scholarly journals Systematic evaluation of CdSe/ZnS Quantum Dots toxicity on the reproduction and offspring health in male BALB/c mice

2020 ◽  
Author(s):  
Li Li ◽  
Xiaotan Lin ◽  
Tingting Chen ◽  
Kan Liu ◽  
Zhiwen Yang ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Body Weight ◽  
Early Stage ◽  
Sperm Quality ◽  
Systematic Evaluation ◽  
High Dose ◽  
Male Mice ◽  
Organ Index ◽  
Acrosome Integrity ◽  
Offspring Health

Abstract Background: Increased applications of quantum dots (QDs) in biomedical field have aroused attention for their potential toxicological effects. Although many studies have been carried out on the toxicity of QDs, their effects on reproductive and development are still unclear. In this study, we systematically evaluated the male reproductive toxicity and developmental toxicity of CdSe/ZnS QDs in BALB/c mice.Results: The male mice were injected intravenously with CdSe/ZnS QDs at the dosage of 2.5 mg/kg BW or 25 mg/kg BW, respectively, and the survival status, biodistribution of QDs in testes, serum sex hormone levels, histopathology, sperm motility and acrosome integrity was measured on Day 1, 7, 14, 28 and 42 after injection. On Day 35 after treatment, male mice were housed with non-exposed female mice, and then offspring number, body weight, organ index and histopathology of major organs, blood routine and biochemical tests of offspring were measured to evaluate the fertility and offspring health. The results showed that CdSe/ZnS QDs could rapidly distribute in the testis, and the fluorescence of QDs could still be detected on Day 42 post-injection. QDs had no adverse effect on the structure of testis and epididymis, but high-dose QDs could induce apoptosis of Leydig cells in testis at an early stage. No significant differences in survival of state, body weight organ index of testis and epididymis, sex hormones levels, sperm quality, sperm acrosome integrity and fertility of male mice were observed in QDs exposed groups. However, the development of offspring was obviously influenced, which was mainly manifested in the slow growth of offspring, changes of organ index of main organs, and the abnormality of liver and kidney function parameters.Conclusion: Our findings revealed that CdSe/ZnS QDs were able to cross the blood-testis barrier (BTB), produce no discernible toxic effects on the male reproductive system, but could affect the healthy growth of future generations to some extent. In view of the broad application prospect of QDs in biomedical fields, our findings might provide insight into the biological safety evaluation of the reproductive health of QDs.

scholarly journals Evaluation of the effective dose of amygdalin for the improvement of antioxidant gene expression and suppression of oxidative damage in mice

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9232
Author(s):  
Sarah Albogami ◽  
Aziza Hassan ◽  
Nibal Ahmed ◽  
Alaa Alnefaie ◽  
Afnan Alattas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Body Weight ◽  
High Dose ◽  
Male Mice ◽  
Antioxidant Gene ◽  
Oxidative Balance ◽  
Antioxidant Gene Expression ◽  
Medium Dose

Background Little is known regarding the toxic and therapeutic doses of amygdalin. Treatment regimens and schedules can vary between humans and animal models, and there have been reports of cyanide toxicity due to amygdalin use. Objective The aim of this study was to evaluate the effect of different doses of amygdalin on antioxidant gene expression and suppression of oxidative damage in mice. Methods Forty adult male mice were divided randomly into four groups (n = 10) as follows and treated orally for two weeks: a control group treated with saline solution, a group treated with amygdalin at 200 mg/kg body weight, a group treated with amygdalin at 100 mg/kg body weight, and a group treated with amygdalin at 50 mg/kg body weight. Liver and testis samples were collected for gene expression, biochemical and histopathological analyses. Results The mice treated with medium-dose amygdalin (100 mg/kg) showed upregulated mRNA expression of glutathione peroxidase (P < 0.01) and superoxide dismutase (P < 0.05) and significantly decreased lipid peroxidation (P < 0.05) in hepatic and testicular tissues compared to those in the untreated groups (controls), with mild histopathological effects. The mice treated with high-dose of amygdalin (200 mg/kg) showed downregulated mRNA expression of glutathione peroxidase and superoxide dismutase (P < 0.01) and significantly increased lipid peroxidation (P < 0.05) in both hepatic and testicular tissues compared to those in the untreated groups (controls), with an apparent effect at the histopathological level. No effects were observed in the mice treated with low-dose amygdalin (50 mg/kg) at the gene, protein and histopathological level. Conclusion Low-and medium-dose amygdalin did not induce toxicity in the hepatic and testicular tissues of male mice, unlike high-dose amygdalin, which had a negative effect on oxidative balance in mice. Therefore, amygdalin at a moderate dose may improve oxidative balance in mice.

scholarly journals Systematic evaluation of CdSe/ZnS quantum dots toxicity on the reproduction and offspring health in male BALB/c mice

2021 ◽  
Vol 211 ◽  
pp. 111946
Author(s):  
Li Li ◽  
Xiaotan Lin ◽  
Tingting Chen ◽  
Kan Liu ◽  
Yajing Chen ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Systematic Evaluation ◽  
Offspring Health

Abstract 76: Ablation of Parkin Attenuates Acute Cardiotoxicity of Doxorubicin Associated with Mitophagy

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Chengqun Huang ◽  
Allen Andres ◽  
Jennifer Ramil ◽  
Roberta Gottlieb
Keyword(s):  
Body Weight ◽  
Cardiac Dysfunction ◽  
Mitochondrial Protein ◽  
Significant Loss ◽  
High Dose ◽  
Male Mice ◽  
Mitochondrial Content ◽  
Significant Deterioration ◽  
Knock Out ◽  
Acute Cardiotoxicity

Parkin is an E3 ubiquitin ligase expressed in heart, skeletal muscle and brain. However, the function of Parkin in the heart is largely unknown. We previously showed in cardiomyocytes and the ischemic heart that Parkin translocates to mitochondria to selectively remove damaged mitochondria through autophagy. It has been shown that Doxorubicin (Dox) induces cardiotoxicity characterized by impaired mitochondrial respiration and energetic failure (PLoS One. 2010; 5:e12733). Here, we investigated the role of Parkin in acute Doxorubicin-induced cardiac dysfunction in mice. Acute cardiotoxicity was induced by IP injection of a single dose of 15 mg/kg Doxorubicin hydrochloride in 10-12 wk-old C57BL/6J (WT) mice and Parkin knock out (PKO) mice matched by age, sex and body weight. Analysis of histology, hemodynamics, and mitochondrial content was performed 7d after Dox. Dox induced significant loss of body weight but less in PKO mice (20% in WT vs 12% in PKO). Dox toxicity was more severe in male mice. Signs of discomfort (decreased mobility and hunched posture) were noted 4d after Dox in 90% of WT male mice vs. 20% of PKO males. Mortality at 7d was 30% in WT mice vs. 10% in PKO mice. Dox caused reduction in heart size to a greater extent (10-20%) in WT than in PKO mice. Significant deterioration of hemodynamics was seen in WT mice 7d after Dox; this was attenuated in PKO mice. Because Parkin mediates mitophagy, we examined autophagy and mitochondrial content 7d in Dox treated hearts. Dox resulted in extensive autophagy and decreased mitochondrial protein content in WT mice; this was attenuated in PKO mice. These results suggest that high-dose Dox triggers extensive Parkin-dependent mitophagy which may contribute to acute cardiac dysfunction. We suggest that therapy directed at the PINK1-Parkin mitophagy pathway may be beneficial in the setting of doxorubicin overdose.

scholarly journals Combining a High Dose of Metformin With the SIRT1 Activator, SRT1720, Reduces Life Span in Aged Mice Fed a High-Fat Diet

2020 ◽  
Vol 75 (11) ◽  
pp. 2037-2041 ◽  
Author(s):  
Dushani L Palliyaguru ◽  
Robin K Minor ◽  
Sarah J Mitchell ◽  
Hector H Palacios ◽  
Jordan J Licata ◽  
...  
Keyword(s):  
Body Weight ◽  
Life Span ◽  
High Fat Diet ◽  
High Dose ◽  
Male Mice ◽  
High Fat ◽  
Sharp Reduction ◽  
Antidiabetic Drug ◽  
Older Populations ◽  
Sirt1 Activator

Abstract SRT1720, a sirtuin1-activator, and metformin (MET), an antidiabetic drug, confer health and life-span benefits when administered individually. It is unclear whether combination of the two compounds could lead to additional benefits. Groups of 56-week-old C57BL/6J male mice were fed a high-fat diet (HFD) alone or supplemented with either SRT1720 (2 g/kg food), a high dose of MET (1% wt/wt food), or a combination of both. Animals were monitored for survival, body weight, food consumption, body composition, and rotarod performance. Mice treated with MET alone did not have improved longevity, and life span was dramatically reduced by combination of MET with SRT1720. Although all groups of animals were consuming similar amounts of food, mice on MET or MET + SRT1720 showed a sharp reduction in body weight. SRT1720 + MET mice also had lower percent body fat combined with better performance on the rotarod compared to controls. These data suggest that co-treatment of SRT1720 with MET is detrimental to survival at the doses used and, therefore, risk-benefits of combining life-span-extending drugs especially in older populations needs to be systematically evaluated.

Oncogenicity Study of Acrolein in Mice

1991 ◽  
Vol 10 (6) ◽  
pp. 647-659 ◽  
Author(s):  
Richard A. Parent ◽  
Halina E. Caravello ◽  
James E. Long
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Dose Level ◽  
Body Weight Gain ◽  
High Dose ◽  
Male Mice ◽  
High Dose Level ◽  
Oral Intubation ◽  
Blood Smears ◽  
Dose Dependent

Five hundred seventy CD-1 mice were divided equally by gender and assigned to three groups of 70 per gender and one group of 75 per gender. The first three groups were dosed via oral intubation at 0, 0.5, and 2.0 mg/kg/day while the larger groups were dosed at 4.5 mg/kg/day. Observations were made twice daily and blood smears taken at 12 and 18 months. All animals were sacrificed at 18 months; organs were weighed and examined grossly and microscopically. Treated animals showed decreased body weight gain and male mice demonstrated increased mortality, particularly at the high-dose level. Gross and microscopic lesions were not obviously dose dependent. In this study, acrolein was not shown to have oncogenic properties.

Restraint stress of male mice triggers apoptosis in spermatozoa and spermatogenic cells via activating the TNF-α system

Zygote ◽  
2020 ◽  
Vol 28 (2) ◽  
pp. 160-169 ◽  
Author(s):  
Jie Zhang ◽  
De-Ling Kong ◽  
Bin Xiao ◽  
Hong-Jie Yuan ◽  
Qiao-Qiao Kong ◽  
...  
Keyword(s):  
Psychological Stress ◽  
Restraint Stress ◽  
Semen Quality ◽  
Sperm Quality ◽  
Fertilization Rate ◽  
Seminiferous Tubules ◽  
Spermatogenic Cells ◽  
Male Mice ◽  
Testicular Cells ◽  
Tnf Α

SummaryStudies have indicated that psychological stress impairs human fertility and that various stressors can induce apoptosis of testicular cells. However, the mechanisms by which psychological stress on males reduces semen quality and stressors induce apoptosis in testicular cells are largely unclear. Using a psychological (restraint) stress mouse model, we tested whether male psychological stress triggers apoptosis of spermatozoa and spermatogenic cells through activating tumour necrosis factor (TNF)-α signalling. Wild-type or TNF-α−/− male mice were restrained for 48 h before examination for apoptosis and expression of TNF-α and TNF receptor 1 (TNFR1) in spermatozoa, epididymis, seminiferous tubules and spermatogenic cells. The results showed that male restraint significantly decreased fertilization rate and mitochondrial membrane potential, while increasing levels of malondialdehyde, active caspase-3, TNF-α and TNFR1 in spermatozoa. Male restraint also increased apoptosis and expression of TNF-α and TNFR1 in caudae epididymides, seminiferous tubules and spermatogenic cells. Sperm quality was also significantly impaired when spermatozoa were recovered 35 days after male restraint. The restraint-induced damage to spermatozoa, epididymis and seminiferous tubules was significantly ameliorated in TNF-α−/− mice. Furthermore, incubation with soluble TNF-α significantly reduced sperm motility and fertilizing potential. Taken together, the results demonstrated that male psychological stress induces apoptosis in spermatozoa and spermatogenic cells through activating the TNF-α system and that the stress-induced apoptosis in spermatogenic cells can be translated into impaired quality in future spermatozoa.

Relapse After Early-Stage, Favorable Hodgkin Lymphoma: Disease Characteristics and Outcomes With Conventional or High-Dose Chemotherapy

2021 ◽  
Vol 39 (2) ◽  
pp. 107-115
Author(s):  
Paul J. Bröckelmann ◽  
Horst Müller ◽  
Teresa Guhl ◽  
Karolin Behringer ◽  
Michael Fuchs ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
High Dose Chemotherapy ◽  
Sensitivity Analyses ◽  
High Dose ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Significant Difference ◽  
First Diagnosis

PURPOSE We evaluated disease and treatment characteristics of patients with relapse after risk-adapted first-line treatment of early-stage, favorable, classic Hodgkin lymphoma (ES-HL). We compared second-line therapy with high-dose chemotherapy and autologous stem cell transplantation (ASCT) or conventional chemotherapy (CTx). METHODS We analyzed patients with relapse after ES-HL treated within the German Hodgkin Study Group HD10+HD13 trials. We compared, by Cox proportional hazards regression, progression-free survival (PFS) after relapse (second PFS) treated with either ASCT or CTx and performed sensitivity analyses with overall survival (OS) from relapse and Kaplan-Meier statistics. RESULTS A total of 174 patients’ disease relapsed after treatment in the HD10 (n = 53) and HD13 (n = 121) trials. Relapse mostly occurred > 12 months after first diagnosis, predominantly with stage I-II disease. Of 172 patients with known second-line therapy, 85 received CTx (49%); 70, ASCT (41%); 11, radiotherapy only (6%); and 4, palliative single agent therapies (2%). CTx was predominantly bleomycin, etoposide, doxorubicin cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP [68%]), followed by the combination regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (19%), or other regimens (13%). Patients aged > 60 years at relapse had shorter second PFS (hazard ratio [HR], 3.0; P = .0029) and were mostly treated with CTx (n = 33 of 49; 67%) and rarely with ASCT (n = 8; 16%). After adjustment for age and a disadvantage of ASCT after the more historic HD10 trial, we did not observe a significant difference in the efficacy of CTx versus ASCT for second PFS (HR, 0.7; 95% CI, 0.3 to 1.6; P = .39). In patients in the HD13 trial who were aged ≤ 60 years, the 2-year, second PFS rate was 94.0% with CTx (95% CI, 85.7% to 100%) versus 83.3% with ASCT (95% CI, 71.8% to 94.8%). Additional sensitivity analyses including OS confirmed these observations. CONCLUSION After contemporary treatment of ES-HL, relapse mostly occurred > 12 months after first diagnosis. Polychemotherapy regimens such as BEACOPP are frequently administered and may constitute a reasonable treatment option for selected patients with relapse after ES-HL.

scholarly journals Palmitoylethanolamide: Prenatal Developmental Toxicity Study in Rats

2021 ◽  
pp. 109158182098607
Author(s):  
Narendra S. Deshmukh ◽  
Shailesh Gumaste ◽  
Silma Subah ◽  
Nathasha Omal Bogoda
Keyword(s):  
Body Weight ◽  
Developmental Toxicity ◽  
Reproductive Toxicity ◽  
Toxicity Study ◽  
High Dose ◽  
Pregnant Rats ◽  
Human Dose ◽  
Adverse Effect Level ◽  
Female Wistar Rats ◽  
Effect Level

Palmitoylethanolamide (PEA) is an endogenous ethanolamine playing a protective and homeodynamic role in animals and plants. Prenatal developmental toxicity of PEA was tested following oral administration to pregnant female Wistar rats, from days 0 to 19 of gestation, at dosage of 250, 500, or 1,000 mg/kg body weight, according to Organisation for Economic Co-operation and Development Test Guideline No. 414. On gestation day 20, cesarean sections were performed on the dams, followed by examination of their ovaries and uterine contents. The fetuses were further examined for external, visceral, and skeletal abnormalities. Palmitoylethanolamide did not cause any alterations at any of the given dosages in the measured maternal parameters of systemic toxicity (body weight, food consumption, survival, thyroid functions, organ weight, histopathology), reproductive toxicity (preimplantation and postimplantation losses, uterus weight, number of live/dead implants and early/late resorptions, litter size and weights, number of fetuses, their sex ratio), and fetal external, visceral, or skeletal observations. Any alterations that were recorded were “normal variations” or “minor anomalies,” which were unrelated to treatment with PEA. Under the condition of this prenatal study, the no-observed-adverse-effect level of PEA for maternal toxicity, embryotoxicity, fetotoxicity, and teratogenicity in rats was found to be >1,000 mg/kg body weight/d. It indicates that PEA is well tolerated by and is safe to pregnant rats even at a high dose of 1,000 mg/kg body weight/d, equivalent to a human dose of greater than 9.7 g/d. This prenatal developmental toxicity study contributes greatly in building a robust safety profile for PEA.

scholarly journals Adjuvant brachytherapy for FIGO stage I serous or clear cell endometrial cancer

2021 ◽  
pp. ijgc-2020-002217
Author(s):  
Elizabeth B Jeans ◽  
William G Breen ◽  
Trey C Mullikin ◽  
Brittany A Looker ◽  
Andrea Mariani ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Clear Cell ◽  
Early Stage ◽  
Figo Stage ◽  
Stage I ◽  
High Dose ◽  
Vaginal Cuff ◽  
Locoregional Failure ◽  
Platinum Based Chemotherapy ◽  
Increased Risk

ObjectivesOptimal adjuvant treatment for early-stage clear cell and serous endometrial cancer remains unclear. We report outcomes for women with surgically staged International Federation of Gynecology and Obstetrics (FIGO) stage I clear cell, serous, and mixed endometrial cancers following adjuvant vaginal cuff brachytherapy with or without chemotherapy.MethodsFrom April 1998 to January 2020, women with FIGO stage IA–IB clear cell, serous, and mixed endometrial cancer underwent surgery and adjuvant vaginal cuff brachytherapy. Seventy-six patients received chemotherapy. High-dose rate vaginal cuff brachytherapy was planned to a total dose of 21 gray in three fractions using a multichannel vaginal cylinder. The primary objective was to determine the effectiveness of adjuvant vaginal cuff brachytherapy and to identify surgicopathological risk factors that could portend towards worse oncological outcomes.ResultsA total of 182 patients were included in the analysis. Median follow-up was 5.3 years (2.3–12.2). Ten-year survival was 73.3%. Five-year cumulative incidence (CI) of vaginal, pelvic, and para-aortic relapse was 1.4%, 2.1%, and 0.9%, respectively. Five-year locoregional failure, any recurrence, peritoneal relapse, and other distant recurrence was 4.4%, 11.6%, 5.3%, and 6.7%, respectively. On univariate analysis, locoregional failure was worse for larger tumors (per 1 cm) (HR 1.9, 95% CI 1.2 to 3.0, p≤0.01). Any recurrence was worse for tumors of at least 3.5 cm (HR 3.8, 95% CI 1.3 to 11.7, p=0.02) and patients with positive/suspicious cytology (HR 4.4, 95% CI 1.5 to 12.4, p≤0.01). Ten-year survival for tumors of at least 3.5 cm was 56.9% versus 86.6% for those with smaller tumors (HR 2.9, 95% CI 1.4 to 5.8, p≤0.01). Ten-year survival for positive/suspicious cytology was 50.9% versus 77.4% (HR 2.2, 95% CI 0.9 to 5.4, p=0.09). Multivariate modeling demonstrated worse locoregional failure, any recurrence, and survival with larger tumors, as well as any recurrence with positive/suspicious cytology. Subgroup analysis demonstrated improved outcomes with the use of adjuvant chemotherapy in patients with large tumors or positive/suspicious cytology.ConclusionAdjuvant vaginal cuff brachytherapy alone without chemotherapy is an appropriate treatment for women with negative peritoneal cytology and small, early-stage clear cell, serous, and mixed endometrial cancer. Larger tumors or positive/suspicious cytology are at increased risk for relapse and worse survival, and should be considered for additional upfront adjuvant treatments, such as platinum-based chemotherapy.

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