Exploration of cytotoxic and genotoxic endpoints following sub-chronic oral exposure to titanium dioxide nanoparticles

2019 ◽  
Vol 35 (9) ◽  
pp. 577-592 ◽  
Author(s):  
Srijita Chakrabarti ◽  
Danswrang Goyary ◽  
Sanjeev Karmakar ◽  
Pronobesh Chattopadhyay
Keyword(s):  
Titanium Dioxide ◽  
Titanium Dioxide Nanoparticles ◽  
Flow Cytometric Analysis ◽  
Raw 264.7 Cells ◽  
Oral Exposure ◽  
Chromosomal Breakage ◽  
Flow Cytometric ◽  
Higher Doses

Health hazards of titanium dioxide nanoparticles (TiO2-NPs) have raised severe concerns because of the paucity of information regarding the toxic effects among the population. In the present research, the in vitro and in vivo cytotoxic potential of TiO2-NPs were evaluated using flow cytometric techniques. Further, in vitro and in vivo genotoxic endpoints were estimated by means of comet, micronucleus (MN), and chromosomal aberration (CA) assays. In vitro analysis was performed at the concentration range of 10–100 µg/mL using murine RAW 264.7 cells. In vivo experiments were conducted on Albino mice (M/F) by exposing them to 200 and 500 mg/kg TiO2-NPs for 90 days. Decreased percentage of cell viability with higher doses of TiO2-NPs was evident in both in vitro and in vivo flow cytometric analysis. Further, an impaired cell cycle (G0/G1, S, and G2/M) was reflected in the present investigation following the exposure to TiO2-NPs. Increased comet scores such as tail length, % DNA in tail, tail moment, and olive moment were also observed with the higher doses of TiO2-NPs in vitro and in vivo comet assays. Finally, the in vivo MN and CA assays revealed the formation of MN and chromosomal breakage following the exposure to TiO2-NPs.

scholarly journals Quercetin and Idebenone Ameliorate Oxidative Stress, Inflammation, DNA damage, and Apoptosis Induced by Titanium Dioxide Nanoparticles in Rat Liver

Dose-Response ◽  
2018 ◽  
Vol 16 (4) ◽  
pp. 155932581881218 ◽  
Author(s):  
Laila M. Fadda ◽  
Hanan Hagar ◽  
Azza M. Mohamed ◽  
Hanaa M. Ali
Keyword(s):  
Titanium Dioxide ◽  
Histopathological Examination ◽  
Titanium Dioxide Nanoparticles ◽  
Reactive Protein ◽  
Wide Range ◽  
Factor Α ◽  
Immunoglobin G ◽  
Endothelial Growth Factor

Titanium dioxide nanoparticles (TiO2-NPs) are extensively used in a wide range of applications; however, many reports have investigated their nanotoxicological effect at the molecular level either in vitro or in vivo systems. The defensive roles of quercetin (Qur) or idebenone (Id) against the hepatotoxicity induced by TiO2-NPs were evaluated in the current study. The results showed that the coadministration of Qur or Id to rats intoxicated with TiO2-NPs markedly ameliorated the elevation in hepatic malondialdehyde (MDA), serum alanine amino-transferase (ALT), glucose, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), immunoglobin G (IgG), and C-reactive protein (CRP) levels compared to their levels in TiO2-NPs-treated rats. The aforementioned antioxidants also effectively modulated the changes in the levels of serum vascular endothelial growth factor (VEGF), nitric oxide (NO), hepatic DNA breakage, caspase-3, and inhibition of drug metabolizing enzymes (cytochrome P450s; CYP4502E12E1) in rat livers induced by TiO2-NPs toxicity. The histopathological examination of the liver section showed that TiO2-NPs caused severe degeneration of most hepatocytes with an increase in collagen in the portal region, while treatment with the antioxidants in question improved liver architecture. These outcomes supported the use of Qur and Id as protective agents against the hepatotoxicity induced by TiO2-NPs and other hepatotoxic drugs.

scholarly journals Agglomeration of titanium dioxide nanoparticles increases toxicological responses in vitro and in vivo

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Sivakumar Murugadoss ◽  
Frederic Brassinne ◽  
Noham Sebaihi ◽  
Jasmine Petry ◽  
Stevan M. Cokic ◽  
...  
Keyword(s):  
Titanium Dioxide ◽  
Titanium Dioxide Nanoparticles

High-resolution tracking of cell division suggests similar cell cycle kinetics of hematopoietic stem cells stimulated in vitro and in vivo

Blood ◽  
2000 ◽  
Vol 95 (3) ◽  
pp. 855-862 ◽  
Author(s):  
Robert A. J. Oostendorp ◽  
Julie Audet ◽  
Connie J. Eaves
Keyword(s):  
Stem Cells ◽  
Fetal Liver ◽  
Flow Cytometric Analysis ◽  
Hematopoietic Stem ◽  
Murine Bone Marrow ◽  
Flow Cytometric ◽  
Differentiation Status ◽  
Kinetics Of

The kinetics of proliferation of primitive murine bone marrow (BM) cells stimulated either in vitro with growth factors (fetal liver tyrosine kinase ligand 3 [FL], Steel factor [SF], and interleukin-11 [IL-11], or hyper–IL-6) or in vivo by factors active in myeloablated recipients were examined. Cells were first labeled with 5- and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE) and then incubated overnight prior to isolating CFSE+ cells. After 2 more days in culture, more than 90% of the in vivo lymphomyeloid repopulating activity was associated with the most fluorescent CFSE+ cells (ie, cells that had not yet divided), although this accounted for only 25% of the repopulating stem cells measured in the CFSE+ “start” population. After a total of 4 days in culture (1 day later), 15-fold more stem cells were detected (ie, 4-fold more than the day 1 input number), and these had become (and thereafter remained) exclusively associated with cells that had divided at least once in vitro. Flow cytometric analysis of CFSE+ cells recovered from the BM of transplanted mice indicated that these cells proliferated slightly faster (up to 5 divisions completed within 2 days and up to 8 divisions completed within 3 days in vivo versus 5 and 7 divisions, respectively, in vitro). FL, SF, and ligands which activate gp130 are thus efficient stimulators of transplantable stem cell self-renewal divisions in vitro. The accompanying failure of these cells to accumulate rapidly indicates important changes in their engraftment potential independent of accompanying changes in their differentiation status.

Titanium dioxide nanoparticles tested for genotoxicity with the comet and micronucleus assays in vitro, ex vivo and in vivo

2019 ◽  
Vol 843 ◽  
pp. 57-65 ◽  
Author(s):  
Alena Kazimirova ◽  
Magdalena Baranokova ◽  
Marta Staruchova ◽  
Martina Drlickova ◽  
Katarina Volkovova ◽  
...  
Keyword(s):  
Titanium Dioxide ◽  
Ex Vivo ◽  
Titanium Dioxide Nanoparticles

Human in vivo and in vitro studies on gastrointestinal absorption of titanium dioxide nanoparticles

2015 ◽  
Vol 233 (2) ◽  
pp. 95-101 ◽  
Author(s):  
Kate Jones ◽  
Jackie Morton ◽  
Ian Smith ◽  
Kerstin Jurkschat ◽  
Anne-Helen Harding ◽  
...  
Keyword(s):  
Titanium Dioxide ◽  
Titanium Dioxide Nanoparticles ◽  
In Vitro Studies ◽  
Gastrointestinal Absorption

The cytotoxic and immunomodulatory effects of titanium dioxide nanoparticles and Sargassum oligocystum on Toxoplasma gondii in vitro and in vivo.

2020 ◽  
Vol 18 ◽  
Author(s):  
Negar Asadi ◽  
Shahram Khademvatan ◽  
Habib Mohammadzadeh ◽  
Behnam Heshmatiyan ◽  
Sadegh Asghari ◽  
...  
Keyword(s):  
Titanium Dioxide ◽  
Titanium Dioxide Nanoparticles ◽  
Combined Treatment ◽  
Challenge Test ◽  
Annexin V ◽  
Life Time ◽  
Antiparasitic Activity ◽  
Treatment Experiment

Objective: This study was undertaken to evaluate the effect of titanium dioxide (TiO2) nanoparticles (NPs) and methanolic extract of Persian Gulf brown algae (Sargassum oligocystum) on the growth and cell death of T. gondii tachyzoites in vitro and in vivo. Methods: Six to eightweekold female BALB/c mice (n = 28) were used for the treatment experiment and infected with 105 T. gondii tachyzoites. Four days after treatment, IFN-γ and the levels of splenic lymphocyte proliferation were measured. All the groups were challenged with T. gondii, and the survival rate of experimental mice was assessed. The effects of TiO2NPs and S. oligocystum on the proliferation of T. gondii were evaluated by MTT and annexin V staining in vitro. Results: Based on the results, the combination of S. oligocystum extract and TiO2NPs had more cytotoxic effect compared to their use separately. The results of challenge test also revealed that mice received combined treatment had the highest life time expectancy than those receiving the treatment alone. Conclusion: The simultaneous use of immunomodulatory compounds for the stimulation of the immune system as well as S. oligocystum and TiO2NPs with antiparasitic activity can be promising to develop an effective drug for the treatment of toxoplasmos.

Mesenchymal Stromal Cells Expressing Interferon α Limit the Development of Acute Myeloid Leukemia, Inducing Apoptosis In Vitro and In Vivo

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5216-5216
Author(s):  
Laura M Desbourdes ◽  
Adam J Guess ◽  
Suheyla Hasgur ◽  
Kathleen M Overholt ◽  
Minjun Yu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Myeloid Leukemia ◽  
Stromal Cells ◽  
Myeloid Leukemia ◽  
Flow Cytometric Analysis ◽  
Interferon Α ◽  
Flow Cytometric ◽  
Acute Myeloid

Abstract Introduction The 5-year survival for patients with acute myeloid leukemia (AML) has stagnated for over two decades at about 60% for children, 40% for young adults, and <15% for elderly patients. While most patients achieve remission, approximately 50% will relapse which is generally attributed to the persistence of leukemic stem cells. Interferon α (IFNα) is an effective therapy for patients with AML due to multiple mechanisms of action. However, high serum levels are associated with many adverse effects. In this proof-of-concept study, we used engineered mesenchymal stem/stromal cells (MSC) to deliver high concentrations of IFNα locally to an AML chloroma, potentially diminishing the poorly tolerated systemic side-effects. Methods Bone marrow MSCs from C57BL/6 mouse were isolated and transduced with a lentiviral vector expressing murine IFNα (IFNα-MSCs) and/or GFP (GFP MSCs). After measuring IFNα secretion by ELISA and confirming activity by the induction of the MHC I expression on the transduced cells, the anti-AML activity of these transduced MSCs was assessed by co-culture with the C57BL/6 AML cell line c1498 which expresses DsRed and firefly luciferase (FFluc). Apoptotic cell frequencies and cell cycle phase distributions of leukemia cells with or without MSCs were assessed by flow cytometry. The in vivo validation has been performed by subcutaneous injection of c1498 cells (chloroma) with or without GFP MSCs or IFNα MSCs in C57BL/6 mice. Tumor growth was monitored by bioluminescence imaging every 3 or 4 days. Results Flow cytometric analysis and ELISA confirmed the secretion of bio-active of IFNα by transduced MSCs (41.5 ng/1E06 MSCs/24h). In co-cultures, the presence of IFNα MSCs at the ratio 100:1 (c1498: MSC) significantly decreased the population of c1498 cells mainly by inducing apoptosis compared to MSC-free or GFP MSC co-cultures while no effect was observed on cell cycle distribution. The pro-apoptotic effect of IFNα MSCs was then investigated in vivo by subcutaneous injection of c1498 cells with or without MSCs (ratio 10:1) in C57BL/6 mice.The presence of IFNα MSCs significantly decreased leukemic cell mass as shown by the bioluminescence of the DsRed+ FFLuc+ c1498 cells. This result was confirmed by flow cytometric analysis of the percentage of DsRed + cells in the chloroma. Conclusions This study shows that IFNα MSCs present a strong anti-leukemic effect in vitro and in vivo promoting apoptosis and thus decreasing the leukemic burden. Further experiments will focus on a potential synergetic effect with Cytarabine treatment and a preclinical study using human IFNα MSCs in a xenograft murine model. Disclosures No relevant conflicts of interest to declare.

Flow Cytometric Analysis of R3327 Rat Prostate Adenocarcinoma Grown in Vivo and in Vitro

1983 ◽  
Vol 129 (6) ◽  
pp. 1282-1283
Author(s):  
A.J. Claflin ◽  
A. Pollack ◽  
T. Malinin ◽  
N.L. Block ◽  
G.L. Irvin
Keyword(s):  
Flow Cytometric Analysis ◽  
Prostate Adenocarcinoma ◽  
Flow Cytometric ◽  
Rat Prostate

scholarly journals Indole hydrazide compound ZJQ-24 inhibits angiogenesis and induces apoptosis cell death through abrogation of AKT/mTOR pathway in hepatocellular carcinoma

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Jing Liu ◽  
Ying Liu ◽  
Jianqiang Zhang ◽  
Dan Liu ◽  
Yafeng Bao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Scientific Evidence ◽  
Flow Cytometric Analysis ◽  
Xenograft Model ◽  
Mtor Pathway ◽  
Flow Cytometric ◽  
M Phase

Abstract Angiogenesis and the activation of AKT/mTOR pathway are crucial for hepatocarcinoma development and progression, the activation of mTORC1/2 and relevant substrates have been confirmed in clinical hepatocarcinoma samples. Therefore, AKT/mTOR pathway represents the major targets for anti-cancer drugs development. Here, we investigated the anti-proliferative activity and mechanisms of ZJQ-24 in hepatocellular carcinoma, both in vivo and in vitro. A hepatocellular carcinoma xenograft model showed that ZJQ-24 significantly inhibited tumor growth with few side effects. MTT assays, flow cytometric analysis, Western blotting and immunohistochemistry identified that ZJQ-24 effectively suppressed hepatocellular carcinoma cell proliferation via G2/M phase arrest and caspase-dependent apoptosis but had no cytotoxic on normal cells. Furthermore, ZJQ-24 significantly blocked AKT/mTOR signaling by down-regulation of mTORC1 molecules, including phospho-p70S6K (Thr389) and phospho-4EBP-1 (Ser65, Thr37/46, Thr70) and phospho-AKT (Ser473) in HCC cells. It is very important that the ZJQ-24 did not induce the mTORC1-depdent PI3K/Akt feedback activation through JNK excitation. Moreover, ZJQ-24 inhibited the cap-dependent translation initiation by impairing the assembly of the eIF4E/eIF4G complex. Immunohistochemistry further confirmed ZJQ-24 inhibited the tumor growth through suppression of VEGF and AKT/mTOR pathways in vivo. Thus, the present study is the first to illustrate that ZJQ-24 triggers antiangiogenic activity and apoptosis via inhibiting the AKT/mTOR pathway in hepatocellular carcinoma cells, providing basic scientific evidence that ZJQ-24 shows great potential function as inhibitor of angiogenesis and tumor growth in hepatocellular carcinoma.

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