scholarly journals Gastrointestinal and Hepatotoxicity Assessment of an Anticancer Extract from Muricid Molluscs

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Chantel B. Westley ◽  
Kirsten Benkendorff ◽  
Cassandra M. McIver ◽  
Richard K. Le Leu ◽  
Catherine A. Abbott
Keyword(s):  
Hepatic Metabolism ◽  
Toxicity Assessment ◽  
The Body ◽  
Clinical Toxicity ◽  
The Family ◽  
First Pass ◽  
Medicinal Food ◽  
And Control ◽  
Pass Metabolism

Marine molluscs from the family Muricidae are under development as a potential medicinal food for the prevention of colon cancer and treatment of gynaecological cancers. Here we report the outcome of the firstin vivotoxicity assessment on an anticancer extract from a muricid mollusc containing brominated indole derivatives. Mice received the concentrated lipophilic extract by daily oral gavage over a two-week period. Mortality or clinical toxicity symptoms resulting from the extract were not detected during the trial, and there was no difference in the body weight of treated and control mice at the end of the trial. Histological analysis revealed some evidence for mild, idiosyncratic effects on the gastrointestinal tract and liver, including necrosis, fatty change, and inflammation in a small proportion (<40%) of mice. This is likely to result from first-pass hepatic metabolism of tyrindoxyl sulphate combined with second-pass metabolism of indoles. Overall however, oral administration of muricid extract containing brominated indoles does not result in severe clinical toxicity.

In-vivo evaluation of lipid lowering ability of Chloris paraguaiensis extracts

2020 ◽  
Vol 7 (2) ◽  
pp. 21-24
Author(s):  
Pavani C H
Keyword(s):  
Medicinal Plants ◽  
Chemical Constituents ◽  
The Body ◽  
Lipid Lowering ◽  
Medical Systems ◽  
In Vivo Evaluation ◽  
Standard Drug ◽  
Anti Oxidant ◽  
And Control

Hyperlipidemia is the immediate results of the excessive fat intake in food. This results in the elevated levels of cholesterol and triglycerides in the blood. This leads to heart conditions like CAD, hypertension, congestive heart failure as risk factors which can be lethal. There are many drugs to treat and control the lipids levels in the body. These drugs are either designed to prevent LDL accumulation and VLDL synthesis. Some drugs also lower the elevated levels of saturated lipids in the body. But many drugs are known to cause side effects and adverse effects; therefore, alternatives to the drugs are the subjects for current investigations. Herbs and medicinal plants are used as treatment sources for many years. They have been used in the Indian medical systems like Ayurveda, Siddha etc. As the application of herbs in the treatment is growing, there is an urgent need for the establishment of Pharmacological reasoning and standardization of the activity of the medicinal plants. Chloris paraguaiensis Steud. is Poyaceae member that is called locally as Uppugaddi. Traditionally it is used to treat Rheumatism, Diabetes, fever and diarrhoea. The chemical constituents are known to have anti-oxidant properties and most of the anti-oxidants have anti-hyperlipidemic activity too. Since the plant has abundant flavonoid and phenol content, the current research focusses on the investigation of the anti-hyperlipidemic activity of the plant Chloris extracts. Extracts of Chloris at 200mg/kg showed a comparably similar anti hyperlipidemia activity to that of the standard drug. The extracts showed a dose based increase in the activity at 100 and 200mg/kg body weight.

scholarly journals Clinical and in Vivo Response Following Surgery or Surgery Plus Adjuvant Chemotherapy or Immunotherapy for Colorectal Carcinoma in a Rat Model

1983 ◽  
Vol 76 (10) ◽  
pp. 833-840 ◽  
Author(s):  
A K House ◽  
M A L Maley
Keyword(s):  
Body Weight ◽  
Adjuvant Chemotherapy ◽  
Surgical Excision ◽  
The Body ◽  
Recurrent Tumour ◽  
Mesenteric Node ◽  
And Control ◽  
Tumour Weight

Two cohorts of rats, 240 with colon cancer and 150 controls, were assessed clinically and immunologically for their response to tumour and its management which was either by surgical excision alone or by surgical excision combined with either adjuvant chemotherapy or immunotherapy. The histology and invasion characteristics were observed for similarity with those of human lesions. Metastases were found in liver, lymph nodes, the peritoneum or lungs in 27% of animals during follow up. Significantly fewer adjuvant-treated rats had metastases than those receiving surgery alone ( P < 0.05), and less total tumour weight was found in the adjuvant-treated rats at four ( P < 0.03) and six ( P < 0.001) weeks postoperatively. Animals in the adjuvant immunotherapy group survived longer than in either other group ( P < 0.001). The crude parameters of host response to tumour, body, spleen and mesenteric lymph node weight were recorded and the latter two indexed to body weight. The body weight of tumour and control rats increased significantly with time ( P < 0.04). The spleen and mesenteric node indices were significantly ( P < 0.04) greater in tumour than control rats and were varied by recurrent tumour growth and by the adjuvant treatment administered postoperatively.

scholarly journals In Vivo Toxicity Assessment of Chitosan-Coated Lignin Nanoparticles in Embryonic Zebrafish (Danio rerio)

Nanomaterials ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 111
Author(s):  
Jared S. Stine ◽  
Bryan J. Harper ◽  
Cathryn G. Conner ◽  
Orlin D. Velev ◽  
Stacey L. Harper
Keyword(s):  
Antimicrobial Properties ◽  
Toxicity Assessment ◽  
Environmental Footprint ◽  
Control Groups ◽  
Charged Surfaces ◽  
Chorionic Membrane ◽  
High Concentrations ◽  
And Control ◽  
Oppositely Charged

Lignin is the second most abundant biopolymer on Earth after cellulose. Since lignin breaks down in the environment naturally, lignin nanoparticles may serve as biodegradable carriers of biocidal actives with minimal environmental footprint compared to conventional antimicrobial formulations. Here, a lignin nanoparticle (LNP) coated with chitosan was engineered. Previous studies show both lignin and chitosan to exhibit antimicrobial properties. Another study showed that adding a chitosan coating can improve the adsorption of LNPs to biological samples by electrostatic adherence to oppositely charged surfaces. Our objective was to determine if these engineered particles would elicit toxicological responses, utilizing embryonic zebrafish toxicity assays. Zebrafish were exposed to nanoparticles with an intact chorionic membrane and with the chorion enzymatically removed to allow for direct contact of particles with the developing embryo. Both mortality and sublethal endpoints were analyzed. Mortality rates were significantly greater for chitosan-coated LNPs (Ch-LNPs) compared to plain LNPs and control groups. Significant sublethal endpoints were observed in groups exposed to Ch-LNPs with chorionic membranes intact. Our study indicated that engineered Ch-LNP formulations at high concentrations were more toxic than plain LNPs. Further study is warranted to fully understand the mechanisms of Ch-LNP toxicity.

Resveratrol: nanocarrier-based delivery systems to enhance its therapeutic potential

Nanomedicine ◽  
2020 ◽  
Author(s):  
Gurinder Singh
Keyword(s):  
Water Solubility ◽  
Therapeutic Potential ◽  
Hepatic Metabolism ◽  
Enterohepatic Recirculation ◽  
Systemic Delivery ◽  
First Pass ◽  
High Doses ◽  
Sites Of Action

Resveratrol (3,5,4′-trihydroxystilbene) is a polyphenolic compound existing in trees, peanuts and grapes and exhibits a broad spectrum of promising therapeutic activities, but it is unclear whether this entity targets the sites of action after oral administration. In vivo applicability of resveratrol has limited success so far, mainly due to its incompetent systemic delivery resulting from its low water solubility, poor bioavailability and short biological half-life. First-pass metabolism and presence of enterohepatic recirculation create doubt on the biological application of high doses typically used for in vitro trials. To augment bioavailability, absorption and uptake of resveratrol by cellular internalization, countless approaches have been implemented which involve the use of nanocarriers. Nanocarriers are a well-known delivery system used to reduce first-pass hepatic metabolism, overcome enterohepatic recirculation and accelerate the absorption of drugs via lymphatic pathways.

scholarly journals Dried Leaf Artemisia Annua Improves Bioavailability of Artemisinin via Cytochrome P450 Inhibition and Enhances Artemisinin Efficacy Downstream

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 254 ◽  
Author(s):  
Matthew R. Desrosiers ◽  
Alexis Mittleman ◽  
Pamela J. Weathers
Keyword(s):  
Tissue Distribution ◽  
Artemisia Annua ◽  
Liver Microsomes ◽  
Hepatic Metabolism ◽  
Oral Consumption ◽  
Tnf Α ◽  
Ic50 Values ◽  
Distribution Studies ◽  
Pass Metabolism

Artemisia annua L. and artemisinin, have been used for millennia to treat malaria. We used human liver microsomes (HLM) and rats to compare hepatic metabolism, tissue distribution, and inflammation attenuation by dried leaves of A. annua (DLA) and pure artemisinin. For HLM assays, extracts, teas, and phytochemicals from DLA were tested and IC50 values for CYP2B6 and CYP3A4 were measured. For tissue distribution studies, artemisinin or DLA was orally delivered to rats, tissues harvested at 1 h, and blood, urine and feces over 8 h; all were analyzed for artemisinin and deoxyartemisinin by GC-MS. For inflammation, rats received an intraperitoneal injection of water or lipopolysaccharide (LPS) and 70 mg/kg oral artemisinin as pure drug or DLA. Serum was collected over 8 h and analyzed by ELISA for TNF-α, IL-6, and IL-10. DLA-delivered artemisinin distributed to tissues in higher concentrations in vivo, but elimination remained mostly unchanged. This seemed to be due to inhibition of first-pass metabolism by DLA phytochemicals, as demonstrated by HLM assays of DLA extracts, teas and phytochemicals. DLA was more effective than artemisinin in males at attenuating proinflammatory cytokine production; the data were less conclusive in females. These results suggest that the oral consumption of artemisinin as DLA enhances the bioavailability and anti-inflammatory potency of artemisinin.

scholarly journals Predicting Intestinal and Hepatic First-Pass Metabolism of Orally Administered Testosterone Undecanoate

2020 ◽  
Vol 10 (20) ◽  
pp. 7283 ◽  
Author(s):  
Atheer Zgair ◽  
Yousaf Dawood ◽  
Suhaib M. Ibrahem ◽  
Hyun-moon Back ◽  
Leonid Kagan ◽  
...  
Keyword(s):  
Liver Microsomes ◽  
Hepatic Metabolism ◽  
Hydrolysis Time ◽  
Testosterone Undecanoate ◽  
Main Site ◽  
Cell Homogenate ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

The bioavailability of orally administered drugs could be impacted by intestinal and hepatic first-pass metabolism. Testosterone undecanoate (TU), an orally administered ester prodrug of testosterone, is significantly subjected to first-pass metabolism. However, the individual contribution of intestinal and hepatic first-pass metabolism is not well determined. Therefore, the aim of the current study was to predict the metabolic contribution of each site. The hydrolysis–time profiles of TU incubation in human liver microsomes and Caco-2 cell homogenate were used to predict hepatic and intestinal first-pass metabolism, respectively. The in vitro half-life (t1/2 inv) for the hydrolysis of TU in microsomal mixtures was 28.31 ± 3.51 min. By applying the “well-stirred” model, the fraction of TU that could escape hepatic first-pass metabolism (FH) was predicted as 0.915 ± 0.009. The incubation of TU in Caco-2 cell homogenate yielded t1/2 inv of 109.28 ± 21.42 min, which was applied in a “Q gut” model to estimate the fraction of TU that would escape intestinal first-pass metabolism (FG) as 0.114 ± 0.02. Accordingly, only 11% of the absorbed fraction of TU could escape intestinal metabolism, while 91% can pass through hepatic metabolism. Hence, compared to the liver, the intestinal wall is the main site where TU is significantly metabolised during first-pass effect.

Direct Determination of the Body Content of Radionuclides: Abstract

2003 ◽  
Vol 3 (1) ◽  
pp. 9-9
Author(s):  
R. Griffith ◽  
H. Bergmann ◽  
F. A. Fry ◽  
D. Hickman ◽  
J.-L. Genicot ◽  
...  
Keyword(s):  
Direct Measurement ◽  
Direct Determination ◽  
The Body ◽  
Whole Body ◽  
Control Measurement ◽  
In Vivo Measurement ◽  
Calibration Methods ◽  
Partial Body ◽  
And Control

Previous ICRU reports have dealt with the formulation and properties of tissue substitutes and phantoms that are used to calibrate in vivo measurement systems. This report provides guidance on the overall process of the direct measurement of radionuclides in the human body for radiation protection and medical applications. It addresses the detectors and electronics used for the measurement; methods of background reduction and control; measurement geometries for whole body, partial body or organ counting; physical and mathematical calibration methods; data analysis; and quality assurance. It is directed to readers who need practical advice on the establishment and operation of direct measurement facilities.

In vivo leucine oxidation in the gastrointestinal tract of lambs infected with nematode parasite Trichostrongylus colubriformis

1999 ◽  
Vol 1999 ◽  
pp. 107-107
Author(s):  
Feng Yu ◽  
L.A. Bruce ◽  
R.L. Coop ◽  
F Jackson ◽  
J.C. MacRae
Keyword(s):  
Gastrointestinal Tract ◽  
Tracer Kinetics ◽  
Isotope Tracer ◽  
Major Consequence ◽  
Nematode Parasites ◽  
Arterial Blood ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

One major consequence of the presence of the nematode parasites in the gastrointestinal tract (GIT) of ruminants appears to be an elevated flow of endogenous N component from the small intestine, leading to adverse changes in host productivity (MacRae, 1993). However, many of these aspects have remained speculative because of a lack of appropriate methodology to quantify the influence of parasites on GIT protein metabolism. In the present study oxidation of leucine sequestrated from arterial blood and digesta-derived leucine during “first pass” metabolism in the GIT of lambs subjected to subclinical T. colubriformis infection were quantified directly, using trans-organ catheterisation procedures coupled with stable isotope tracer kinetics.

A Study of Changes in Whole-Body Calcium, Phosphorus, Sodium and Nitrogen by Neutron Activation Analysis in Vivo in Rats on a Calcium-Deficient Diet

1976 ◽  
Vol 51 (4) ◽  
pp. 399-402
Author(s):  
K. Boddy ◽  
R. Lindsay ◽  
I. Holloway ◽  
D. A. S. Smith ◽  
A. Elliott ◽  
...  
Keyword(s):  
Neutron Activation Analysis ◽  
Activation Analysis ◽  
The Body ◽  
Whole Body ◽  
Deficient Diet ◽  
Calcium Phosphorus ◽  
Dietary Period ◽  
Total Body ◽  
And Control

1. A method of measuring changes in the total body content of calcium, phosphorus, nitrogen and sodium in rats by activation analysis in vivo is described. 2. The change in the body content of the elements has been measured in rats on a calcium-deficient diet and in control animals, the body nitrogen being used to represent lean body mass for normalization. 3. There were significant differences in Ca/N and P/N but not in Ca/P ratios between the animals on a deficient diet and control animals at the end of the dietary period.

scholarly journals Ninety-Day Oral Toxicity Assessment of an Alternative Biopolymer for Controlled Release Drug Delivery Systems Obtained from Cassava Starch Acetate

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Douglas Rossi Jesus ◽  
Lorena Neris Barbosa ◽  
Thiago Bruno Lima Prando ◽  
Leonardo Franco Martins ◽  
Francielli Gasparotto ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Toxicity Assessment ◽  
Cassava Starch ◽  
Pharmaceutical Products ◽  
The Body ◽  
Oral Exposure ◽  
Oral Toxicity ◽  
Starch Acetate ◽  
Target Organs ◽  
And Control

The large consumption of biodegradable films from cassava starch acetate (FCSA) as ingredients in food and pharmaceutical products requires the assessment of the possible toxicity of these products. The aim of this study was to investigate the toxicity of biodegradable film from cassava starch acetate after oral exposure of Wistar rats for 90 days. The amount of food consumed and the body weight were weekly monitored. Blood and urine samples were obtained for the assessment of serum parameters and renal function. Histopathological analyses in target organs were also performed. No evidence of clinical toxicity in hematological, biochemical, or renal parameters in the FCSA-treated animals was found. In addition, relative organ weight and histopathological evaluations did not differ between groups treated with FCSA and control. Data obtained suggest that the subchronic exposure to FCSA does not cause obvious signs of toxicity in Wistar rats, indicating possible safety of this biofilm.

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