Evaluation of Resmethrin Toxicity to Neonatal Testes in Organ Culture

2019 ◽  
Vol 173 (1) ◽  
pp. 53-64 ◽  
Author(s):  
Hyun-Jung Park ◽  
Won-Young Lee ◽  
Mingtian Zhang ◽  
Kwon-Ho Hong ◽  
Chankyu Park ◽  
...  
Keyword(s):  
Organ Culture ◽  
Germ Cells ◽  
Methodological Approach ◽  
Reproductive Toxicity ◽  
Laboratory Animals ◽  
Marker Genes ◽  
Low Toxicity ◽  
Apoptotic Effects

Abstract Resmethrin is a widely used pyrethroid insecticide, which causes low toxicity in mammals. However, its toxicity in testes has not been fully investigated. Therefore, we evaluated the toxicity of resmethrin in mouse testes using an in vitro organ culture. Mouse testicular fragments (MTFs) derived from neonates were cultured in medium containing resmethrin for 30 days. Effects on spermatogenesis in the cultured testes were investigated as functions of both time and dose. Resmethrin significantly downregulated the transcription levels of marker genes for spermatogonia and the number of spermatogenic germ cells relative to those of the controls, according to quantitative PCR and immunostaining. In addition, spermatocyte was observed in the control, but not in 50 μM resmethrin-exposed cultures. Levels of the SYCP3 meiotic marker and phosphorylated H2AX decreased by resmethrin treatment, as observed by Western blotting. Toxic or apoptotic effects of resmethrin in Sertoli and Leydig cells from MTFs were not observed by immunostaining and Tunnel assay. No changes in the expression of steroidogenic enzymes were noted. Apoptosis was only detected in the germ cells of resmethrin-treated MTFs. Thus, the highest dose of resmethrin tested (50 μM) completely inhibited spermatogenesis, because of apoptosis of germ cells and spermatocytes. Although the in vivo toxicity of resmethrin has not yet been studied in detail, significant evidence for cytotoxicity was observed in our organ cultures. This methodological approach is useful for the study of reproductive toxicity before proceeding to animal models, as it greatly reduces the use of laboratory animals.

scholarly journals ASSESSING RISKS CAUSED BY NICKEL-CONTAINING NANOMATERIALS: HAZARD CHARACTERIZATION IN VIVO

2021 ◽  
pp. 177-191
Author(s):  
I.V. Gmoshinski ◽  
◽  
S.A. Khotimchenko ◽  
◽  
Keyword(s):  
Human Health Risk ◽  
Reproductive Toxicity ◽  
Construction Materials ◽  
Toxic Effects ◽  
Laboratory Animals ◽  
Hazard Characterization ◽  
Carcinogenic Potential ◽  
Transforma Tion

Nanoparticles (NP) of nickel (Ni) and its compounds are promising materials for being used as catalysts in chemical, pharmaceutical and food industry; as construction materials in electronics and optoelectronics, in manufacturing current sources, medications, diagnostic preparations, and pesticides. Annual production volumes for these materials in their nano- form are equal to dozen tons and are expected to growth further. According to data obtained via multiple research nano- forms of Ni and its compounds are toxic to many types of cells; stimulate apoptosis; and can induce malignant transforma- tion in vitro. It indicates that this group of nanomaterials can possibly be hazardous for human health. Risk assessment in- cludes such a necessary stage as quantitative hazard characterization, that is, establishing toxic and maximum no-observed- adverse-effect levels (NOAEL) for a nanomaterial that penetrates into a body via inhalation, through undamaged skin, or the gastrointestinal tract. Experiments in vivo performed on laboratory animals with Ni-containing materials revealed overall toxic effects; toxicity to specific organs (including hepatoxoticity and cardiotoxicity); atherogenic, allergenic, and immune- toxic effects, as well as reproductive toxicity. There are multiple available data indicating that all Ni-containing nanomate- rials are genotoxic and mutagenic, though data on their carcinogenic potential are rather scarce. Factors that determine toxicity of Ni and its compounds in nanoform are their ability to penetrate through biological barriers and to release free Ni++ ions in biological media. The review focuses on analyzing and generalizing data on toxicity signs in vivo and effective toxic doses under various introductions of Ni and its compounds in nanoform into a body over a period starting predominantly from 2011.

scholarly journals The Use of the Adaptation Potential Reduction Model for Reproductive Toxicity Research In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Nadezhda V. Tyshko ◽  
Elvira O. Sadykova ◽  
Svetlana I. Shestakova ◽  
Nikolay S. Nikitin ◽  
Marina D. Trebukh ◽  
...  
Keyword(s):  
Reproductive Toxicity ◽  
Reproductive Function ◽  
Laboratory Animals ◽  
Toxic Factor ◽  
Potential Reduction ◽  
Reduction Model ◽  
Adaptation Potential ◽  
Low Toxicity ◽  
Basic Level

The modeling of adaptation potential decrease in rats due to modification of the diet’s vitamin–mineral composition allows to increase animals’ sensitivity to toxic load in reprotoxicological experiments. The threshold values of vitamins B1, B2, B3, and B6 and mineral substances Fe3+ and Mg2+ in the diet, which lead to a considerable reduction of laboratory animals’ adaptation potential, have been determined as 19% (from the basic level in the diet) for males and 18% for females. The efficiency of this model has been confirmed in a reprotoxicological experiment with glyphosate as a toxic factor: the action of the toxic factor against the background of reduced availability of B vitamins and salts Fe3+ and Mg2+ led to significant changes in such indicators of reproductive function as mating efficiency, postimplantation loss, and the total number of alive pups, while the toxic effect of glyphosate was not so pronounced against the normal level of essential substances. The obtained results prove that this adaptation potential reduction model can be recommended for the research of the low-toxicity objects reproductive toxicity in rats and for the safety assessment of novel food, in particular.

scholarly journals ASSESSING RISKS CAUSED BY NICKEL-CONTAINING NANOMATERIALS: HAZARD CHARACTERIZATION IN VIVO

2021 ◽  
pp. 177-191
Author(s):  
I.V. Gmoshinski ◽  
◽  
S.A. Khotimchenko ◽  
Keyword(s):  
Human Health Risk ◽  
Reproductive Toxicity ◽  
Construction Materials ◽  
Toxic Effects ◽  
Laboratory Animals ◽  
Hazard Characterization ◽  
Carcinogenic Potential ◽  
Transforma Tion

Nanoparticles (NP) of nickel (Ni) and its compounds are promising materials for being used as catalysts in chemical, pharmaceutical and food industry; as construction materials in electronics and optoelectronics, in manufacturing current sources, medications, diagnostic preparations, and pesticides. Annual production volumes for these materials in their nano- form are equal to dozen tons and are expected to growth further. According to data obtained via multiple research nano- forms of Ni and its compounds are toxic to many types of cells; stimulate apoptosis; and can induce malignant transforma- tion in vitro. It indicates that this group of nanomaterials can possibly be hazardous for human health. Risk assessment in- cludes such a necessary stage as quantitative hazard characterization, that is, establishing toxic and maximum no-observed- adverse-effect levels (NOAEL) for a nanomaterial that penetrates into a body via inhalation, through undamaged skin, or the gastrointestinal tract. Experiments in vivo performed on laboratory animals with Ni-containing materials revealed overall toxic effects; toxicity to specific organs (including hepatoxoticity and cardiotoxicity); atherogenic, allergenic, and immune- toxic effects, as well as reproductive toxicity. There are multiple available data indicating that all Ni-containing nanomate- rials are genotoxic and mutagenic, though data on their carcinogenic potential are rather scarce. Factors that determine toxicity of Ni and its compounds in nanoform are their ability to penetrate through biological barriers and to release free Ni++ ions in biological media. The review focuses on analyzing and generalizing data on toxicity signs in vivo and effective toxic doses under various introductions of Ni and its compounds in nanoform into a body over a period starting predominantly from 2011.

Neurotoxicity of Pesticides: The Roadmap for the Cubic Mode of Action

2020 ◽  
Vol 27 (1) ◽  
pp. 54-77 ◽  
Author(s):  
Bogdan Bumbăcilă ◽  
Mihai V. Putz
Keyword(s):  
Biological Activity ◽  
Wiener Index ◽  
Laboratory Animals ◽  
Covalent Bonds ◽  
Organophosphate Compounds ◽  
Sar Studies ◽  
Structure Activity ◽  
Cubic Structure

Pesticides are used today on a planetary-wide scale. The rising need for substances with this biological activity due to an increasing consumption of agricultural and animal products and to the development of urban areas makes the chemical industry to constantly investigate new molecules or to improve the physicochemical characteristics, increase the biological activities and improve the toxicity profiles of the already known ones. Molecular databases are increasingly accessible for in vitro and in vivo bioavailability studies. In this context, structure-activity studies, by their in silico - in cerebro methods, are used to precede in vitro and in vivo studies in plants and experimental animals because they can indicate trends by statistical methods or biological activity models expressed as mathematical equations or graphical correlations, so a direction of study can be developed or another can be abandoned, saving financial resources, time and laboratory animals. Following this line of research the present paper reviews the Structure-Activity Relationship (SAR) studies and proposes a correlation between a topological connectivity index and the biological activity or toxicity made as a result of a study performed on 11 molecules of organophosphate compounds, randomly chosen, with a basic structure including a Phosphorus atom double bounded to an Oxygen atom or to a Sulfur one and having three other simple covalent bonds with two alkoxy (-methoxy or -ethoxy) groups and to another functional group different from the alkoxy groups. The molecules were packed on a cubic structure consisting of three adjacent cubes, respecting a principle of topological efficiency, that of occupying a minimal space in that cubic structure, a method that was called the Clef Method. The central topological index selected for correlation was the Wiener index, since it was possible this way to discuss different adjacencies between the nodes in the graphs corresponding to the organophosphate compounds molecules packed on the cubic structure; accordingly, "three dimensional" variants of these connectivity indices could be considered and further used for studying the qualitative-quantitative relationships for the specific molecule-enzyme interaction complexes, including correlation between the Wiener weights (nodal specific contributions to the total Wiener index of the molecular graph) and the biochemical reactivity of some of the atoms. Finally, when passing from SAR to Q(uantitative)-SAR studies, especially by the present advanced method of the cubic molecule (Clef Method) and its good assessment of the (neuro)toxicity of the studied molecules and of their inhibitory effect on the target enzyme - acetylcholinesterase, it can be seen that a predictability of the toxicity and activity of different analogue compounds can be ensured, facilitating the in vivo experiments or improving the usage of pesticides.

scholarly journals Expression Profile of New Marker Genes Involved in Differentiation of Canine Adipose-Derived Stem Cells into Osteoblasts

2021 ◽  
Vol 22 (13) ◽  
pp. 6663
Author(s):  
Maurycy Jankowski ◽  
Mariusz Kaczmarek ◽  
Grzegorz Wąsiatycz ◽  
Claudia Dompe ◽  
Paul Mozdziak ◽  
...  
Keyword(s):  
Stem Cells ◽  
In Vitro Culture ◽  
Osteogenic Differentiation ◽  
Molecular Mechanisms ◽  
Marker Genes ◽  
P Value ◽  
Illumina Platform

Next-generation sequencing (RNAseq) analysis of gene expression changes during the long-term in vitro culture and osteogenic differentiation of ASCs remains to be important, as the analysis provides important clues toward employing stem cells as a therapeutic intervention. In this study, the cells were isolated from adipose tissue obtained during routine surgical procedures and subjected to 14-day in vitro culture and differentiation. The mRNA transcript levels were evaluated using the Illumina platform, resulting in the detection of 19,856 gene transcripts. The most differentially expressed genes (fold change >|2|, adjusted p value < 0.05), between day 1, day 14 and differentiated cell cultures were extracted and subjected to bioinformatical analysis based on the R programming language. The results of this study provide molecular insight into the processes that occur during long-term in vitro culture and osteogenic differentiation of ASCs, allowing the re-evaluation of the roles of some genes in MSC progression towards a range of lineages. The results improve the knowledge of the molecular mechanisms associated with long-term in vitro culture and differentiation of ASCs, as well as providing a point of reference for potential in vivo and clinical studies regarding these cells’ application in regenerative medicine.

scholarly journals Fabrication of 3D-Printed Interpenetrating Hydrogel Scaffolds for Promoting Chondrogenic Differentiation

Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2146
Author(s):  
Jian Guan ◽  
Fu-zhen Yuan ◽  
Zi-mu Mao ◽  
Hai-lin Zhu ◽  
Lin Lin ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Elastic Modulus ◽  
Chondrogenic Differentiation ◽  
Marker Genes ◽  
Self Healing ◽  
Polyethylene Glycol Diacrylate ◽  
3D Microenvironment ◽  
3D Printed

The limited self-healing ability of cartilage necessitates the application of alternative tissue engineering strategies for repairing the damaged tissue and restoring its normal function. Compared to conventional tissue engineering strategies, three-dimensional (3D) printing offers a greater potential for developing tissue-engineered scaffolds. Herein, we prepared a novel photocrosslinked printable cartilage ink comprising of polyethylene glycol diacrylate (PEGDA), gelatin methacryloyl (GelMA), and chondroitin sulfate methacrylate (CSMA). The PEGDA-GelMA-CSMA scaffolds possessed favorable compressive elastic modulus and degradation rate. In vitro experiments showed good adhesion, proliferation, and F-actin and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the scaffolds. When the CSMA concentration was increased, the compressive elastic modulus, GAG production, and expression of F-actin and cartilage-specific genes (COL2, ACAN, SOX9, PRG4) were significantly improved while the osteogenic marker genes of COL1 and ALP were decreased. The findings of the study indicate that the 3D-printed PEGDA-GelMA-CSMA scaffolds possessed not only adequate mechanical strength but also maintained a suitable 3D microenvironment for differentiation, proliferation, and extracellular matrix production of BMSCs, which suggested this customizable 3D-printed PEGDA-GelMA-CSMA scaffold may have great potential for cartilage repair and regeneration in vivo.

scholarly journals Construction of hollow polydopamine nanoparticle based drug sustainable release system and its application in bone regeneration

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Lu Wang ◽  
Shuwei Liu ◽  
Chunxia Ren ◽  
Siyuan Xiang ◽  
Daowei Li ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Load Capacity ◽  
Good Prospect ◽  
Alizarin Red ◽  
Drug Load ◽  
Load Rate ◽  
Low Toxicity

AbstractNanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.

scholarly journals Targeting a Lipid Desaturation Enzyme, SCD1, Selectively Eliminates Colon Cancer Stem Cells through the Suppression of Wnt and NOTCH Signaling

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 106
Author(s):  
Yeongji Yu ◽  
Hyejin Kim ◽  
SeokGyeong Choi ◽  
JinSuh Yu ◽  
Joo Yeon Lee ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Notch Signaling ◽  
Cultured Cells ◽  
Pcr Analysis ◽  
Marker Genes ◽  
Dependent Manner ◽  
Lipid Desaturation ◽  
Novel Target

The elimination of the cancer stem cell (CSC) population may be required to achieve better outcomes of cancer therapy. We evaluated stearoyl-CoA desaturase 1 (SCD1) as a novel target for CSC-selective elimination in colon cancer. CSCs expressed more SCD1 than bulk cultured cells (BCCs), and blocking SCD1 expression or function revealed an essential role for SCD1 in the survival of CSCs, but not BCCs. The CSC potential selectively decreased after treatment with the SCD1 inhibitor in vitro and in vivo. The CSC-selective suppression was mediated through the induction of apoptosis. The mechanism leading to selective CSC death was investigated by performing a quantitative RT-PCR analysis of 14 CSC-specific signaling and marker genes after 24 and 48 h of treatment with two concentrations of an inhibitor. The decrease in the expression of Notch1 and AXIN2 preceded changes in the expression of all other genes, at 24 h of treatment in a dose-dependent manner, followed by the downregulation of most Wnt- and NOTCH-signaling genes. Collectively, we showed that not only Wnt but also NOTCH signaling is a primary target of suppression by SCD1 inhibition in CSCs, suggesting the possibility of targeting SCD1 against colon cancer in clinical settings.

scholarly journals HLA-DR Alpha 2 Mediates Negative Signalling via Binding to Tirc7 Leading to Anti-Inflammatory and Apoptotic Effects in Lymphocytes In Vitro and In Vivo

PLoS ONE ◽  
2008 ◽  
Vol 3 (2) ◽  
pp. e1576 ◽  
Author(s):  
Grit-Carsta Bulwin ◽  
Stephanie Wälter ◽  
Mirko Schlawinsky ◽  
Thomas Heinemann ◽  
Anke Schulze ◽  
...  
Keyword(s):  
Hla Dr ◽  
Anti Inflammatory ◽  
Apoptotic Effects

Pharmacokinetic and toxicology assessment of INTERCEPT (S-59 and UVA treated) platelets

2001 ◽  
Vol 20 (10) ◽  
pp. 533-550 ◽  
Author(s):  
V Ciaravino ◽  
T McCullough ◽  
A D Dayan
Keyword(s):  
Ex Vivo ◽  
Reproductive Toxicity ◽  
In Vivo Studies ◽  
Pathogen Inactivation ◽  
Platelet Concentrates ◽  
Baxter Healthcare ◽  
Safety Margins ◽  
Toxicology Assessment

The pathogen inactivation process developed by Cerus and Baxter Healthcare Corporations uses the psoralen, S-59 (amotosalen) in an ex vivo photochemical treatment (PCT) process to inactivate viruses, bacteria, protozoans, and leukocytes in platelet concentrates and plasma. Studies were performed by intravenous infusion of S-59 PCT formulations-compound adsorption device (CAD) treatment and with non-UVA illuminated S-59, using doses that were multiples of potential clinical exposures. The studies comprised full pharmacokinetic, single and repeated-dose (up to 13 weeks duration) toxicity, safety pharmacology (CNS, renal, and cardiovascular), reproductive toxicity, genotoxicity, carcinogenicity testing in the p53- mouse, vein irritation, and phototoxicity. No specific target organ toxicity (clinical or histopathological), reproductive toxicity, or carcinogenicity was observed. S-59 and/or PCT formulations demonstrated CNS, ECG, and phototoxicity only at supraclinical doses. Based on the extremely large safety margins (>30,000 fold expected clinical exposures), the CNS and ECG observations are not considered to have any toxicological relevance. Additionally, after a complete assessment, mutagenicity and phototoxicity results are not considered relevant for the proposed use of INTERCEPT platelets. Thus, the results of an extensive series of in vitro and in vivo studies have not demonstrated any toxicologically relevant effects of platelet concentrates prepared by the INTERCEPT system.

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