Disposition and metabolism of Ethylene glycol 2-ethylhexyl ether in Sprague Dawley rats, B6C3F1/N mice, and in vitro in rat hepatocytes

The toxicity of allyl alcohol and several glycols (ethylene glycol, 1,2-propanediol, 1,3-propanediol, methoxyethanol, and the glycol ether dioxane) was studied in cultures of 3T3 cells and in co-cultures of 3T3 cells with microcarrier-attached hepatocytes. Metabolism-mediated effects on the cytotoxicity to 3T3 cells were recorded by differences in the growth of the cultures exposed in the presence or absence of hepatocytes. Hepatocyte viability was determined by depletion of intracellular lactate dehydrogenase and effects on the biotransformation ability of hepatocytes were assessed by determination of O-deethylation of 7-ethoxycoumarin (EOD activity). Allyl alcohol was the only substance more toxic to the hepatocytes than to 3T3 cells cultured in the absence of hepatocytes. Toxicity to 3T3 cells of allyl alcohol, ethylene glycol, and 1,3-propanediol, but not of 1,2-propanediol, methoxyethanol and dioxane, was markedly enhanced when the cells were co-cultured with hepatocytes. The results indicate that the toxicity of allyl alcohol, ethylene glycol, and 1,3-propanediol, to 3T3 cells depends on the formation of active metabolites. For ethylene glycol and 1,3-propanediol, growth of 3T3 cells in co-cultures was reduced at concentrations without effects on hepatocyte viability. Co-culture of 3T3 cells with microcarrier-attached rat hepatocytes represents a suitable approach for the in vitro evaluation of metabolism-mediated cytotoxicity.

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Pharmacological comparison of four biopolymeric natural gums as hemostatic agents for management of bleeding wounds: preliminary in vitro and in vivo results

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-021-00237-z ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Himanshu Kushwah ◽

Nidhi Sandal ◽

Meenakshi Chauhan ◽

Gaurav Mittal

Keyword(s):

Xanthan Gum ◽

Guar Gum ◽

Human Lymphocytes ◽

Sprague Dawley ◽

Gum Tragacanth ◽

Civilian Trauma ◽

Sprague Dawley Rats ◽

Cytotoxicity Studies

Abstract Background Uncontrolled bleeding is one of the primary reasons for preventable death in both civilian trauma and military battle field. This study evaluates in vitro and in vivo hemostatic potential of four biopolymeric natural gums, namely, gum tragacanth, guar gum, xanthan gum, and gum acacia. In vitro evaluation of whole blood clotting time and erythrocyte agglutination assay were carried out. In vitro cytotoxicity studies with respect to each gum were done in human lymphocytes to ascertain percent cell viability. In vivo hemostatic potential of each gum (as sponge dressing and powder form) was evaluated in Sprague Dawley rats using tail bleeding assay and compared with commercially available hemostatic sponge. Other important parameters like (a) time taken for complete hemostasis, (b) amount of blood absorbed, (c) adherence strength of developed hemostatic dressing(s), (d) incidence of re-bleeding, and (e) survival of animals were also studied. Results Of the four test gums studied, xanthan gum (@3mg/ml of blood) and gum tragacanth (@35mg/ml of blood) were able to clot blood in least time (58.75±6.408 s and 59.00±2.082 s, respectively) and exhibited very good hemostatic potential in vitro. Except for xanthan gum, all other test gums did not exhibit any significant cytotoxicity at different time points till 24 h. In rat tail bleeding experiments, gum tragacanth sponge dressing and powder achieved hemostasis in least time (156.2±12.86 s and 76±12.55 s, respectively) and much earlier than commercially available product (333.3±38.84 s; p˂0.01). Conclusion Results indicate potential of gum tragacanth to be developed into a suitable hemostatic product.

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Bioavailability in Vivo of Benzo[a]Pyrene Adsorbed to Diesel Particulate

Toxicology and Industrial Health ◽

10.1177/074823379100700302 ◽

1991 ◽

Vol 7 (3) ◽

pp. 125-139 ◽

Cited By ~ 6

Author(s):

David R. Bevan ◽

David M. Ruggio

Keyword(s):

Health Risks ◽

Quantitative Description ◽

Intratracheal Instillation ◽

Direct Analysis ◽

Sprague Dawley ◽

Reasonable Estimate ◽

Diesel Particulate ◽

Sprague Dawley Rats

To evaluate health risks associated with exposure to particulates in the environment, it is necessary to quantify the bioavailability of carcinogens associated with the particulates. Direct analysis of bioavailability in vivo is most readily accomplished by adsorbing a radiolabeled form of the carcinogen to the particulate. A sam ple of native diesel particulate collected from an Oldsmobile die sel engine that contained 1.03 μ g benzo[ a] pyrene ( BaP)/ g particulate was supplemented with exogenous [ 3 H]- BaP to pro duce a particulate containing 2.62 μ g BaP/g. To insure that elu tion of BaP from native and [3 H] -BaP-supplemented particulate was similar, in vitro analyses were performed. When using phos pholipid vesicles composed of dimyristoylphosphatidylcholine (DMPC), 1.52% of total BaP was eluted from native particulate into the vesicles in 18 hrs; from [ 3 H] -BaP supplemented particu late, 1.68% was eluted. Using toluene as eluent, 2.55% was eluted from native particulate, and 8.25% from supplemented particulate, in 6 hrs. Supplemented particulate was then instilled intratracheally into male Sprague-Dawley rats and distribution of radioactivity was analyzed at selected times over 3 days. About 50% of radioactivity remained in lungs at 3 days following instil lation, with 30% being excreted into feces and the remainder dis tributed throughout the organs of the rats. To estimate the amount of radioactivity that entered feces through swallowing of a portion of the instilled dose, [3 H] -BaP-supplemented particu late was instilled intratracheally into rats that had a cannula sur gically implanted in the bile duct. Rate of elimination of radio activity into bile was monitored; 10.6% of radioactivity was re covered in 6 hr, an amount slightly lower than the 12.8% ex creted in 6 hrs into feces of animals with intact bile ducts. Our studies provide a quantitative description of the distribution of BaP and its metabolites following intratracheal instillation of diesel particulate. Because rates of elution of BaP in vitro are similar for native diesel particulate and particulate with supple mental [ 3H] -BaP, our results provide a reasonable estimate of the bioavailability in vivo of BaP associated with diesel particu late.

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Safety Assessment of a Hydroethanolic Extract of Caralluma fimbriata

International Journal of Toxicology ◽

10.1177/1091581813492827 ◽

2013 ◽

Vol 32 (5) ◽

pp. 385-394 ◽

Cited By ~ 3

Author(s):

Antoinette Y. Odendaal ◽

Narendra S. Deshmukh ◽

Tennille K. Marx ◽

Alexander G. Schauss ◽

John R. Endres ◽

...

Keyword(s):

Developmental Toxicity ◽

Toxicity Study ◽

Developmental Study ◽

Sprague Dawley ◽

Oral Toxicity ◽

Toxicological Assessment ◽

Sprague Dawley Rats ◽

Chromosomal Aberration Test ◽

Hydroethanolic Extract

This toxicological assessment evaluated the safety of a hydroethanolic extract prepared from Caralluma fimbriata (CFE), a dietary supplement marketed worldwide as an appetite suppressant. Studies included 2 in vitro genotoxicity assays, a repeated dose oral toxicity study, and a developmental study in rats. No evidence of in vitro mutagenicity or clastogenicity surfaced in the in vitro studies at concentrations up to 5000 μg of extract/plate (Ames test) or 5000 μg of extract/mL (chromosomal aberration test). No deaths or treatment-related toxicity were seen in the 6-month chronic oral toxicity study in Sprague-Dawley rats conducted at 3 doses (100, 300, and 1000 mg/kg body weight (bw)/d). The no observed effect level for CFE in this study was considered to be 1000 mg/kg bw/d. A prenatal developmental toxicity study conducted at 3 doses (250, 500, and 1000 mg/kg bw/d) in female Sprague-Dawley rats resulted in no treatment-related external, visceral, or skeletal fetal abnormalities, and no treatment-related maternal or pregnancy alterations were seen at and up to the maximum dose tested. CFE was not associated with any toxicity or adverse events.

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Metabolism of triallate in Sprague-Dawley rats. 3. In vitro metabolic pathways

Journal of Agricultural and Food Chemistry ◽

10.1021/jf00025a030 ◽

1993 ◽

Vol 41 (1) ◽

pp. 141-147 ◽

Cited By ~ 6

Author(s):

Amy G. Hackett ◽

John J. Kotyk ◽

Hideji. Fujiwara ◽

Eugene W. Logusch

Keyword(s):

Metabolic Pathways ◽

Sprague Dawley ◽

Sprague Dawley Rats

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TRANSFERSOME GEL FORMULATION OF AN ETHANOL EXTRACT OF APPLES (MALUS DOMESTICA MILL) CONTAINING ANTIOXIDANTS AND IN VITRO PENETRATION TESTING USING FRANZ DIFFUSION CELLS

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2017.v9s1.19_24 ◽

2017 ◽

Vol 9 ◽

pp. 32 ◽

Cited By ~ 1

Author(s):

Nurarita Fadila Zesiorani ◽

Effionora Anwar

Keyword(s):

Ethanol Extract ◽

Sprague Dawley ◽

Diffusion Cells ◽

Sprague Dawley Rats ◽

Apple Peel ◽

Franz Diffusion Cells ◽

Drug Efficiency ◽

And Control ◽

Peel Extract

Objective: This study aims to formulate and characterize a transfersome apple peel extract, formulate it into a gel, and compare it with a control gelmade without transfersome.Methods: Both gels were evaluated, stability tested, and penetration tested using Franz diffusion cells on the skin of female Sprague-Dawley rats. Thetransfersome preparations were formulated with different concentrations of the active substance, quercetin: 0.5% (F1); 0.7% (F2), and 1.0% (F3).Results: Based on the characterization results, F1 was selected as the optimum gel formulation because it had spherical morphology, a Dmean volume of106.44±2.70 nm, a polydispersity index of 0.078±0.01, a zeta potential of −49.96±2.05 mV, and a drug efficiency entrapment percentage of 78.78±0.46%.The cumulative amount of quercetin that was penetrated with the transfersome gel was 1514.41±26.31 μg/cm2, whereas the penetration with thecontrol gel extract was 1133.62±18.96 μg/cm2. The cumulative percentages of the penetrated gel transfersome and gel extract were 78.40±1.89%and 49.89±0.88%, respectively. The fluxes of transfersome gel and control gel extract were 52.33±0.11 μg/cm²/hrs and 40.89±0.68 μg/cm²/hrs,respectively.Conclusions: Based on these results, it can be concluded that the gel with transfersome exhibited better penetration than the gel extract alone.

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Effects of androgens on bioactivity and immunoreactivity of pituitary FSH in GnRH antagonist-treated male rats

Acta Endocrinologica ◽

10.1530/acta.0.1220168 ◽

1990 ◽

Vol 122 (2) ◽

pp. 168-174 ◽

Cited By ~ 12

Author(s):

Om P. Sharma ◽

Shafiq A. Khan ◽

Gerhard F. Weinbauer ◽

Mohammed Arslan ◽

Eberhard Nieschlag

Keyword(s):

Isoelectric Focusing ◽

Gnrh Antagonist ◽

Molecular Composition ◽

Male Rats ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Combined Administration ◽

Ph Range ◽

Fsh Bioactivity

Abstract The effects of androgens on the bioactivity and molecular composition of pituitary FSH were examined in intact and GnRH antagonist-suppressed male rats. Eight groups of adult Sprague-Dawley rats were subjected to the following treatments: antagonist (75 μg/day by osmotic minipumps; sc), testosterone-filled Silastic implants (3×5 cm, sc), dihydrotestosterone-filled Silastic implants (3×5 cm, sc), E2 benzoate (15 μg/day, sc), and combined administration of antagonist with either steroid for 3 weeks. At the end of the treatment period, pituitaries were dissected out and homogenised. FSH content was determined in the pituitary extracts by an in vitro bioassay and a radioimmunoassay. Individual pituitary extracts from rats treated with vehicle, testosterone and testosterone + antagonist were subjected to isoelectric-focusing on sucrose density gradients performed in the pH range from 3.5 to 7.0. Individual isoelectric-focusing fractions (100-120) were analysed for bioactive and immunoreactive FSH. Treatment with antagonist, E2 or antagonist + E2 caused a significant decrease in pituitary FSH, whereas testosterone and dihydrotesterone alone or in combination with antagonist prevented the decrease in pituitary FSH. The effects of all treatments on both bioactive and immunoreactive FSH were similar. Testosterone treatment not only maintained FSH synthesis but also altered the molecular composition of pituitary FSH. Following treatment with testosterone there was a shift of maximal FSH bioactivity to the more acidic pH range. On the other hand, less bioactivity was recovered than corresponding immunoreactivity in the higher pH region, resulting in significantly reduced ratios of bioactivity to immunoreactivity of FSH. No significant differences were found in the isoelectric-focusing profiles or bioactivity to immunoreactivity ratios of pituitary FSH in animals treated with testosterone alone or in combination with antagonist. The results demonstrate that testosterone not only maintained the synthesis of both bioactive and immunoreactive FSH in male rats, but also influences the molecular composition of pituitary FSH. These effects of testosterone on pituitary FSH appear not to be mediated through hypothalamic GnRH.

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THE EFFECT OF STILBOESTROL ANALOGUES ON THE METABOLISM OF STEROIDS BY THE TESTIS AND PROSTATE OF THE RAT IN VITRO

Journal of Endocrinology ◽

10.1677/joe.0.0590539 ◽

1973 ◽

Vol 59 (3) ◽

pp. 539-544 ◽

Cited By ~ 9

Author(s):

VARAPAN DANUTRA ◽

MAUREEN E. HARPER ◽

K. GRIFFITHS

Keyword(s):

Marked Effect ◽

Enzyme System ◽

Testicular Tissue ◽

Sesame Oil ◽

Prostatic Tissue ◽

Synthetic Activity ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Testosterone Administration

SUMMARY Male Sprague—Dawley rats were injected (i.m.) daily for 10 days with 100 μg of either oestradiol-17β, diethylstilboestrol (DES), dl-dihydrodibutylstilboestrol (dl-DHBS) or meso-dihydrodibutylstilboestrol (meso-DHBS) in 0·2 ml sesame oil. After 10 days, the testicular tissue was removed and incubated simultaneously with [7α-3H]dehydroepiandrosterone and [4-14C]17α-hydroxyprogesterone. Less testosterone was synthesized by the testicular tissue from animals treated with oestradiol-17β, DES and meso-DHBS than by the controls or animals treated with dl-DHBS. The decreased synthetic activity was related to the decreased activity of both the 17β-hydroxysteroid dehydrogenase and 17α-pregnene-C17, 20-lyase enzyme systems. Prostatic tissue was also incubated with [7α-3H]testosterone. Administration of DES, oestradiol-17β or meso-DHBS increased the metabolism of testosterone by the prostatic tissue with a marked effect on the 5α-reductase enzyme system.

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Regulation of mdrlb gene expression in Fischer, Wistar and Sprague-Dawley rats in vivo and in vitro

Carcinogenesis ◽

10.1093/carcin/17.3.451 ◽

1996 ◽

Vol 17 (3) ◽

pp. 451-457 ◽

Cited By ~ 19

Author(s):

Barbara A. Hill ◽

Paul C. Brown ◽

Karl-Heinz Preisegger ◽

Jeffrey A. Silverman

Keyword(s):

Gene Expression ◽

Sprague Dawley ◽

Sprague Dawley Rats

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