Species differences in the reactivation of organophosphate-inhibited plasma esterases by diacetymonoxime

A study was conducted to assess whether the protection afforded to organophosphate-poisoned animals by diacetylmonoxime (DAM) was correlated with the reactivation of non-essential aliesterases (AliE). In vitro, the DAM-catalyzed reactivation of plasma AliE and cholinesterases (ΨChE) of rat, rabbit and guinea pig inhibited by 10−5 M diisopropylphosphorofluoridate (DFP) and O,O-dimethyl-2,2-dichlorovinyl phosphate (DDVP) was investigated. Marked reactivation of the rat plasma enzymes was achieved with 10 mM DAM. Higher concentrations (30 mM) were necessary for the slow reactivation of rabbit and guinea pig plasma AliE. Reactivation of the ΨChE of these species was comparatively slow. Reactivation of DDVP-inhibited esterases proceeded in all species at a more rapid rate than those inhibited by DFP. The dependence of ΨChE reactivation upon concomitant more rapid reactivation of AliE by DAM was demonstrated using Sephadex fractionated AliE and ΨChE but only a marked effect was observed with the rat, suggesting that the plasma AliE of this species is functionally different.The in vitro observations were confirmed by in vivo studies in rats and rabbits. DAM (50 or 150 mg/kg), administered to atropinized rats 15 min before a lethal dose of DFP, protected the animals. Few severe toxic signs were observed and reactivation of both plasma AliE and ΨChE occurred. In contrast, DAM protected the rabbit against a lethal dose of DFP but only reactivation of the erythrocyte acetylcholinesterase was observed.

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Toxicity and medical countermeasure studies on the organophosphorus nerve agents VM and VX

Proceedings of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rspa.2014.0891 ◽

2015 ◽

Vol 471 (2176) ◽

pp. 20140891 ◽

Cited By ~ 19

Author(s):

Helen Rice ◽

Christopher H. Dalton ◽

Matthew E. Price ◽

Stuart J. Graham ◽

A. Christopher Green ◽

...

Keyword(s):

Guinea Pig ◽

Penetration Rate ◽

Lethal Dose ◽

Scientific Advice ◽

Complete Protection ◽

Pig Skin ◽

Syrian Arab Republic ◽

Medical Countermeasures

To support the effort to eliminate the Syrian Arab Republic chemical weapons stockpile safely, there was a requirement to provide scientific advice based on experimentally derived information on both toxicity and medical countermeasures (MedCM) in the event of exposure to VM, VX or VM–VX mixtures. Complementary in vitro and in vivo studies were undertaken to inform that advice. The penetration rate of neat VM was not significantly different from that of neat VX, through either guinea pig or pig skin in vitro . The presence of VX did not affect the penetration rate of VM in mixtures of various proportions. A lethal dose of VM was approximately twice that of VX in guinea pigs poisoned via the percutaneous route. There was no interaction in mixed agent solutions which altered the in vivo toxicity of the agents. Percutaneous poisoning by VM responded to treatment with standard MedCM, although complete protection was not achieved.

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In vitro and in vivo studies on the selectivity of beta-adrenoceptor antagonist drugs in the guinea-pig

10.14264/uql.2015.29 ◽

1985 ◽

Author(s):

Karin Walduck

Keyword(s):

Guinea Pig ◽

In Vivo Studies ◽

Beta Adrenoceptor ◽

Adrenoceptor Antagonist

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Murine monoclonal antibodies against murine uPA receptor produced in gene-deficient mice: Inhibitory effects on receptormediated uPA activity in vitro and in vivo

Thrombosis and Haemostasis ◽

10.1160/th06-11-0644 ◽

2007 ◽

Vol 97 (06) ◽

pp. 1013-1022 ◽

Cited By ~ 14

Author(s):

Jesper Pass ◽

Annika Jögi ◽

Ida Lund ◽

Birgitte Rønø ◽

Morten Rasch ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Lethal Dose ◽

In Vivo Studies ◽

Plasminogen Activation ◽

Amino Terminal ◽

Anthrax Toxins ◽

Murine Monoclonal Antibodies ◽

Deficient Mice

SummaryBinding of urokinase plasminogen activator (uPA) to its cellular receptor, uPAR, potentiates plasminogen activation and localizes it to the cell surface. Focal plasminogen activation is involved in both normal and pathological tissue remodeling processes including cancer invasion. The interaction between uPA and uPAR therefore represents a potential target for anti-invasive cancer therapy. Inhibitors of the human uPA-uPAR interaction have no effect in the murine system. To enable in-vivo studies in murine cancer models we have now generated murine monoclonal antibodies (mAbs) against murine uPAR (muPAR) by immunizing uPAR-deficient mice with recombinant muPAR and screened for antibodies, which inhibit the muPA-muPAR interaction. Two of the twelve mAbs obtained, mR1 and mR2, interfered with the interaction between muPAR and the amino-terminal fragment of muPA (mATF) when analyzed by surface plasmon resonance. The epitope for mR1 is located on domain I of muPAR, while that of mR2 is on domains (II-III). In cell binding experiments using radiolabelled mATF, the maximal inhibition obtained with mR1 was 85% while that obtained with mR2 was 50%. The IC50 value for mR1 was 0.67 nM compared to 0.14 nM for mATF. In an assay based on modified anthrax toxins, requiring cell-bound muPA activity for its cytotoxity, a ~50% rescue of the cells could be obtained by addition of mR1. Importantly, in-vivo efficacy of mR1 was demonstrated by the ability of mR1 to rescue mice treated with a lethal dose of uPA-activatable anthrax toxins.

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Relative agonist potency as a means of differentiating α-adrenoceptors and α-adrenergic mechanisms

Clinical Science ◽

10.1042/cs068s009 ◽

1985 ◽

Vol 68 (s10) ◽

pp. 9s-15s ◽

Cited By ~ 21

Author(s):

Robert R. Ruffolo

Keyword(s):

Guinea Pig ◽

Species Differences ◽

Dissociation Constants ◽

Rat Aorta ◽

Adrenergic Mechanisms ◽

Qualitative And Quantitative ◽

Adrenoceptor Agonists ◽

Relative Potencies

1. Relative potencies (ED50), affinities (assessed as dissociation constants) and efficacies (i.e. ability to activate the receptor) of agonists are useful in subclassifying and differentiating α-adrenoceptors. 2. The postsynaptic α-adrenoceptor of rat aorta is of the α1-subtype, but may differ from the α1-adrenoceptor of rabbit and guinea pig aortae, based on comparison of relative potencies of selected agonists. 3. By evaluating the relative potency of agonists, qualitative and quantitative species differences between α1-adrenoceptors in rat and guinea pig are observed in a variety of test systems in vivo and in vitro. 4. By comparing the relative potencies of aromatic hydroxyl-substituted phenethylamines and imidazolines at α1-adrenoceptors in guinea pig aorta, differences in the ability of these two classes of α-adrenoceptor agonists to bind to, and subsequently activate, α1-adrenoceptors have been observed. 5. Evaluating the relative potencies of agonists, when used in conjunction with other techniques, provides a valuable method for classifying α-adrenoceptors and for studying α-adrenergic mechanisms.

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IN VITRO AND IN VIVO TOXICITY EVALUATION OF TRAPA BISPINOSA ROXB. STARCH

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2021.v13s1.y0109 ◽

2021 ◽

pp. 58-62

Author(s):

SURADWADEE THUNGMUNGMEE ◽

NAKUNTWALAI WISIDSRI

Keyword(s):

Lethal Dose ◽

Clinical Signs ◽

Fibroblast Cell ◽

In Vivo Studies ◽

Oral Toxicity ◽

Cosmetic Ingredients ◽

Nih 3T3 ◽

Fibroblast Cell Lines

Objective: This study aimed to assess the toxicity of Trapa bispinosa Roxb. starch (TBS) through in vitro and in vivo studies.Methods: The cytotoxicity of TBS extract (TBSE) was evaluated on RAW 264.7 macrophage and NIH 3T3 fibroblast cell lines and the acute dermal andoral toxicities of TBS were analyzed in rats. To access acute dermal toxicity, the rats received a single application of 200, 1000, and 2000 mg/kg BW ofTBS, while for acute oral toxicity, the rats received a single administration of 300 and 2000 mg/kg BW of TBS. All animals were observed for changesin body weight, mortality, and clinical signs of abnormality after application and administration of the TBS.Results: The in vitro results showed that TBSE at concentrations of 6.25–200 μg/ml was non-cytotoxic to macrophages and fibroblasts. From acutetoxicity studies, the lethal dose of TBS was considered to be over 2000 mg/kg BW. No mortality, clinical signs of abnormality, or gross pathology weredetected at necropsy.Conclusion: TBS is non-toxic in in vitro and in vivo studies. Therefore, TBS can be used as pharmaceuticals excipients or cosmetic ingredients.

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Biological Evaluation of a New Sodium-Potassium Silico-Phosphate Glass for Bone Regeneration: In Vitro and In Vivo Studies

Materials ◽

10.3390/ma14164546 ◽

2021 ◽

Vol 14 (16) ◽

pp. 4546

Author(s):

Elisa Fiume ◽

Dilshat U. Tulyaganov ◽

Avzal Akbarov ◽

Nigora Ziyadullaeva ◽

Andrea Cochis ◽

...

Keyword(s):

Lethal Dose ◽

Toxic Substance ◽

Biological Response ◽

Human Mesenchymal Stem Cells ◽

Biological Evaluation ◽

In Vivo Studies ◽

Toxicity Tests ◽

Significant Difference

In vitro and in vivo studies are fundamental steps in the characterization of new implantable materials to preliminarily assess their biological response. The present study reports the in vitro and in vivo characterizations of a novel experimental silicate bioactive glass (BG) (47.5 B, 47.5 SiO2-10 Na2O-10 K2O-10 MgO-20 CaO-2.5 P2O5 mol.%). Cytocompatibility tests were performed using human mature osteoblasts (U2OS), human mesenchymal stem cells (hMSCs) and human endothelial cells (EA.hy926). The release of the early osteogenic alkaline phosphatase (ALP) marker suggested strong pro-osteogenic properties, as the amount was comparable between hMSCs cultivated onto BG surface and cells cultivated onto polystyrene control. Similarly, real-time PCR revealed that the osteogenic collagen I gene was overexpressed in cells cultivated onto BG surface without biochemical induction. Acute toxicity tests for the determination of the median lethal dose (LD50) allowed classifying the analyzed material as a slightly toxic substance with LD50 = 4522 ± 248 mg/kg. A statistically significant difference in bone formation was observed in vivo through comparing the control (untreated) group and the experimental one, proving a clear osteogenic effect induced by the implantation at the defect site. Complete resorption of 47.5 B powder was observed after only 3 months in favor of newly formed tissue, thus confirming the high osteostimulatory potential of 47.5 B glass.

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In vitro and in vivo studies on the metabolism of estrogens and their sulfates in guinea pigs

Canadian Journal of Biochemistry ◽

10.1139/o77-054 ◽

1977 ◽

Vol 55 (4) ◽

pp. 390-397 ◽

Cited By ~ 10

Author(s):

R. Hobkirk ◽

D. J. Freeman ◽

P. R. C. Harvey ◽

Mona Nilsen ◽

Barbara Jennings

Keyword(s):

Guinea Pig ◽

Guinea Pigs ◽

Mature Male ◽

In Vivo Studies ◽

Pig Liver ◽

Male And Female ◽

Estradiol 17Β ◽

Guinea Pig Liver

Labelled estradiol-17β(E2) or estrone (E1), when incubated with guinea pig liver slices, is metabolized by two main pathways. Part of each substrate is converted to estrone-3-glucuronide and estradiol-3-glucuronide. A further part of each is metabolized to estradiol-3-sulfate (E23S) and estrone-3-sulfate (E13S), which are interconverted. The latter conjugate appears to be the substrate for a 16α-hydroxylase forming 16α-hydroxyestrone-3-sulfate (16αOHE13S). This, in turn, is further sulfurylated to yield 16α-hydroxyestrone-3,16-disulfate, accompanied by estriol-3,16-disulfate. A relatively small amount of tentatively identified '6-hydroxyestrone disulfate' accompanies these other two diconjugates. The guinea pig liver system suggests itself as a useful and relatively simple model for further study of 16α-hydroxylation of E13S. The use of the latter as a natural substrate in the system in vitro is supported by our observation that E13S and E23S are present in liver, kidney, blood, gallbladder bile, intestine, uterus, and placenta after injection of labelled E2 into mature male and female guinea pigs. Some evidence has been obtained for the disulfate fraction (above) in liver and bile after injection of labelled E1.

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Antidiarrhoeal potentials of methanol bark extract of Hymenocardia Acida Tul (Euphorbiaceae) in laboratory animals

Bulletin of the National Research Centre ◽

10.1186/s42269-021-00575-1 ◽

2021 ◽

Vol 45 (1) ◽

Author(s):

Abba Musab Usman ◽

Nuhu Muhammad Danjuma ◽

Jamilu Ya’u ◽

Muslim Muhammad Ahmad ◽

Zakariyya Alhassan ◽

...

Keyword(s):

Guinea Pig ◽

Lethal Dose ◽

Stem Bark ◽

Laboratory Animals ◽

Bark Extract ◽

Intestinal Fluid ◽

Guinea Pig Ileum ◽

Rabbit Jejunum

Abstract Background The plant Hymenocardia acida (Euphorbiaceae) is utilized as herbal preparation against diarrhoea, dysentery and other diseases. We aimed to determine the antidiarrhoeal potentials of Hymenocardia acida (MEHA) stem bark in vivo and in vitro. Preliminary phytochemical contents, as well as the acute toxicity effect of the extract, were investigated based on standard experimental methods. The antidiarrhoeal properties of the MEHA at 150, 300 and 600 mg/kg were studied against diarrhoea induced by castor oil, intestinal fluid accumulation, as well as intestinal movement tests using distilled water (10 ml/kg) and loperamide/atropine sulphate as the control groups. Besides, the in vitro effects of the extract (8 × 10−2–640 × 10−2 mg/ml) on the rabbit jejunum and guinea-pig ileum were evaluated. Results Phytochemical screening showed alkaloids, glycoside, saponins, tannins, triterpenes, flavonoids and steroids in the MEHA. The median lethal dose (LD50) of the MEHA after oral administration was approximately greater than 2000 mg/kg. The MEHA declined the diarrhoea onset and remarkably decreased the number of watery stools in the group that received 300 and 600 mg/kg. It also elicited a remarkable and non-dose-dependent reduction in the intestinal fluid volume. At 1000 mg/kg, the MEHA significantly inhibited the charcoal movement. In addition, the MEHA (8 × 10−2–640 × 10−2 mg/ml) elicited a remarkable decrease in the contractility of the rabbit jejunum over time and relaxed the guinea pig ileum. Besides, it showed concentration-dependent attenuation of the acetylcholine and histamine-induced contraction. Conclusion The extract under investigation revealed promising antidiarrhoeal properties that justified its traditional claim for use against diarrhoea.

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