scholarly journals Metabolism of myricetin and related compounds in the rat. Metabolite formation in vivo and by the intestinal microflora in vitro

1972 ◽  
Vol 130 (1) ◽  
pp. 141-151 ◽  
Author(s):  
L. A. Griffiths ◽  
G. E. Smith
Keyword(s):  
Oral Administration ◽  
Intestinal Microflora ◽  
Fission Products ◽  
Hydroxyl Groups ◽  
Dihydroxyphenylacetic Acid ◽  
Ring Fission ◽  
Hydroxyphenylacetic Acid ◽  
Micro Organisms

1. The metabolism of a group of polyphenols related in structure to myricetin (3,5,7,3′,4′,5′-hexahydroxyflavone), including myricetin, myricitrin, 3,4,5-trihydroxyphenylacetic acid, delphinidin, robinetin, tricetin, tricin, malvin and 5,7-dihydroxy-3′,4′,5′-trimethoxyflavone, has been studied both in vivo after oral administration to the rat and in vitro in cultures of micro-organisms derived from the intestine of the rat. 2. It was shown that the rat intestinal microflora are able to degrade compounds of this group to the ring-fission products observed in urine after oral administration of the specific flavonoid. 3. All flavones and flavonols possessing free 5- and 7-hydroxyl groups in the A ring and a free 4′-hydroxyl group in the B ring gave rise to ring-fission products that included 3′,5′-dihydroxyphenylacyl derivatives. 4. The metabolites 3,5-dihydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, 3,5-dihydroxyphenylpropionic acid and 3-hydroxyphenylpropionic acid were isolated and identified by chromatographic and spectral methods. 5. On anaerobic incubation in a thioglycollate medium it was shown that intestinal micro-organisms can effect cleavage of glycosidic bonds, ring fission of certain flavonoid molecules showing 3′,4′,5′-trihydroxyphenyl substitution and dehydroxylation of certain flavonoid metabolites. 6. The urinary excretion of the metabolites 3,5-dihydroxyphenylacetic acid and 3-hydroxyphenylacetic acid was completely abolished when neomycin-treated rats were used.

scholarly journals Metabolism of apigenin and related compounds in the rat. Metabolite formation in vivo and by the intestinal microflora in vitro

1972 ◽  
Vol 128 (4) ◽  
pp. 901-911 ◽  
Author(s):  
L. A. Griffiths ◽  
G. E. Smith
Keyword(s):  
Oral Administration ◽  
Intestinal Microflora ◽  
Biochanin A ◽  
Hydroxyl Group ◽  
Hydroxyl Groups ◽  
Flavonoid Compounds ◽  
Ring Fission ◽  
Micro Organisms

1. The metabolism of a group of flavonoid compounds related in structure to apigenin (4′,5,7-trihydroxyflavone) and including apigenin, apiin, naringin, phlorrhizin, acacetin, kaempferol, robinin, chrysin, tectochrysin and 4′,7-dihydroxyflavone, was studied both in vivo after oral administration to the rat, and in vitro in cultures of micro-organisms derived from the intestine of the rat. 2. The rat intestinal microflora is capable of effecting degradation of flavonoid compounds to metabolites observed in the urine after oral administration of the specific flavonoid. 3. All compounds possessing free 5- and 7-hydroxyl groups in the A ring and a free 4′-hydroxyl group in the B ring gave rise to ring-fission products, which included 4′-hydroxyphenylacyl derivatives. 4. On anaerobic incubation in a thioglycollate medium, intestinal micro-organisms can effect flavonoid-ring fission, cleavage of glycosidic bonds and the reduction of double bonds in the side chains of certain metabolites. 5. Two flavonoids (chrysin and tectochrysin) undergo hydroxylation in the 4′-position in vivo but not during incubation with the intestinal microflora in vitro. 6. Observations on the metabolism of other compounds substituted in the 4′-position, e.g. epiafzelechin, pelargonin and the isoflavones, genistein, biochanin A, daidzein and formononetin, by the intestinal microflora of the rat are also reported.

scholarly journals Osseointegrating and phase-oriented micro-arc-oxidized titanium dioxide bone implants

2021 ◽  
Vol 19 ◽  
pp. 228080002110068
Author(s):  
Hsien-Te Chen ◽  
Hsin-I Lin ◽  
Chi-Jen Chung ◽  
Chih-Hsin Tang ◽  
Ju-Liang He
Keyword(s):  
Titanium Dioxide ◽  
High Surface ◽  
Cell Activity ◽  
Active Surface ◽  
Rutile Phase ◽  
Hydroxyl Groups ◽  
Bone Implant ◽  
Implant System

Here, we present a bone implant system of phase-oriented titanium dioxide (TiO2) fabricated by the micro-arc oxidation method (MAO) on β-Ti to facilitate improved osseointegration. This (101) rutile-phase-dominant MAO TiO2 (R-TiO2) is biocompatible due to its high surface roughness, bone-mimetic structure, and preferential crystalline orientation. Furthermore, (101) R-TiO2 possesses active and abundant hydroxyl groups that play a significant role in enhancing hydroxyapatite formation and cell adhesion and promote cell activity leading to osseointegration. The implants had been elicited their favorable cellular behavior in vitro in the previous publications; in addition, they exhibit excellent shear strength and promote bone–implant contact, osteogenesis, and tissue formation in vivo. Hence, it can be concluded that this MAO R-TiO2 bone implant system provides a favorable active surface for efficient osseointegration and is suitable for clinical applications.

scholarly journals In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michele Dei Cas ◽  
Jessica Rizzo ◽  
Mariangela Scavone ◽  
Eti Femia ◽  
Gian Marco Podda ◽  
...  
Keyword(s):  
Oral Administration ◽  
Whole Blood ◽  
Serum Levels ◽  
Reversed Phase ◽  
Weekly Treatment ◽  
Low Dose Aspirin ◽  
Liquid Chromatography Tandem Mass ◽  
Enteric Coated

AbstractLow-dose aspirin (ASA) is used to prevent cardiovascular events. The most commonly used formulation is enteric-coated ASA (EC-ASA) that may be absorbed more slowly and less efficiently in some patients. To uncover these “non-responders” patients, the availability of proper analytical methods is pivotal in order to study the pharmacodynamics, the pharmacokinetics and the metabolic fate of ASA. We validated a high-throughput, isocratic reversed-phase, negative MRM, LC–MS/MS method useful for measuring circulating ASA and salicylic acid (SA) in blood and plasma. ASA-d4 and SA-d4 were used as internal standards. The method was applied to evaluate: (a) the "in vitro" ASA degradation by esterases in whole blood and plasma, as a function of time and concentration; (b) the "in vivo" kinetics of ASA and SA after 7 days of oral administration of EC-ASA or plain-ASA (100 mg) in healthy volunteers (three men and three women, 37–63 years). Parameters of esterases activity were Vmax 6.5 ± 1.9 and Km 147.5 ± 64.4 in plasma, and Vmax 108.1 ± 20.8 and Km 803.2 ± 170.7 in whole blood. After oral administration of the two formulations, tmax varied between 3 and 6 h for EC-ASA and between 0.5 and 1.0 h for plain-ASA. Higher between-subjects variability was seen after EC-ASA, and one subject had a delayed absorption over eight hours. Plasma AUC was 725.5 (89.8–1222) for EC-ASA, and 823.1(624–1196) ng h/mL (median, 25–75% CI) for plain ASA. After the weekly treatment, serum levels of TxB2 were very low (< 10 ng/mL at 24 h from the drug intake) in all the studied subjects, regardless of the formulation or the tmax. This method proved to be suitable for studies on aspirin responsiveness.

scholarly journals Evaluation of mutagenicity, genotoxicity and chronic toxicity of antiviral drug imidazolyl ethanamide pentandioic acid in in vitro and in vivo test systems

2021 ◽  
Vol 98 (5) ◽  
pp. 548-557
Author(s):  
E. A. Jain ◽  
D. Pleimes ◽  
A. A. Globenko
Keyword(s):  
Oral Administration ◽  
Chromosomal Aberrations ◽  
Ames Test ◽  
Chronic Toxicity ◽  
Micronucleus Test ◽  
Human Lymphocytes ◽  
Antiviral Drug ◽  
Systemic Exposure

Introduction. The antiviral properties of imidazolyl ethanamide pentandioic acid (IPA), the active compound of the drug product, has been proven in various experimental models. However, the literature data on the toxicological properties of IPA are limited.Purpose. To evaluate mutagenic and genotoxic properties in in vitro and in vivo models, as well as to study the toxicity of IPA following chronic oral administration to rats and dogs.Materials and methods. Mutagenic and genotoxic properties of IPA were assessed using the Ames test, the test of chromosomal aberrations in human lymphocytes, and the micronucleus test in rats. The chronic toxicity of IPA was studied in Sprague Dawley rats and beagle dogs of both sexes, to which IPA was administered orally at doses of 30-300 mg/kg/day for 26 and 39 weeks, respectively.Results and discussion. In the Ames test, the addition of IPA up to the maximum dose (5000 mcg/plate) did not result in the increase in the number of revertant colonies. At a concentration of up to 5000 mcg/ml, IPA did not cause chromosomal aberrations in human leukocytes. At doses doses ≤ 2000 mg/kg, IPA did not increase the amount of micronuclei in the bone marrow of rats. In chronic experiments, animals tolerated the administration of IPA well: the dose without an observed effect (NOEL) for rats and dogs was 300 mg/kg/day.Conclusion. IPA did not show mutagenic and genotoxic properties in standard in vitro and in vivo tests. With chronic oral administration to rats and dogs, NOEL IPA equal to 300 mg/kg/day provided a systemic exposure that was 8-10 and 41-65 times higher than that in humans, respectively. The results obtained allow us to consider the safety profile of the prolonged use in humans as favorable.

scholarly journals Design and Characterization of Combinational Domperidone-Famotidine Floating Drug Delivery System - In vitro and In vivo studies

2021 ◽  
Vol 62 (2) ◽  
pp. 144-162
Author(s):  
Mounika Chidurala ◽  
Raveendra Reddy J
Keyword(s):  
Drug Release ◽  
Oral Administration ◽  
Quality By Design ◽  
Release Kinetics ◽  
Cost Effective ◽  
Fickian Diffusion ◽  
In Vivo Studies ◽  
Pharmacokinetic Studies

Introduction: The drawbacks assosiated with oral administration of drugscan be controlled or minimized by gastro retentive formulations that remain buoyant within the stomach for an extended time by providing prolonged gastric retention and releasethe drug in an exceedingly extended manner thereby improving bioavailability. The current research was to develop and optimize Domperidone and Famotidine floating tablets with extended release by Quality by Design approach. Method: Based on QTPP (Quality Target Product Profile), CQAs (Critical Quality Attributes)wereidentified. Risk analysis by the evaluation of formulation and process parameters showed that optimizing the levels of polymers could reduce high risk to achieve the target profile. A 23factor experimental design with midpoints was selected for statistical analysis and optimization. Results: HPMC K100 and Carbopol 934P had a positive effect while ethyl cellulose demonstrated a negative effect on the selected responses. Drug release kinetics followed the first-order release with Higuchi diffusion and Fickian diffusion. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values. Abdominal X-ray imaging after oral administration of the tablets on a healthy rabbit’s stomach confirmed the extended floating behavior with shorter lag time. In vivo, pharmacokinetic studies in rabbits revealed that the optimized formulation exhibited prolonged drug release with enhanced Cmax, tmax, AUCo-t, and t1/2 of an optimized product when compared to the marketed product. Conclusions: It has been concluded that the application of Quality by Design in the formulation and optimization reduced the number of trials to produce a cost-effective formula.

scholarly journals Design and evaluation of a novel floating osmotic pump system

2009 ◽  
Vol 12 (1) ◽  
pp. 129 ◽  
Author(s):  
Zhihong Zhang ◽  
Bo Peng ◽  
Xinggang Yang ◽  
Chao Wang ◽  
Guangmei Sun ◽  
...  
Keyword(s):  
Drug Release ◽  
Oral Administration ◽  
In Vitro Release ◽  
Osmotic Pump ◽  
Matrix Tablets ◽  
In Vivo Evaluation ◽  
Pump System ◽  
Conventional Tablet

PURPOSE. Find a novel delivery system for oral administration of drugs that have absorption window in the upper part of gastrointestinal (GI) track. METHODS. Dipyridamole was chosen as the model drug. A novel system, which combined the osmotic pump controlled release system and the floating system, was designed; matrix tablets (MT) were prepared for compares. The effects of pH, temperature and hydrodynamic conditions on drug release and the floating behavior of floating osmotic pump system (FOP) were investigated. In vivo evaluation was performed by a three-crossover study in six Beagle dogs relative to the conventional tablet (CT). Cumulative percent input in vivo was compared with that of in vitro release profiles. RESULTS. Floating behavior of FOP, drug releases from FOP and MT were sensitive to pH of dissolution media but not sensitive to temperature; the release of dipyridamole from MT was influenced by stirring rate while drug release from FOP was not. AUC of FOP was larger than MT and CT. The linear correlations between fraction absorbed in vivo and fraction dissolved in vitro was established for FOP-a true zero-order release formula, whereas only a nonlinear correlation was obtained for MT. CONCLUTIONS. FOP could be a novel way for the oral administration for drugs like dipyridamole.

CYTOTOXICITY, ANTITUMOUR AND ANTICARCINOGENIC ACTIVITY OF CURCUMA LONGA ESSENTIAL OIL

INDIAN DRUGS ◽  
2014 ◽  
Vol 51 (03) ◽  
pp. 28-34
Author(s):  
V.B Liju ◽  
◽  
K Jeena ◽  
R. Kuttan
Keyword(s):  
Essential Oil ◽  
Oral Administration ◽  
Life Span ◽  
Cell Lines ◽  
Curcuma Longa ◽  
Cytochrome P450 Enzyme ◽  
Dalton’S Lymphoma ◽  
Dalton's Lymphoma

In the present study, we have evaluated the antitumour and anticarcinogenic activity of turmeric essential oil in vivo. Turmeric essential oil was found to have significant in vitro cytotoxic activity against Dalton’s lymphoma ascites cells (DLA) and Ehrlich ascites carcinoma (EAC) cancer cell lines. Concentration needed for 50% cytotoxicity (IC50) was 8 μg for DLA cells and 18 μg to EAC cell lines. Oral administration of turmeric essential oil was found to significantly increase the life span (56.25%) of Dalton’s Lymphoma Ascites (DLA) induced ascites tumour bearing mice as well as significantly reduced (P<0.001) the solid tumours. 3-Methyl cholanthrene induced sarcoma development was also delayed and there was significant increase in the life span of mice after oral administration of turmeric essential oil. Moreover, turmeric essential oil significantly (P<0.001) inhibited phenobarbitone induced cytochrome p450 enzyme activity in rats.

Anaerobes in ejaculates of subfertile men

1995 ◽  
Vol 1 (5) ◽  
pp. 462-478 ◽  
Author(s):  
Waltraud Eggert-Kruse ◽  
Gerhard Rohr ◽  
Wolfram Ströck ◽  
Susanne Pohl ◽  
Beate Schwalbach ◽  
...  
Keyword(s):  
Tract Infection ◽  
Genital Tract ◽  
Anaerobic Bacteria ◽  
Cervical Mucus ◽  
Anaerobic Growth ◽  
Pathogenic Species ◽  
Genital Tract Infection ◽  
Micro Organisms

Abstract The clinical significance of micro-organisms in semen samples of asymptomatic subfertile patients is a matter of constant debate. Usually little attention is paid to anaerobic bacteria as they are sensitive to transportation and culturing, and differentiation is difficult, costly and time-consuming. In the present study, special screening was carried out for anaerobes in ejaculates in addition to the routine microbial cultures of genital secretions of both partners. In addition to standard semen analysis and evaluation of sperm ability to penetrate cervical mucus (CM) in vivo (postcoital testing) and in vitro using a standardized test system, semen samples from 126 randomly chosen males of couples with a median duration of infertility of 4 years were examined for colonization with anaerobic bacteria. All couples were without clinical signs or symptoms of genital tract infection. The special care taken for anaerobic growth in semen samples gave a high rate of positive cultures and showed that nearly all ejaculates (99%) were colonized with anaerobic micro-organisms, and potentially pathogenic species were found in 71% of men. This rate was more than four times higher than that obtained with routine cultures and standard transportation (16%). Anaerobic bacterial growth of ≥106 colony forming units (CFU)/ml was seen in 42% (total range 103-108 CFU/ml). In addition, aerobic growth was found in 96%(≥106 CFU/ml in 21%), potentially pathogenic species in 61% of semen specimens. There were no marked differences in the prevalence of anaerobic micro-organisms in patients with reduced or normal sperm count, motility or morphology. Nor was there any significant difference in anaerobic colonization between samples with impaired or good ability to penetrate CM of female partners (in vivo or in vitro), or the CM of fertile donors in the in-vitro sperm-cervical mucus penetration test (SCMPT) in this asymptomatic group of patients. There was no clear association between microbial colonization and subsequent fertility in vivo within an observation period of 6 months. The results of this study suggest that anaerobic bacteria are often not detected when routine methods for microbial evaluation are used. This should be considered during assisted reproduction and in patients with symptoms of genital tract infection and should lead to further studies in infertile patients where subclinical infection or inflammation is indicated by specific markers in semen samples.

Polyphenols in Food: Cancer Prevention and Apoptosis Induction

2018 ◽  
Vol 25 (36) ◽  
pp. 4740-4757 ◽  
Author(s):  
Ashita Sharma ◽  
Mandeep Kaur ◽  
Jatinder Kaur Katnoria ◽  
Avinash Kaur Nagpal
Keyword(s):  
Cancer Prevention ◽  
Defense Mechanism ◽  
Antioxidant Property ◽  
The Body ◽  
Water Soluble ◽  
Stress Factors ◽  
In Vivo Studies ◽  
Hydroxyl Groups

Polyphenols are a group of water-soluble organic compounds, mainly of natural origin. The compounds having about 5-7 aromatic rings and more than 12 phenolic hydroxyl groups are classified as polyphenols. These are the antioxidants which protect the body from oxidative damage. In plants, they are the secondary metabolites produced as a defense mechanism against stress factors. Antioxidant property of polyphenols is suggested to provide protection against many diseases associated with reactive oxygen species (ROS), including cancer. Various studies carried out across the world have suggested that polyphenols can inhibit the tumor generation, induce apoptosis in cancer cells and interfere in progression of tumors. This group of wonder compounds is present in surplus in natural plants and food products. Intake of polyphenols through diet can scavenge ROS and thus can help in cancer prevention. The plant derived products can also be used along with conventional chemotherapy to enhance the chemopreventive effects. The present review focuses on various in vitro and in vivo studies carried out to assess the anti-carcinogenic potential of polyphenols present in our food. Also, the pathways involved in cancer chemopreventive effects of various subclasses (flavonoids, lignans, stilbenes and phenolic acids) of polyphenols are discussed.

scholarly journals A novel nucleoside rescue metabolic pathway may be responsible for therapeutic effect of orally administered cordycepin

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jong Bong Lee ◽  
Masar Radhi ◽  
Elena Cipolla ◽  
Raj D. Gandhi ◽  
Sarir Sarmad ◽  
...  
Keyword(s):  
Oral Administration ◽  
Metabolic Pathway ◽  
Oral Absorption ◽  
Therapeutic Effects ◽  
The Novel ◽  
Drug Candidates ◽  
Biopharmaceutical Properties

Abstract Although adenosine and its analogues have been assessed in the past as potential drug candidates due to the important role of adenosine in physiology, only little is known about their absorption following oral administration. In this work, we have studied the oral absorption and disposition pathways of cordycepin, an adenosine analogue. In vitro biopharmaceutical properties and in vivo oral absorption and disposition of cordycepin were assessed in rats. Despite the fact that numerous studies showed efficacy following oral dosing of cordycepin, we found that intact cordycepin was not absorbed following oral administration to rats. However, 3′-deoxyinosine, a metabolite of cordycepin previously considered to be inactive, was absorbed into the systemic blood circulation. Further investigation was performed to study the conversion of 3′-deoxyinosine to cordycepin 5′-triphosphate in vitro using macrophage-like RAW264.7 cells. It demonstrated that cordycepin 5′-triphosphate, the active metabolite of cordycepin, can be formed not only from cordycepin, but also from 3′-deoxyinosine. The novel nucleoside rescue metabolic pathway proposed in this study could be responsible for therapeutic effects of adenosine and other analogues of adenosine following oral administration. These findings may have importance in understanding the physiology and pathophysiology associated with adenosine, as well as drug discovery and development utilising adenosine analogues.

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