidant capacity in the rat liver was weakened.


Sign in / Sign up

Export Citation Format

Share Document