Dose-Dependent Effect of Polystyrene Microplastics on the Testicular Tissues of the Male Sprague Dawley Rats.
Ontology highlight
ABSTRACT:
SUBMITTER: Ijaz MU
PROVIDER: S-EPMC8182192 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Silver nanoparticles are known to be distributed in many tissues after oral or inhalation exposure. Thus, understanding the tissue clearance of such distributed nanoparticles is very important to understand the behavior of silver nanoparticles in vivo. For risk assessment purposes, easy clearance indicates a lower overall cumulative toxicity. Accordingly, to investigate the clearance of tissue silver concentrations following oral silver nanoparticle exposure, Sprague-Dawley rats were assigned to 3 groups: control, low dose (100 mg/kg body weight), and high dose (500 mg/kg body weight), and exposed to two different sizes of silver nanoparticles (average diameter 10 and 25 nm) over 28 days. Thereafter, the rats were allowed to recover for 4 months. Regardless of the silver nanoparticle size, the silver content in most tissues gradually decreased during the 4-month recovery period, indicating tissue clearance of the accumulated silver. The exceptions were the silver concentrations in the brain and testes, which did not clear well, even after the 4-month recovery period, indicating an obstruction in transporting the accumulated silver out of these tissues. Therefore, the results showed that the size of the silver nanoparticles did not affect their tissue distribution. Furthermore, biological barriers, such as the blood-brain barrier and blood-testis barrier, seemed to play an important role in the silver clearance from these tissues.
| S-EPMC3734196 | biostudies-literature
Project description:OBJECTIVES: The aims of the study were to test the single-dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP) in Sprague-Dawley (SD) rats and to estimate the crude lethal dose. METHODS: The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP) laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156). The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group). General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA) by using statistical analysis system (SAS, version 9.2). RESULTS: No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. CONCLUSION: Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg.
| S-EPMC4481398 | biostudies-literature
Project description:ObjectiveFluorophore-labeled contrast imaging agents are moving toward clinical use for a number of applications. The near-infrared dye IRDye 800CW is frequently used in its N-hydroxysuccinamide (NHS) ester form for labeling these agents. Following conjugation or breakdown of a labeled ligand, excess NHS ester is converted to the carboxylate form. To prepare for clinical use as a near-infrared fluorophore, a toxicity study was conducted on IRDye 800CW carboxylate.MethodsMale and female Sprague-Dawley rats were given a single intravenous or intradermal administration of IRDye 800CW carboxylate; Indocyanine Green was used as a comparative control. Animals were injected with varying doses of the test and control articles and observed for up to 14 days. Clinical chemistry, hematological, and pharmacokinetic analyses were performed on subgroups of animals. Organs were analyzed for content of the test article. Tissues were analyzed microscopically for pathological changes.ResultsBased on hematologic, clinical chemistry, and histopathologic evaluation, single administration of IRDye 800CW carboxylate intravenously at dose levels of 1, 5, and 20 mg/kg or 20 mg/kg intradermally produced no pathological evidence of toxicity.ConclusionA dose of 20 mg/kg was identified as the no observed adverse effect level following IV or ID routes of administration of IRDye 800CW.
| S-EPMC2978892 | biostudies-literature
Project description:Proton radiotherapy causes less off-target effects than X-rays but is not without effect. To reduce adverse effects of proton radiotherapy, a model of cognitive deficits from conventional proton exposure is needed. We developed a model emphasizing multiple cognitive outcomes. Adult male rats (10/group) received a single dose of 0, 11, 14, 17, or 20 Gy irradiation (the 20 Gy group was not used because 50% died). Rats were tested once/week for 5 weeks post-irradiation for activity, coordination, and startle. Cognitive assessment began 6-weeks post-irradiation with novel object recognition (NOR), egocentric learning, allocentric learning, reference memory, and proximal cue learning. Proton exposure had the largest effect on activity and prepulse inhibition of startle 1-week post-irradiation that dissipated each week. 6-weeks post-irradiation, there were no effects on NOR, however proton exposure impaired egocentric (Cincinnati water maze) and allocentric learning and caused reference memory deficits (Morris water maze), but did not affect proximal cue learning or swimming performance. Proton groups also had reduced striatal levels of the dopamine transporter, tyrosine hydroxylase, and the dopamine receptor D1, effects consistent with egocentric learning deficits. This new model will facilitate investigations of different proton dose rates and drugs to ameliorate the cognitive sequelae of proton radiotherapy.
| S-EPMC7726106 | biostudies-literature
Project description:BACKGROUND:3,4-methylenedioxypyrovalerone (MDPV) toxicity includes intense neurological and cardiovascular events. We examined MDPV-induced cardiovascular, temperature, and locomotor effects following escalating and repeated MDPV administration in adult male and female Sprague-Dawley rats and compared these effects to cocaine in male rats. METHODS:Telemetry devices were surgically implanted to allow continuous measurement of cardiovascular, temperature, and locomotor activity over a 22?h period after dosing. Rats were administered increasing intraperitoneal (IP) MDPV doses (1-5.6?mg/kg) every other day, followed two days later by a binge regimen of four injections of 3?mg/kg MDPV at 2?h intervals. MDPV serum concentrations were measured by LC-MS/MS. Cocaine (3-30?mg/kg) and four injections of 30?mg/kg IP were administered to male rats for comparison with male MDPV data. RESULTS:The duration of MDPV cardiovascular effects was significantly greater (p?<?0.05) in male rats than female rats at 3-5.6?mg/kg. The ED50 for MDPV-induced locomotor was significantly lower in males (2.4?±?0.3) than females (3.4?±?0.2). Males showed significantly greater variability in MDPV serum concentrations than females after binge dosing. MDPV produced five-fold more potent cardiovascular effects than cocaine in male rats. MDPV did not alter thermoregulation in either sex, but cocaine binge administration decreased temperature. CONCLUSION:Effects of MDPV on temperature were not significantly different between sexes. MDPV-induced cardiovascular and locomotor effects in males lasted significantly longer and were more potent than in females. These differences appeared to be related to pharmacokinetic factors leading to greater variance in MDPV serum concentrations in males.
| S-EPMC6915966 | biostudies-literature
Project description:3,3',4,4',5-Pentachlorobiphenyl (PCB 126), an aryl hydrocarbon receptor (AhR) agonist and most potent dioxin-like PCB congener, significantly alters gene expression, lipid metabolism, and oxidative stress in the liver. PON1, an antioxidant and anti-atherogenic enzyme, is produced in the liver and secreted into the blood where it is incorporated into high density lipoprotein (HDL) and protects LDL and cellular membranes against lipid peroxidation. To explore the regulation of PON1, male Sprague-Dawley rats were treated with ip injections of corn oil or 1 ?mol/kg or 5 ?mol/kg PCB 126 and euthanized up to two weeks afterwards. Serum total and HDL-cholesterol were increased by low dose and decreased by high dose exposure, while LDL-cholesterol was unchanged. PCB 126 significantly increased hepatic PON1 gene expression and liver and serum PON1 activities. Liver and serum thiobarbituric acid reactive substances levels were not elevated except for high dose and long exposure times. Serum antioxidant capacity was unchanged across all exposure doses and time points. This study, the first describing the regulation of gene expression of PON1 by a PCB congener, raises interesting questions whether elevated PON1 is able to ameliorate PCB 126-induced lipid peroxidation and whether serum PON1 levels may serve as a new biomarker of exposure to dioxin-like compounds.
| S-EPMC3288253 | biostudies-literature
Project description:PurposePortal vein embolization (PVE) is an established neoadjuvant method to induce future liver remnant hypertrophy prior to surgical resection of hepatic tumors. The purpose of our study was to examine the feasibility of PVE with glass 90Y microspheres (Y90 PVE) in Sprague-Dawley rats. We tested the hypothesis that increased doses of Y90 PVE would increase target lobe fibrosis and atrophy.MethodsTwenty-two rats were assigned to four groups for Y90 PVE to the right median lobe: very high- (273.8 MBq; n = 2), high- (99.9 MBq; n = 10), medium- (48.1 MBq; n = 5), and low-dose (14.8 MBq; n = 5). An untreated control group included seven rats. 90Y PET/CT of 90Y distributions confirmed lobar targeting. MRI volumes were measured at baseline, 2-, 4-, 8- and 12-weeks. Explanted hepatic lobes were weighed, sectioned, and stained for H&E and immunohistochemistry. Digitized slides allowed quantitative measurements of fibrosis (20 foci/slide).ResultsEx vivo measurements confirmed 91-97% activity was localized to the target lobe (n = 4). The percent growth of the target lobe relative to baseline was - 5.0% (95% CI - 17.0-6.9%) for high-, medium dose rats compared to + 18.6% (95% CI + 7.6-29.7%) in the low-dose group at 12-weeks (p = 0.0043). Radiation fibrosis increased in a dose-dependent fashion. Fibrotic area/microsphere was 22,893.5, 14,946.2 ± 2253.3, 15,304.5 ± 4716.6, and 5268.8 ± 2297.2 μm2 for very high- (n = 1), high- (n = 4), medium- (n = 3), and low-dose groups (n = 5), respectively.ConclusionY90 PVE was feasible in the rat model, resulted in target lobe atrophy, and dose-dependent increases in hepatic fibrosis at 12 weeks. The onset of imaging-based volumetric changes was 8-12 weeks.
| S-EPMC7655630 | biostudies-literature
Project description:Lung transcriptome sequencing anlysis in LPS-induced ALI model rats (Male Sprague-Dawley rats) after treatment with Ma Xing Shi Gan Decoction, In summary, our study suggests that MXSG inhibits viral invasion, proliferation, and mitigation of virus-induced lung injury, which may be a key mechanism of its therapeutic effect on COVID-19. These results provide experience for the treatment of infectious diseases and lung injury. we dissected the chemical components of MXSG by liquid chromatography-mass spectrometry (LC-ESI-MS/MS) and analyzed the intervention pathways of MXSG based on components detected through network pharmacology. At the same time, the therapeutic effect of MXSG on COVID-19 was explained through published articles, and the relevant regulatory mechanism was proposed. Then, in this study, the regulatory effect of MXSG on inflammatory lung injury was explorated through transcriptome results.
2020-10-01 | GSE158832 | GEO
Project description:BackgroundInvestigations into the mechanism of diffuse retinal edema in diabetic subjects have been limited by a lack of animal models and techniques that co-localized retinal thickness and hydration in vivo. In this study we test the hypothesis that a previously reported supernormal central retinal thickness on MRI measured in experimental diabetic retinopathy in vivo represents a persistent and diffuse edema.Methodology/principal findingsIn diabetic and age-matched control rats, and in rats experiencing dilutional hyponatremia (as a positive edema control), whole central retinal thickness, intraretinal water content and apparent diffusion coefficients (ADC, 'water mobility') were measured in vivo using quantitative MRI methods. Glycated hemoglobin and retinal thickness ex vivo (histology) were also measured in control and diabetic groups. In the dilutional hyponatremia model, central retinal thickness and water content were supernormal by quantitative MRI, and intraretinal water mobility profiles changed in a manner consistent with intracellular edema. Groups of diabetic (2, 3, 4, 6, and 9 mo of diabetes), and age-matched controls were then investigated with MRI and all diabetic rats showed supernormal whole central retinal thickness. In a separate study in 4 mo diabetic rats (and controls), MRI retinal thickness and water content metrics were significantly greater than normal, and ADC was subnormal in the outer retina; the increase in retinal thickness was not detected histologically on sections of fixed and dehydrated retinas from these rats.Conclusions/significanceDiabetic male Sprague Dawley rats demonstrate a persistent and diffuse retinal edema in vivo, providing, for the first time, an important model for investigating its pathogenesis and treatment. These studies also validate MRI as a powerful approach for investigating mechanisms of diabetic retinal edema in future experimental and clinical investigations.
| S-EPMC3256169 | biostudies-literature
Project description:BackgroundPlastic pollution is greatly serious in the ocean and soil. Microplastics (MPs) degraded from plastic has threatened animals and humans health. The accumulation of MPs in the tissues and blood in animals and humans has been found. There is therefore a need to assess the toxicological effects of MPs on the reproductive system.ResultsIn this study, we explored the effect of polystyrene microplastics (PS-MPs) on premature testicular aging in vitro and in vivo. In vitro, we found that testicular sertoli cells (TM4 cells) was prematurely senescent following PS-MPs treatment by the evaluation of a range of aging marker molecules (such as Sa-β-gal, p16 and 21). TM4 cells were then employed for in vitro model to study the potential molecular mechanism by which PS-MPs induce the premature senescence of TM4 cells. NF-κB is identified as a key molecule for PS-MPs-induced TM4 cellular senescence. Furthermore, through eliminating reactive oxygen species (ROS), the activation of nuclear factor kappa B (NF-κB) was blocked in PS-MPs-induced senescent TM4 cells, indicating that ROS triggers NF-κB activation. Next, we analyzed the causes of mitochondrial ROS (mtROS) accumulation induced by PS-MPs, and results showed that Ca2+ overload induced the accumulation of mtROS. Further, PS-MPs exposure inhibits mitophagy, leading to the continuous accumulation of senescent cells. In vivo, 8-week-old C57 mice were used as models to assess the effect of PS-MPs on premature testicular aging. The results illustrated that PS-MPs exposure causes premature aging of testicular tissue by testing aging markers. Additionally, PS-MPs led to oxidative stress and inflammatory response in the testicular tissue.ConclusionIn short, our experimental results revealed that PS-MPs-caused testicular premature aging is dependent on Ca2+/ROS/NF-κB signaling axis. The current study lays the foundation for further exploration of the effects of microplastics on testicular toxicology.
| S-EPMC10463354 | biostudies-literature