Reproductive and Developmental Toxicity of Arsenic in Rodents: A Review

2006 ◽  
Vol 25 (5) ◽  
pp. 319-331 ◽  
Author(s):  
Amy Wang ◽  
Steven D. Holladay ◽  
Douglas C. Wolf ◽  
S. Ansar Ahmed ◽  
John L. Robertson
Keyword(s):  
Drinking Water ◽  
Developmental Toxicity ◽  
Fetal Brain ◽  
Inorganic Arsenic ◽  
In Vivo Studies ◽  
Laboratory Animals ◽  
Population Exposure ◽  
High Dose ◽  
Oral Gavage

Arsenic is a recognized reproductive toxicant in humans and induces malformations, especially neural tube defects, in laboratory animals. Early studies showed that murine malformations occurred only when a high dose of inorganic arsenic was given by intravenous or intraperitoneal injection in early gestation. Oral gavage of inorganic arsenic at maternally toxic doses caused reduced fetal body weight and increased resorptions. Recently, arsenic reproductive and developmental toxicity has been studied in situations more similar to human exposures and using broader endpoints, such as behavioral changes and gene expression. For the general population, exposure to arsenic is mostly oral, particularly via drinking water, repeated and prolonged over time. In mice and rats, methylated or inorganic arsenic via drinking water or by repeated oral gavage induced male and female reproductive and developmental toxicities. Furthermore, at nonmaternally toxic levels, inorganic arsenic given to pregnant dams via drinking water affected fetal brain development and postnatal behaviors. However, arsenic given by repeated oral gavage to pregnant mice and rats was not morphologically teratogenic. In this review of arsenic reproductive and developmental toxicity in rats and mice, the authors summarize recent in vivo studies and discuss possible underlying mechanisms. The influences of folate, selenium, zinc, and arsenic methylation on arsenic reproductive and developmental toxicity are also discussed.

scholarly journals Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Hep G2 ◽  
Time Curve ◽  
Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

scholarly journals CD44 Targeted Nanomaterials for Treatment of Triple-Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 898
Author(s):  
Ghazal Nabil ◽  
Rami Alzhrani ◽  
Hashem Alsaab ◽  
Mohammed Atef ◽  
Samaresh Sau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
In Vivo Studies ◽  
High Dose ◽  
Luminal A ◽  
Combination Strategy ◽  
Ongoing Research

Identified as the second leading cause of cancer-related deaths among American women after lung cancer, breast cancer of all types has been the focus of numerous research studies. Even though triple-negative breast cancer (TNBC) represents 15–20% of the number of breast cancer cases worldwide, its existing therapeutic options are fairly limited. Due to the pivotal role of the presence/absence of specific receptors to luminal A, luminal B, HER-2+, and TNBC in the molecular classification of breast cancer, the lack of these receptors has accounted for the aforementioned limitation. Thereupon, in an attempt to participate in the ongoing research endeavors to overcome such a limitation, the conducted study adopts a combination strategy as a therapeutic paradigm for TNBC, which has proven notable results with respect to both: improving patient outcomes and survivability rates. The study hinges upon an investigation of a promising NPs platform for CD44 mediated theranostic that can be combined with JAK/STAT inhibitors for the treatment of TNBC. The ability of momelotinib (MMB), which is a JAK/STAT inhibitor, to sensitize the TNBC to apoptosis inducer (CFM-4.16) has been evaluated in MDA-MB-231 and MDA-MB-468. MMB + CFM-4.16 combination with a combination index (CI) ≤0.5, has been selected for in vitro and in vivo studies. MMB has been combined with CD44 directed polymeric nanoparticles (PNPs) loaded with CFM-4.16, namely CD44-T-PNPs, which selectively delivered the payload to CD44 overexpressing TNBC with a significant decrease in cell viability associated with a high dose reduction index (DRI). The mechanism underlying their synergism is based on the simultaneous downregulation of P-STAT3 and the up-regulation of CARP-1, which has induced ROS-dependent apoptosis leading to caspase 3/7 elevation, cell shrinkage, DNA damage, and suppressed migration. CD44-T-PNPs showed a remarkable cellular internalization, demonstrated by uptake of a Rhodamine B dye in vitro and S0456 (NIR dye) in vivo. S0456 was conjugated to PNPs to form CD44-T-PNPs/S0456 that simultaneously delivered CFM-4.16 and S0456 parenterally with selective tumor targeting, prolonged circulation, minimized off-target distribution.

The potential reproductive effects of exposure of domestic ruminants to endocrine disrupting compounds

2002 ◽  
Vol 74 (1) ◽  
pp. 3-12 ◽  
Author(s):  
M.L. Boerjan ◽  
S. Freijnagel ◽  
S.M. Rhind ◽  
G.A.L. Meijer
Keyword(s):  
Drinking Water ◽  
Reproductive Function ◽  
Endocrine Disrupting Compounds ◽  
Laboratory Animals ◽  
Domestic Ruminants ◽  
Reproductive Effects ◽  
Endocrine Disrupting ◽  
Contaminated Food

AbstractChemical compounds that mimic or block some of the actions of the steroid hormone oestradiol, have created public concern primarily because of potential adverse reproductive effects in wildlife and humans. Many studies, in vivo and in vitro, have revealed abnormal reproductive function following exposure to these compounds. The number of chemicals known to have the potential to modulate endocrine functions is increasing. In contrast to humans and wildlife, the potential reproductive effects of exposure of domestic animals to endocrine disrupting compounds (EDC) have been studied little. The aim of this overview is to evaluate the possible contribution of EDC to reproductive failure in domestic ruminants.Sources and classes of EDC are discussed as well as their structure and the modes of hormone disruption. Endocrine disrupting agents may interfere with the reproductive processes of both males and females at several points of the reproductive cycle and through a range of physiological mechanisms. Extrapolating from the results obtained with laboratory animals, the mechanisms whereby infertility in domestic ruminants might be expressed by exposure to EDC through contaminated food and drinking water are addressed.A preliminary risk assessment is included and it is concluded that under certain circumstances there may be a significantly enhanced intake of oestrogenic hormones and EDC through sewage-contaminated water or soil-contaminated herbage. The physiological consequences for domestic ruminants of EDC ingestion, at the rates estimated, are largely unknown. However, the levels of exposure to oestrogenic hormones and phthalates in grazing ruminants are such that when studying fertility problems in high-yielding dairy cattle the impacts of exposure to endocrine disruptors via the food and drinking water cannot be neglected.

scholarly journals In vivo studies of the role of factor VII in hemostasis

Blood ◽  
1985 ◽  
Vol 65 (5) ◽  
pp. 1197-1200
Author(s):  
AR Giles ◽  
S Tinlin ◽  
L Brosseau ◽  
H Hoogendoorn
Keyword(s):  
Alternative Pathway ◽  
Factor Xa ◽  
In Vivo Studies ◽  
Factor Vii ◽  
High Dose ◽  
Factor X ◽  
Clotting Factors ◽  
Dose Warfarin ◽  
Factor X Activation

The effect of both congenital and acquired factor VII deficiency on the cuticle bleeding time (CBT) was evaluated in dogs. The CBT has been previously documented to be a sensitive indicator of factor VIII:C deficiency in hemophilic dogs. Serial CBT determinations were made on normal dogs treated with high-dose warfarin. At 48 hours post- treatment, the CBT was normal, although the factor VII level was less than 1%, whereas the levels of factors II, IX, and X were 44%, 25%, and 17%, respectively. At 120 hours the CBT became abnormal when all vitamin K-dependent clotting factors had dropped to less than 18%. Administration of a plasma concentrate of factors II, IX, and X corrected the CBT, despite the factor VII level remaining at less than 1%. Similar studies in a congenitally factor VII-deficient dog (factor VII less than 2%) confirmed that this deficiency state was not associated with an abnormality of the CBT. Administration of heparin to both normal and factor VII-deficient animals was associated with prolongation of the CBT, but the heparin dose required in the normal animals was substantially higher than in the factor VII-deficient animals. These data do not suggest that factor VII/VIIa has an exclusive role in generating factor Xa, either directly or indirectly, by way of factor IXa generation, in vivo. However, the increase in heparin sensitivity of the factor VII-deficient animals does suggest that factor VII/VIIa may, in some circumstances, present a significant alternative pathway of factor X activation, although the activation pathway involved cannot be determined from the studies performed.

scholarly journals Doxorubicin-induced myocardial failure in rats with malignant neoplasm: Protective role of fullerenol C60(OH)24

2008 ◽  
Vol 62 (3) ◽  
pp. 197-204 ◽  
Author(s):  
Rade Injac ◽  
Aleksandar Djordjevic ◽  
Borut Strukelj
Keyword(s):  
Untreated Control ◽  
Malignant Neoplasm ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Untreated Control Group ◽  
Cardiac Damage

The therapeutic utility of the anthracycline antibiotic doxorubicin is limited due to its cardiotoxicity. Our aim was to investigate the efficacy of fullerenol C60(OH)24 in preventing single, high-dose doxorubicin-induced cardiotoxicity in rats with malignant neoplasm. In vitro and in vivo studies have shown that fullerenol C60(OH)24, has strong antioxidative potential. Experiment was performed on adult female Sprague Dawley rats with chemically induced mammary carcinomas. All 32 rats (2-5 groups) received i.p. applications of 1-methyl-l-nitrosourea (MNU; 50 mg/kg body weight) on the 50th and 113th day of age. Animals were randomly divided into five groups as follows: (1) Untreated control group - rats received saline only; (2) Cancer control group - rats received MNU and saline; (3) Dox group - rats received MNU and Dox 8 mg/kg; (4) Full/Dox group -rats received MNU and Full 100 mg/kg 30 min before Dox 8 mg/kg; (5) Full group - rats received MNU and Full 100 mg/kg. Tumor incidence was 4.94 +- 0.576 per rat. The animals were sacrificed 2 days after the application of doxorubicin and/or fullerenol, and the serum activities of CK, LDH and ?-HBDH, as well as the levels of MDA, GSH, GSSG, GSH-Px, SOD, CAT, GR and TAS in the heart, were determined. The results obtained from the enzymatic activity in the serum show that the administration of a single dose of 8 mg/kg in all treated groups induces statistically significant damage. There are significant changes in the enzymes of LDH and CK (p < 0.05), after an i.p. administration of doxorubicin/fullerenol and fullerenol. Comparing all groups with untreated control group, point to the conclusion that in the case of a lower oc-HBDH/LDH ratio, results in more serious the liver parenchymal damage. The results revealed that doxorubicin induced oxidative damage and that the fullerenol antioxidative influence caused significant changes in MDA, GSH, GSSG, GSH-Px, SOD, CAT, GR and TAS level in the heart (p < 0.05). Ultra structural analysis of heart tissues from rats treated with doxorubicin and indicated that the hearts of the rats were protected from doxorubicin-induced subcellular damage. Doxorubicin/fullerenol rats did not appear to show significant cardiac damage although occasional focal loss of cristae in the mitochondria was observed. Therefore, it is suggested that fullerenol might be a potential cardioprotector in doxorubicin-treated individuals.

IN VIVO STUDIES ON ANTISTAPHYLOCOCCAL PENICILLINASE SERUM

1964 ◽  
Vol 10 (4) ◽  
pp. 507-512
Author(s):  
M. Goldner ◽  
R. J. Wilson
Keyword(s):  
Staphylococcus Aureus ◽  
Combined Treatment ◽  
Rabbit Antiserum ◽  
Staphylococcal Infection ◽  
In Vivo Studies ◽  
Laboratory Animals ◽  
Single Strain ◽  
Lethal Doses ◽  
Observation Period

Several workers have shown that laboratory animals are protected from penicillin-resistant Staphylococcus aureus infections by antiserum to Bacillus cereus penicillinase in conjunction with benzylpenicillin. This paper shows that antiserum to staphylococcal penicillinase has the same effect. Concentrated penicillinase from a single strain of staphylococcus was used to prepare a rabbit antiserum. Groups of rabbits were injected intravenously with lethal doses of the same strain of staphylococcus. They were either given no treatment or were treated with penicillin only, antiserum only, or combined penicillin and antiserum. Antiserum was given in a single dose or in multiple doses. Throughout the 3-week observation period, the mortality in the group of rabbits receiving combined treatment was significantly less than in any other group. It was concluded that it might be possible to use antistaphylococcal penicillinase serum in the treatment of penicillin-resistant staphylococcal infection.

scholarly journals Determining the Polymer Threshold Amount for Achieving Robust Drug Release from HPMC and HPC Matrix Tablets Containing a High-Dose BCS Class I Model Drug: In Vitro and In Vivo Studies

2014 ◽  
Vol 16 (2) ◽  
pp. 398-406 ◽  
Author(s):  
Uroš Klančar ◽  
Saša Baumgartner ◽  
Igor Legen ◽  
Polona Smrdel ◽  
Nataša Jeraj Kampuš ◽  
...  
Keyword(s):  
Drug Release ◽  
Matrix Tablets ◽  
Class I ◽  
In Vivo Studies ◽  
High Dose ◽  
Model Drug ◽  
Threshold Amount

Effect of ketoconazole on adrenocorticotrophic hormone secretion in vitro and in vivo

1986 ◽  
Vol 108 (1) ◽  
pp. 37-41 ◽  
Author(s):  
J. M. Burrin ◽  
T. H. Yeo ◽  
M. J. Ashby ◽  
S. R. Bloom
Keyword(s):  
Hormone Secretion ◽  
Plasma Corticosterone ◽  
In Vivo Studies ◽  
High Dose ◽  
Direct Effects ◽  
Acth Secretion ◽  
Steroid Synthesis ◽  
Oral Doses ◽  
Adrenalectomized Rats

ABSTRACT The direct effects of ketoconazole on ACTH secretion have been investigated using a rat pituitary cell culture system. Ketoconazole had no significant effects on basal ACTH secretion, corticotrophin-releasing factor- or arginine vasopressin-stimulated ACTH secretion, nor did it affect dexamethasone inhibition of ACTH secretion. In-vivo studies demonstrated an increased ACTH level (168 vs 76 ng/l) accompanied by a fall in plasma corticosterone (193 vs 307 μg/l) in normal rats given ketoconazole (24 mg/kg, five oral doses given 8 hourly). No effects were seen in adrenalectomized rats or at lower doses (6 mg/kg) in normal or adrenalectomized rats. A high dose of ketoconazole (24 mg/kg, twice daily oral doses) also caused increased ACTH levels in normal rats (129 vs 86 ng/l) when given for 7 days. No effects were seen in adrenalectomized rats or on plasma corticosterone levels in normal rats. Our data suggest that ketoconazole at these doses has no direct effects on pituitary ACTH secretion but causes an increase in plasma ACTH due to its inhibition of adrenal steroid synthesis. J. Endocr. (1986) 108, 37–41

Histomorphometric Analysis: Effects of Simvastatin on Bone Mass, Microarchitecture and Turnover in Normal Rat

2013 ◽  
Vol 302 ◽  
pp. 26-30
Author(s):  
Fa Ming Tian ◽  
Liu Zhang ◽  
Hui Zhang ◽  
Jie Zheng ◽  
Da Cheng Han ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Mineral ◽  
Bone Histomorphometry ◽  
In Vivo Studies ◽  
High Dose ◽  
Mineral Density ◽  
Reductase Inhibitors

Simvastatin, as one of the HMG-CoA reductase inhibitors for lowering lipids, has been demonstrated its potential benefit in bone formation, which was, however, conflicting and inconclusive in vivo studies. Thus, we performed this study to assess the in vivo effects of simvastatin on bone formation. Six-week old rats were administered with simvastatin (20 mg/kg/d) or vehicle for 6 or 9 weeks. All animals were sacrificed one day after the final administration. The left femora were removed for the measurement of bone histomorphometry and bone mineral density (BMD).Compared to the control groups, on both 6th week and 9th week, bone mineral density and bone histomorphometry detected no significant differences in bone mass and microarchitecture in simvastatin treatment group, as well as bone formatin/resorption parameters. These results indicate that simvastatin had no positive effect or impact on bone in rats administered with high dose simvastatin (20 mg/kg/d) for 6 or 9 weeks.

scholarly journals Preclinical molecular imaging: development of instrumentation for translational research with small laboratory animals

2016 ◽  
Vol 14 (3) ◽  
pp. 408-414 ◽  
Author(s):  
Jorge Mejia ◽  
Ana Claudia Camargo Miranda ◽  
Ana Claudia Ranucci Durante ◽  
Larissa Rolim de Oliveira ◽  
Marycel Rosa Felisa Figols de Barboza ◽  
...  
Keyword(s):  
Spatial Resolution ◽  
Gamma Camera ◽  
Large Scale ◽  
In Vivo Studies ◽  
Laboratory Animals ◽  
Operational Parameters ◽  
Combined System ◽  
Adult Rats ◽  
Tomographic Images

ABSTRACT Objective: To present the result of upgrading a clinical gamma-camera to be used to obtain in vivo tomographic images of small animal organs, and its application to register cardiac, renal and neurological images. Methods: An updated version of the miniSPECT upgrading device was built, which is composed of mechanical, electronic and software subsystems. The device was attached to a Discovery VH (General Electric Healthcare) gamma-camera, which was retired from the clinical service and installed at the Centro de Imagem Pré-Clínica of the Hospital Israelita Albert Einstein. The combined system was characterized, determining operational parameters, such as spatial resolution, magnification, maximum acceptable target size, number of projections, and acquisition and reconstruction times. Results: Images were obtained with 0.5mm spatial resolution, with acquisition and reconstruction times between 30 and 45 minutes, using iterative reconstruction with 10 to 20 iterations and 4 projection subsets. The system was validated acquiring in vivo tomographic images of the heart, kidneys and brain of normal animals (mice and adult rats), using the radiopharmaceuticals technetium-labeled hexakis-2-methoxy-isobutyl isonitrile (99mTc-Sestamibi), technetium-labeled dimercaptosuccinic acid (99mTc-DMSA) and technetium-labeled hexamethyl propyleneamine oxime (99mTc-HMPAO). Conclusion: This kind of application, which consists in the adaptation for an alternative objective of already existing instrumentation, resulted in a low-cost infrastructure option, allowing to carry out large scale in vivo studies with enhanced quality in several areas, such as neurology, nephrology, cardiology, among others.

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