scholarly journals Antigenotoxic potential of gel extract of Aloe vera against Sodium azide genotoxicity in Allium cepa cells

2021 ◽  
pp. 1-5
Author(s):  
Akeem Akinboro ◽  
Aisha Jimoh
Keyword(s):  
Cell Division ◽  
Allium Cepa ◽  
Sodium Azide ◽  
Dose Range ◽  
Aloe Vera ◽  
Dependent Manner ◽  
Root Tips ◽  
Aloe Vera Gel ◽  
Lower Dose Range ◽  
Dose Dependent

Nowadays, the increasing rate of human exposure to various kinds of environmental mutagens has necessitated the search for natural antimutagens /antigenotoxic agents in natural products. In this study, Aloe vera gel extract was tested for its possible antigenotoxicity following the Allium cepa assay. Ten onions (Allium cepa) per dose were grown for 48 and 72 hours on gel extract of A. vera at 6.25%, 12.5%, 25.0%, 50.0% and 100.0% in combination with sodium azide (0.05mg/ml) solution for microscopic and macroscopic evaluations, respectively. Distilled water and sodium azide were the negative and positive controls, respectively. The cell division in the root tips, and root growth in the exposed A. cepa were inhibited in a dose dependent manner by the mixture of A. vera and sodium azide. However, the mixture of absolute (100.0%) dose and sodium azide completely arrested cell division and induced a lower root length than that recorded for sodium azide alone. The genotoxicity of sodium azide was inversely reduced by the doses of A. vera except at 100.0%. These results show that gel extract of A. vera possesses strong antigenotoxic /antimutagenic potency at lower dose range of 6.25% to 25.0% in A. cepa cells, however, its higher doses above 50.0% to 100.0% could be severely toxic when being considered for suppression of environmental mutagens’ mutagenicity or genotoxicity. This suggests that gel extract of A. vera contains phytochemical(s) that can be useful in the development of anticancer drug.

scholarly journals Influence of hypoxia on protoplast structure in the plant cell

2015 ◽  
Vol 44 (3) ◽  
pp. 369-376
Author(s):  
Maria Podbielkowska ◽  
Bożena Borys
Keyword(s):  
Endoplasmic Reticulum ◽  
Nucleic Acids ◽  
Allium Cepa ◽  
Plant Cell ◽  
Rough Endoplasmic Reticulum ◽  
Sodium Azide ◽  
Root Tips ◽  
Respiratory Inhibitors ◽  
Meristematic Cells ◽  
Parallel Structures

An influence of hypoxia on the protoplast’s structure in the root tips meristematic cells of onion (<i>Allium cepa</i> L.) and of <i>Tradescantia bracteata</i> Small has been investigated. Hypoxia was caused either by respiratory inhibitors (sodium azide, 2,4-dinitrophenol), phosfon-D or by anaeroibic conditions. In both cases characteristic membranization of cytoplasm was observed. It appeared as spherical and parallel structures of rough endoplasmic reticulum. The observed hypertrophy was not connected with the increase of nucleic acids and proteins synthesis. In the examined cells the membranization was accompanied by an increase of the lipids content.

Effect of heparin and its derivatives on the progression of tumor growth in mouse Lewis lung carcinoma model.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13115-e13115
Author(s):  
Angel Gray ◽  
Debra Hoppensteadt ◽  
Matthew Hejna ◽  
Jawed Fareed
Keyword(s):  
Tumor Growth ◽  
Anticoagulant Activity ◽  
Dose Range ◽  
Saline Control ◽  
Spleen Weight ◽  
Dependent Manner ◽  
Heparin Group ◽  
Prevention Of Cancer ◽  
Cancer Associated Thrombosis ◽  
Dose Dependent

e13115 Background: Preclinical evidence suggests that heparins have an effect on tumor progression independent of their anticoagulant activity. Heparins have also been shown to exhibit interactions with growth factors and other cellular receptors. This study was designed to investigate whether heparin and its derivatives are able to inhibit tumor growth. Methods: Female C57BL/6 mice were obtained at 6-8 weeks of age and were implanted with 5X105 LN7 tumor cells by dorsal subcutaneous injection of in the upper back. When tumors were first palpable, after 7-10 days of growth, mice were treated with subcutaneous injections of heparin, a low molecular weight heparin (LMWH), namely enoxaparin, an ultra LMWH, semuloparin or saline, daily for two weeks in a dose range of 1.0 – 0.25 mg/kg. After the treatment period, animals were sacrificed and the spleens and tumors were removed and their weight, volume, spleen weight and size were measured. Results: At the 1.0 and 0.5 mg/kg dosages, both enoxaparin (p<0.01) and semuloparin (p<0.01) showed a decrease in tumor volume compared to the saline control animals. At the 1.0 mg/kg dosage, the mortality was high in the heparin group due to bleeding. At 0.5 mg/kg heparin was not different from the saline control. In addition, at a dosage of 0.25 mg/kg, only semuloparin showed a difference compared to the saline control (p<0.01). Similar results were observed for the tumor weight. There were no significant differences noted in spleen weight or spleen size among these agents. The mortality rates between the mice treated with enoxaparin and semuloparin were comparable. Conclusions: These studies suggest that heparin and its derivatives are capable of inhibiting tumor growth in a dose dependent manner. Enoxaparin and semuloparin are more effective at reducing tumor growth compared to heparin. Clinical studies have shown that semuloparin is safe and effective for the prevention of venous thromboembolism in cancer patients and compares favorably to enoxaparin in terms of antithrombotic effect and safety profile. Therefore, semuloparin may be a better alternate for the prevention of cancer associated thrombosis.

scholarly journals 1953. VE303, a Rationally Designed Bacterial Consortium for Prevention of Recurrent Clostridioides difficile (C. Difficile) infection (rCDI), Stably Restores the Gut Microbiota After Vancomycin (vanco)-Induced Dysbiosis in Adult Healthy Volunteers (HV)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S60-S60 ◽  
Author(s):  
Dmitri Bobilev ◽  
Shakti Bhattarai ◽  
Rajita Menon ◽  
Brian Klein ◽  
Shilpa Reddy ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Phase 1 ◽  
Dose Range ◽  
Bacterial Consortium ◽  
Dependent Manner ◽  
Metagenomic Sequencing ◽  
Early Recovery ◽  
Dose Escalation Study ◽  
Dose Dependent

Abstract Background Gut microbiota alterations and resulting changes in metabolites involved in colonization resistance and host responses, including bile acids (BA) and short-chain fatty acids (SCFA), are hallmarks of C. difficile infection. Reduction in rCDI was shown with fecal microbiota transplants (FMT), but FMT has limitations for routine use and carries unforeseen risks. VE303 is a first-in-class drug being developed for prevention of rCDI consisting of a rationally defined bacterial consortium manufactured under GMP conditions. VE303 comprises 8 distinct species belonging to Clostridium clusters IV, XIVa, and XVII, the commensal bacteria associated with clinical response in FMT, suppress C. difficile growth in vitro and improve survival in vivo. Methods A first-in-human Phase 1 dose-escalation study assessed safety and tolerability of VE303 in HV after vanco-induced dysbiosis. PK (strain colonization and durability) and PD (restoration of the resident microbiota, SCFA pool, and BA pool) were evaluated by metagenomic sequencing and metabolomics analysis of fecal material. Results HV (N = 23) received oral vanco 125 mg QID for 5 days followed by VE303 capsules at escalating single then multiple doses (total dose range 1.6 × 109 to 1.1 × 1011 CFU). VE303-related AEs, mostly gastrointestinal, all Grade 1 and transient, were observed in 35% of HV. Colonization with VE303 strains was abundant, durable (detected at 24 weeks), and dose-dependent. VE303 rapidly expanded 10- to 100-fold and each strain was detectable within 2 days after dosing. VE303 enhanced subjects’ microbiota and metabolic recovery after vanco treatment. When compared with the vanco-only cohort (N = 5), VE303 led to earlier and more complete recovery of beneficial taxa (eg, Bacteroidetes, Firmicutes), reduction in inflammatory taxa (e.g., Proteobacteria) (Figure 1.), and recovery of the secondary BA and SCFA pools. Conclusion VE303, a rationally designed microbial consortium, was safe, well tolerated, and efficiently restored microbiome composition after antibiotic-induced dysbiosis in a dose-dependent manner. VE303 was associated with early recovery of key PD markers of response, including microbiota composition, bile acid, and SCFA pools. A Phase 2 study of VE303 for prevention of rCDI is underway (NCT03788434). Disclosures All Authors: No reported Disclosures.

scholarly journals Evaluation of Cytotoxic and Genotoxic Effect of Acacia nilotica (L.) Delile Extract Using Allium cepa Bioassay

2020 ◽  
pp. 154-159
Author(s):  
Samah Bodowara ◽  
Fauzia El Garaboli ◽  
Salem El shatshat
Keyword(s):  
Cell Division ◽  
Allium Cepa ◽  
Chromosomal Aberrations ◽  
Genetic Material ◽  
Genotoxic Effect ◽  
Bark Extract ◽  
Root Tips ◽  
Mitotic Abnormalities ◽  
Dividing Cells ◽  
Allium Cepa Assay

The present study aimed to measure the cytotoxic and genotoxic effect of the bark of A. nilotica extract. Allium cepa assay was used to find out the effect of A. nilotica extract on chromosome structure and behavior during cell division. The root tips meristem cells were treated with different concentration of A. nilotica bark aqueous extract (0.1, 0.01 and 0.001mg/ml) for 4, 6, 12 and 24 hours, respectively. Cytological analysis revealed decreasing in cell division in all used concentration especially at high ones. The obtained results indicate that aqueous extracts of A. nilotica plant have the ability to decrease the (MI%) values with increasing the concentration at (P<0.005). All treatments have caused different kind of mitotic abnormalities and chromosomal aberrations, such as: change percentage of mitotic phases, C-mitosis, stickiness, chromosome bridges, Micronucleus and vagrant chromosome. The action of A. nilotica bark extract on the genetic material led to decrease in dividing cells number which was concentration and time depended. This inhibition of cell division was due to disturbances in nucleus as a result of inhibition of DNA synthesis. KEY WORDS: Allium cepa assay: A. nilotica: Chromosomal aberrations; MI.

Pharmacodynamic properties of the anti-IGF-IR monoclonal antibody CP-751,871 in cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3587-3587 ◽  
Author(s):  
M. N. Pollak ◽  
M. Q. Lacy ◽  
A. Lipton ◽  
L. Demers ◽  
K. Leitzel ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Human Monoclonal Antibody ◽  
Dose Range ◽  
Dependent Manner ◽  
Igf I ◽  
Dose Dependent ◽  
Igfbp 3

3587 Background: The Insulin like Growth Factor I receptor (IGF-IR), a tyrosine kinase, is widely expressed in human tissues. IGF- IR and its ligands (IGF-I and IGF-II) are expressed by many human cancers (e.g., breast, prostate, colorectal and non-small cell lung). Binding of the ligands to the IGF-IR activates key cellular signaling pathways important for stimulating cellular proliferation and inhibiting apoptosis. IGF- I and IGF-II are present in the circulation, but also locally expressed in neoplastic tissue. Bioavailability of these ligands is regulated by a family of IGF binding proteins (IGFBPs1–6). CP-751,871, a fully human monoclonal antibody, is a highly specific and potent inhibitor of IGF-IR activation. In vitro experiments show that binding of CP 751,871 to IGF-IR induces receptor internalization and degradation. This antibody has been shown to have antineoplastic activity using both in vivo and in vitro pre-clinical models. Methods: Blood samples were collected for characterization of the pharmacokinetic and pharmacodynamic properties of CP-751,871 in phase 1 trials of this agent given to cancer patients either alone or in combination with chemotherapy. The endpoints assessed included among others: CP-751,871 plasma concentrations, total and free IGF-I, IGFBP-3, soluble IGF-IR and IGF-IR expression on granulocytes and tumor cells. Results: CP 751,871 exposure increased with dose over the 800-fold dose range investigated. Pharmacokinetic profiles were consistent with target-mediated disposition. A dose-dependent downregulation of soluble IGF-IR serum concentration and IGF-IR expression was observed, with sustained inhibition for the entire dosing period (3–4 week cycles) observed at doses ≥ 1.5 mg/kg. As predicted for an agent that interferes with IGF-I action, IGF-I and IGFBP-3 serum levels were up-regulated in a similar dose-dependent manner. Conclusions: The pharmacodynamic endpoints of clinical trials provide evidence that CP-751,871 targets IGF-IR in granulocytes, tumor cells and tissues involved in regulation of the growth hormone -IGF-I axis. These data provide proof of principle for the use of CP-751,871 as a first-in-class therapeutic approach to inhibit the IGF-IR pathway in cancer patients. No significant financial relationships to disclose.

scholarly journals Systemic Control of Cell Division and Endoreduplication by NAA and BAP by Modulating CDKs in Root Tip Cells ofAllium cepa

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Jigna G. Tank ◽  
Vrinda S. Thaker
Keyword(s):  
Cell Division ◽  
Allium Cepa ◽  
Vegetative Growth ◽  
Research Work ◽  
Colchicine Treatment ◽  
Root Tip ◽  
Root Tips ◽  
Ofallium Cepa ◽  
Elongation Process ◽  
Growth Formation

Molecular mechanism regulated by auxin and cytokinin during endoreduplication, cell division, and elongation process is studied by usingAllium cepa rootsas a model system. The activity of CDK genes modulated by auxin and cytokinin during cell division, elongation, and endoreduplication process is explained in this research work. To study the significance of auxin and cytokinin in the management of cell division and endoreduplication process in plant meristematic cells at molecular level endoreduplication was developed in root tips ofAllium cepaby giving colchicine treatment. There were inhibition of vegetative growth, formation of c-tumor at root tip, and development of endoreduplicated cells after colchicine treatment. This c-tumor was further treated with NAA and BAP to reinitiate vegetative growth in roots. BAP gave positive response in reinitiation of vegetative growth of roots from center of c-tumor. However, NAA gave negative response in reinitiation of vegetative growth of roots from c-tumor. Further, CDKs gene expression analysis from normal, endoreduplicated, and phytohormone (NAA or BAP) treated root tip was done and remarkable changes in transcription level of CDK genes in normal, endoreduplicated, and phytohormones treated cells were observed.

Effects of Neuropeptides on Mucociliary Activity

1986 ◽  
Vol 95 (1) ◽  
pp. 94-100 ◽  
Author(s):  
Sven Lindberg ◽  
Jan-Christer Hybbinette ◽  
Ulf Mercke
Keyword(s):  
Substance P ◽  
Vasoactive Intestinal Polypeptide ◽  
Dose Range ◽  
Dependent Manner ◽  
Feeding Artery ◽  
Maximal Increase ◽  
Dose Dependent ◽  
Photoelectric Technique ◽  
Intestinal Polypeptide

The effects of four neuropeptides, vasoactive intestinal polypeptide, enkephalin, bombesin, and substance P, on mucociliary activity in the rabbit maxillary sinus were investigated in vivo. The peptides were administered via the feeding artery (arteria maxillaris), and the resulting effects were registered with a noninvasive photoelectric technique. The peptides were tested in the dose range 0.0001 to 10 μg/kg body weight. The following results were observed: 1) vasoactive intestinal polypeptide and enkephalin did not influence mucociliary activity; 2) bombesin had only a slight accelerating effect on the mucociliary activity at doses of 0.1 to 10 μg/kg; and 3) substance P markedly accelerated the mucociliary activity in a dose-dependent manner in the dose range 0.01 to 10 μg/kg, the maximal increase being about 50%. The effect of substance P was atropine-resistant, and probably acted directly on the mucosa.

Centrally administered MTII affects feeding, drinking, temperature, and activity in the Sprague-Dawley rat

2000 ◽  
Vol 89 (1) ◽  
pp. 273-282 ◽  
Author(s):  
B. Murphy ◽  
C. N. Nunes ◽  
J. J. Ronan ◽  
M. Hanaway ◽  
A. M. Fairhurst ◽  
...  
Keyword(s):  
Third Ventricle ◽  
Dose Range ◽  
Behavioral Changes ◽  
Dependent Manner ◽  
Low Doses ◽  
Drinking Patterns ◽  
Sprague Dawley ◽  
Nocturnal Feeding ◽  
Dose Dependent ◽  
Higher Doses

MTII, an agonist of melanocortinergic receptors, is a well-documented anorexigenic agent in rats. Many investigators have reported its effects on feeding without considering concurrent alterations in other behaviors. Accordingly, we performed studies to simultaneously measure nocturnal feeding, drinking, activity, and temperature of rats after intracerebroventricular (third ventricle) administration of a wide dose range of MTII (0.05–500 ng). We observed that MTII modulates these physiological parameters in a dose-dependent manner. Low doses of MTII (0.05 ng) caused reductions in feeding without alterations in body temperature, drinking, or activity. In contrast, hyperthermia and disrupted drinking patterns, along with food intake reductions, were evident at doses exceeding 50 ng. The fact that low doses altered only feeding, whereas higher doses affected a range of parameters, suggests that certain melanocortin-induced behavioral changes may be mediated by distinct populations of melanocortin receptors with varying affinities or that those changes seen at higher doses may be nonspecific in nature.

scholarly journals Reversible Albumin-Binding GH Possesses a Potential Once-Weekly Treatment Profile in Adult Growth Hormone Deficiency

2016 ◽  
Vol 101 (3) ◽  
pp. 988-998 ◽  
Author(s):  
Michael Højby Rasmussen ◽  
Jurgita Janukonyté ◽  
Marianne Klose ◽  
Djordje Marina ◽  
Mette Tanvig ◽  
...  
Keyword(s):  
Adverse Events ◽  
Dose Level ◽  
Gh Deficiency ◽  
Dose Range ◽  
Control Group ◽  
Albumin Binding ◽  
Dependent Manner ◽  
Weekly Treatment ◽  
Dose Dependent ◽  
Treatment Profile

Abstract Context: NNC0195-0092 is a reversible, albumin-binding GH derivative, developed for once-weekly administration. Objectives: The objective of the study was to evaluate safety, local tolerability, pharmacodynamics, and pharmacokinetics of multiple, once-weekly doses of NNC0195-0092, compared with daily GH. Design and Setting: This was a phase 1, randomized, open-label, active-controlled, multiple-dose, dose-escalation trial. Patients: Thirty-four GH-treated adult subjects (male, n = 25) with GH deficiency participated in the study. Interventions and Main Outcome Measures: Subjects were sequentially assigned into four cohorts of eight subjects, randomized within each cohort (3:1) to once-weekly NNC0195-0092 (n = 6) for 4 weeks (0.02, 0.04, 0.08, and 0.12 mg/kg) or daily injections of Norditropin NordiFlex (n = 2) for 4 weeks with a dose replicating the pretrial dose of somatropin. A safety assessment was performed prior to initiating treatment at the next dose level of NNC0195-0092. Daily GH treatment was discontinued 14 days before the trial start. Blood samples were drawn for assessment of safety, pharmacokinetics, pharmacodynamics (IGF-1 and IGF-binding protein-3) profiles, and immunogenicity studies. Results: Numbers of adverse events were similar at the dose levels of 0.02, 0.04, and 0.08 mg/kg NNC0195-0092 vs daily injections of Norditropin NordiFlex, whereas the number of adverse events was greater at the highest dose level of NNC0195-0092 (0.12 mg/kg). NNC0195-0092 (area under the curve[0–168h]) and peak plasma concentration) increased in a dose-dependent manner, and a dose-dependent increase in IGF-1 levels was observed. IGF-1 profiles were elevated for at least 1 week, and for the 0.02-mg/kg and 0.04-mg/kg NNC0195-0092 doses, the observed IGF-1 levels were similar to the levels for the active control group. Conclusion: Four once-weekly doses of NNC0195-0092 (dose range 0.02–0.12 mg/kg) administered to adult patients with GH deficiency were well tolerated, and IGF-1 profiles were consistent with a once-weekly treatment profile. No clinically significant safety and tolerability signals causally related to NNC0195-0092 were identified, nor were any immunogenicity concerns revealed.

scholarly journals Changes in phosphorylation of histone H2A.X and p53 in response of peripheral blood lymphocytes to gamma irradiation.

2008 ◽  
Vol 55 (2) ◽  
pp. 381-390 ◽  
Author(s):  
Zdenka Vilasová ◽  
Martina Rezácová ◽  
Jirina Vávrová ◽  
Ales Tichý ◽  
Doris Vokurková ◽  
...  
Keyword(s):  
Gamma Radiation ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Kinase Inhibitor ◽  
Human Peripheral Blood ◽  
Dose Range ◽  
Dependent Manner ◽  
Pha Stimulation ◽  
Dose Dependent ◽  
Serine 392

The main aim of this study was to compare the reaction of quiescent and proliferating, i.e. phytohemagglutinin (PHA)-stimulated, human peripheral blood mononuclear cells (PBMCs) to gamma-radiation, and analyse changes of proteins related to repair of DNA damage and apoptosis, such as gammaH2A.X, p53, p53 phosphorylation at serines-15 and -392, and p21 and their dose dependence. Freshly isolated PBMCs in peripheral blood are predominantly quiescent, in G(0) phase, and with very low amounts of proteins p53 and p21. Using confocal microscopy we detected dose dependent (0.5-5 Gy) induction of foci containing gammaH2A.X (1 h after gamma-ray exposure), which are formed around radiation-induced double strand breaks of DNA. Apoptosis was detected from 24 h after irradiation by the dose of 4 Gy onwards by Annexin V binding and lamin B cleavage. Seventy two hours after irradiation 70% of CD3(+) lymphocytes were A(+). Neither increase in p53 nor its phosphorylation on serine-392 after irradiation was detected in these cells. However, massive increase in p21 (cyclin-dependent kinase inhibitor 1A) was detected after irradiation, which can be responsible for late occurrence of apoptosis in these quiescent cells. PHA-stimulation itself (72 h) caused an increase in early apoptosis (A(+)PI(-)) in comparison to non-stimulated PBMCs (38% A(+) resp. 13.4%). After PHA-stimulation also the amount of gammaH2A.X, p53, and p21 increased, but no phosphorylation of p53 on serine-392 or -15 was detected. Reaction to gamma-radiation was different in PHA-stimulated lymphocytes: the p53 pathway was activated and p53 was phosphorylated on serines-15 and -392 4 h after irradiation by the dose of 4 Gy. Phosphorylation of p53 at serine-15 increased in a dose-dependent manner in the studied dose range 0.2-7.5 Gy. Also the amount of p21 increased after irradiation. Seventy two hours after irradiation of PHA-stimulated CD3(+) T lymphocytes by the dose of 4 Gy 65% of cells were A(+).

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