Distribution of mercury in subcellular fractions of brain, liver, and kidney after repeated oral administration of 203Hg-labeled methylmercuric chloride in mice

1981 ◽  
Vol 35 (3) ◽  
pp. 435-447 ◽  
Author(s):  
M. Mehra ◽  
B.H. Choi
Keyword(s):  
Oral Administration ◽  
Subcellular Fractions ◽  
Methylmercuric Chloride ◽  
Liver And Kidney

The effect of propylthiouracil and methimazole on the peripheral conversion of thyroxine to 3,5,3'-triiodothyronine in athyreotic thyroxine-maintained rats

1983 ◽  
Vol 103 (4) ◽  
pp. 509-520 ◽  
Author(s):  
J. van Doom ◽  
F. Roelfsema ◽  
D. van der Heide
Keyword(s):  
Cerebral Cortex ◽  
Oral Administration ◽  
Pituitary Gland ◽  
Subcellular Fractions ◽  
The Other ◽  
Nuclear Fraction ◽  
Relative Contribution ◽  
Liver And Kidney ◽  
Peripheral Conversion ◽  
The Brain

Abstract. The effect of prolonged oral administration of PTU and MMI on the local conversion of T4 to T3 was studied in T4-maintained athyreotic rats. For this purpose the rats were equilibrated with [125I]T4 and [131I]T3 by means of continuous iv infusions. PTU treatment reduced the MCR of both T4 and T3, as well as the T3 levels in plasma, muscle, liver, kidney and cerebellum. In the cerebral cortex the total intracellular T3 concentration was not affected, while in the pituitary it even increased. The amount of T3 derived from local conversion of T4 to T3 (LcT3(T4)) was reduced in the liver. PTU treatment did not influence Lc T3(T4) in the cerebellum, but did cause an increase in the amount of T3 derived from this source in the cerebral cortex and the pituitary gland (both the homogenate and the nuclear fraction). The results indicate that in contrast to that in liver, local T3 production in the brain and pituitary must occur predominantly via a pathway which is not inhibited by PTU. In MMI-treated rats the total T3 concentration in the cerebral cortex and cerebellum was not altered, whereas both the MCR of T3 and the T3 levels in plasma and various other tissues were elevated. The relative contribution of Lc T3(T4) increased in liver and was reduced in the cerebral cortex, cerebellum and pituitary gland. In all experiments in liver the contribution of Lc T3(T4) to nuclear T3 was negligible, whereas this was not the case for the other hepatic subcellular fractions. As in liver, virtually all renal nuclear T3 was derived from plasma. The present findings suggest that the production of T3 in liver and kidney, and its subsequent release into the blood, may provide a mechanism for the regulation of plasma T3 levels but is not a direct source of their nuclear T3. In the pituitary gland and the brain local T4 to T3 conversion functions as a source of T3 for the control of local utilization. In this respect the maintainance of constant T3 levels in the brain might be important. These differences among tissues suggest that different mechanisms are involved in T4 5'-deiodination.

Simultaneous Determination of Imatinib and N-Desmethyl Imatinib in Rat Plasma and Tissues Using LC-MS/MS

2019 ◽  
Vol 15 (2) ◽  
pp. 121-129
Author(s):  
Zhi Rao ◽  
Bo-xia Li ◽  
Yong-Wen Jin ◽  
Wen-Kou ◽  
Yan-rong Ma ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Oral Administration ◽  
Parent Drug ◽  
Gradient Elution ◽  
Biological Tissues ◽  
Rat Plasma ◽  
Running Water ◽  
Liver And Kidney ◽  
The Brain

Background: Imatinib (IM) is a chemotherapy medication metabolized by CYP3A4 to Ndesmethyl imatinib (NDI), which shows similar pharmacologic activity to the parent drug. Although methods for determination of IM and/or NDI have been developed extensively, only few observations have been addressed to simultaneously determine IM and NDI in biological tissues such as liver, kidney, heart, brain and bone marrow. Methods: A validated LC-MS/MS method was developed for the quantitative determination of imatinib (IM) and N-desmethyl imatinib (NDI) from rat plasma, bone marrow, brain, heart, liver and kidney. The plasma samples were prepared by protein precipitation, and then the separation of the analytes was achieved using an Agilent Zorbax Eclipse Plus C18 column (4.6 × 100 mm, 3.5 µm) with gradient elution running water (A) and methanol (B). Mass spectrometric detection was achieved by a triplequadrupole mass spectrometer equipped with an electrospray source interface in positive ionization mode. Results: This method was used to investigate the pharmacokinetics and the tissue distributions in rats following oral administration of 25 mg/kg of IM. The pharmacokinetic profiles suggested that IM and NDI are disappeared faster in rats than human, and the tissue distribution results showed that IM and NDI had good tissue penetration and distribution, except for the brain. This is the first report about the large penetrations of IM and NDI in rat bone marrow. Conclusion: The method demonstrated good sensitivity, accuracy, precision and recovery in assays of IM and NDI in rats. The described assay was successfully applied for the evaluation of pharmacokinetics and distribution in the brain, heart, liver, kidney and bone marrow of IM and NDI after a single oral administration of IM to rats.

Eudragit L-100 Capsules Aromatize and Quaternerize Chitosan for Insulin Nanoparticle Oral Delivery During Toxic Oxidative Stress in Rat Liver and Kidney

2020 ◽  
Vol 8 (3) ◽  
pp. 239-254 ◽  
Author(s):  
Reza Mahjub ◽  
Farzane K. Najafabadi ◽  
Narges Dehkhodaei ◽  
Nejat Kheiripour ◽  
Amir N. Ahmadabadi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oral Administration ◽  
Oral Delivery ◽  
Biochemical Parameters ◽  
Kidney Injury ◽  
Regular Insulin ◽  
Treated Group ◽  
Histopathological Change ◽  
Diabetic Rats ◽  
Liver And Kidney

Background: Insulin, like most peptides, is classified as a hydrophilic and macromolecular drug that is considered as a low permeable and unstable compound in the gastrointestinal (GI) tract. The acidic condition of the stomach can degrade insulin molecules. Moreover, the presence of proteolytic activities of some enzymes such as trypsin and chymotrypsin can hydrolyze amide-bonds between various amino-acids in the structures of peptides and proteins. However, due to its simplicity and high patient compliance, oral administration is the most preferred route of systemic drug delivery, and for the development of an oral delivery system, some obstacles in oral administration of peptides and proteins including low permeability and low stability of the proteins in GI should be overcome. Objective: In this study, the effects of orally insulin nanoparticles (INPs) prepared from quaternerized N-aryl derivatives of chitosan on the biochemical factors of the liver in diabetic rats were studied. Methods: INPs composed of methylated (amino benzyl) chitosan were prepared by the PEC method. Lyophilized INPs were filled in pre-clinical capsules, and the capsules were enteric-coated with Eudragit L100. Twenty Male Wistar rats were randomly divided into four groups: group1: normal control rats, group 2: diabetic rats, group 3: diabetic rats received capsules INPs(30 U/kg/day, orally), group 4: the diabetic rats received regular insulin (5 U/kg/day, subcutaneously). At the end of the treatment, serum, liver and kidney tissues were collected. Biochemical parameters in serum were measured using spectrophotometric methods. Also, oxidative stress was measured in plasma, liver and kidney. Histological studies were performed using H and E staining . Results: Biochemical parameters, and liver and kidney injury markers in serum of the diabetic rats that received INPs improved significantly compared with the diabetic group. INPs reduced oxidative toxic stress biomarkers in serum, liver and kidney of the diabetic treated group. Furthermore, a histopathological change was developed in the treated groups. Conclusion: Capsulated INPs can prevent diabetic liver and oxidative kidney damages (similar regular insulin). Therefore oral administration of INPs appears to be safe. Lay Summary: Although oral route is the most preferred route of administration, but oral delivery of peptides and proteins is still a challenging issue. Diabetes Mellitus may lead to severe complications, which most of them are life-threatening. In this study, we are testing the toxicity of oral insulin nanoparticles in kidney and liver of rats. For this investigation, we will prepare insulin nanoparticles composed of a quaternized derivative of chitosan. The nanoparticles will be administered orally to rats and the level of oxidative stress in their liver and kidney will be determined. The data will be compared to the subcutaneous injection of insulin.

scholarly journals LC-MS/MS analysis of doxycycline residues in chicken tissues after oral administration

2014 ◽  
Vol 58 (4) ◽  
pp. 573-579 ◽  
Author(s):  
Anna Gajda ◽  
Andrzej Posyniak ◽  
Grzegorz Tomczyk
Keyword(s):  
Oral Administration ◽  
Broiler Chickens ◽  
Thigh Muscle ◽  
Limit Of Quantification ◽  
Limit Values ◽  
Chicken Tissues ◽  
Short Period ◽  
Liquid Chromatography Tandem Mass ◽  
Liver And Kidney

Abstract For the purpose of quantitative determination of doxycycline (DC) residues in tissues, a sensitive liquid chromatography - tandem mass spectrometry (LC-MS/MS) method was developed. The method was used to determine DC residues in chicken tissues (breast and thigh muscle, liver and kidney) after oral administration with drinking water to five-weak-old broiler chickens. The DC was administered for five consecutive days at a therapeutic dose of 10 mg/kg b.w. once a day. The tissues were collected after 6 h, 24 h, 7 d, and 8 d. The method was validated and the decision limit was established for muscle - 109.2 μg/kg, for liver - 326.1 μg/kg, and for kidney - 634.0 μg/kg. The detection limit was 2 μg/kg and the limit of quantification was 5 μg/kg. In a short period after ceasing the treatment, the detected concentrations of DC were much higher than the established maximum residue limit values. The highest residue concentrations of DC were observed in the kidney, followed by the liver and muscle. The lowest concentration of DC was determined in tight muscle.

An in vitro study on metabolism of 17β-boldenone and boldione using cattle liver and kidney subcellular fractions

2007 ◽  
Vol 586 (1-2) ◽  
pp. 177-183 ◽  
Author(s):  
R. Merlanti ◽  
G. Gallina ◽  
F. Capolongo ◽  
L. Contiero ◽  
G. Biancotto ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Subcellular Fractions ◽  
Vitro Study ◽  
Liver And Kidney

EVALUATION OF AMOXICILLIN WITHDRAWAL PERIOD TIME IN POMPANO LIVER AND KIDNEY

2015 ◽  
Vol 41 (03) ◽  
pp. 213-218
Author(s):  
Chia-Yih Wang ◽  
Shi-Yuan Sheu ◽  
Yi-Chih Lei ◽  
Jiann-Hsiung Wang ◽  
Ming-Huang Chang ◽  
...  
Keyword(s):  
Single Dose ◽  
Oral Dose ◽  
Oral Administration ◽  
Mobile Phase ◽  
Bacterial Infections ◽  
Withdrawal Period ◽  
Oral Gavage ◽  
Fluorescence Detector ◽  
Daily Dose ◽  
Liver And Kidney

Amoxicillin is an antibiotic which belongs to the group of penicillins. It is approved in Taiwan for treating bacterial infections caused by Streptococcus sp. and Photobacterium sp. in anguilliformes, perciformes and salmoniformes. The pharmacokinetics of amoxicillin were determined in pompano following oral administration of a single dose of 40 mg/kg. Residue studies were performed to determine residues in liver and kidney tissues of healthy fish after oral gavage of amoxicillin at a daily dose of 40 mg/kg for five consecutive days. Amoxicillin residues were analyzed by HPLC using Hypersil-100 C18 column (150 mm × 4.6 mm i.d.) and mobile phase consists of 10 mM K2HPO4(pH 8.5) with acetonitrile (80:20, v/v), at a flow rate of 1 mL/min. The effluent was monitored using a fluorescence detector set as 358 and 440 nm as excitation and emission wavelengths. Following a single oral dose, amoxicillin residues in 0.5 h post-dosing pompano were at a maximum of 6.17 μg/g in liver and 4.27 μg/g in kidney; the concentration of amoxicillin in liver and kidney declined with half-lives of 18.3 and 12.0 h. Amoxicillin residues in pompano liver and kidney tissues were proved to be under the MRL, 0.5 ug/g (liver and kidney) after a withdrawal period of five days.

scholarly journals The protective role of propolis against multi heavy metals-induced oxidative stress-hepato-renal damage in the male of albino rats

2021 ◽  
Author(s):  
Ayman Ahmed Bassiouny El-Amawy ◽  
Samir Attia Mohammed Zaahkouk ◽  
Hesham Gamal Abdel Rasheed ◽  
Bassem Elsayed Elaraby Mohammed
Keyword(s):  
Heavy Metals ◽  
Oral Administration ◽  
Antioxidant Defense System ◽  
Protective Role ◽  
Albino Rats ◽  
Protective Effects ◽  
Toxic Heavy Metals ◽  
Propolis Extract ◽  
Liver And Kidney

Abstract The study was designed to clarify the hepato-renal protective effects of propolis extract against heavy metals-induced toxicity via oral administration to the males of albino rats. Lead (Pb), Nickel (Ni), Cadmium (Cd), and Antimony (Sb) are toxic heavy metals have the ability to produce reactive radicals in the biological systems causing public and animals health hazards through disrupting balances between pro-oxidant and antioxidant defense system, resulting in excessive reactive oxygen species (ROS) production. The most commonly affected organs are liver and kidney. Propolis is a natural product with different shapes and resinous substance collected by honey bees, it attenuates many diseases damage due to its anti-oxidative action and its potentiality to minimize the deleterious effects of free radicals on tissues. The concentrations of Pb, Cd, Ni and Sb as well as the activities of antioxidants endogenous enzymes including; glutathione peroxidase (Gpx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD) were all determined in the tissues of liver and kidney; while aspartate transaminase (ASAT), alanine transaminase (ALAT), total protein (TP), urea and createnine, were measured in the serum of experimental rats beside histopathologicl examination in the tissues of liver and kidney. The oral administration of propolis provided a significantly therapeutic role against multi-metals-induced hepato-renal toxicity with relative improving to histopathological changes because of its scavenging and chelating properties as concluded from the present investigation.

scholarly journals In vitro Antioxidant and In vivo Hepatocurative and Nephrocurative Activities of Aqueous Leaf Extract of Newbouldia laevis in Albino Rats

2021 ◽  
pp. 114-125
Author(s):  
Mohammed A. Sulaiman ◽  
Mahmoud S. Jada ◽  
Augustine Elizabeth ◽  
Abubakar Umar Modibbo
Keyword(s):  
Oral Administration ◽  
Leaf Extract ◽  
Kidney Diseases ◽  
Albino Rats ◽  
Protein Levels ◽  
Ameliorative Effect ◽  
Liver And Kidney ◽  
Aqueous Leaf Extract

The in vitro antioxidant activity and in vivo hepatocurative and nephrocurative potential of Newbouldia laevis aqueous leaf extract (NLALE) was evaluated. The study used 30 male, albino rats (Rattus norvegicus) weighing 180 ± 20 g, of which 25 were intoxicated by oral administration of a single dose of diclofenac (100 mg/kg b. wt.). Animals were treated by oral administration of silymarin (200 mg/kg b. wt.), furosemide (1.5 mg/kg b. wt.) and NLALE (200 mg/kg and 400 mg/kg b. wt.) for seven consecutive days before animals were sacrificed on the 8th day and serum/plasma was analyzed for biochemical markers of hepatotoxicity and nephrotoxicity. Phytochemical screening of NLALE revealed the presence of alkaloids, flavonoids, glycosides, phenols, saponins, steroids and tannins. The extract scavenged DPPH radical, reduced Fe3+ and inhibited TBARs in comparable manner to ascorbic acid in vitro. NLALE also attenuated diclofenac-induced liver and kidney intoxication as indicated by the significantly (p<0.05) reduced levels of serum biomarkers of hepatotoxicity: ALT, AST, bilirubin, but increased total protein levels and nephrotoxicity: urea, creatinine, Na+ and K+. The observed effects are dose dependent as the 400 mg/kg b. wt. appeared to be more potent than the 200 mg/kg b. wt. dose. It may be concluded from this study that Newbouldia laevis leaf has ameliorative effect against diclofenac-induced hepatotoxicity and nephrotoxicity probably through antioxidative mechanism and the curative claim and the folkloric use of the plant in the treatment of liver and kidney diseases have been scientifically validated

scholarly journals Oral bioavailability of ATP after prolonged administration

2010 ◽  
Vol 105 (3) ◽  
pp. 357-366 ◽  
Author(s):  
Erik J. C. M. Coolen ◽  
Ilja C. W. Arts ◽  
Otto Bekers ◽  
Chris Vervaet ◽  
Aalt Bast ◽  
...  
Keyword(s):  
Uric Acid ◽  
Oral Administration ◽  
Healthy Subjects ◽  
Animal Studies ◽  
Purinergic Receptors ◽  
Daily Intake ◽  
Prolonged Administration ◽  
Liver And Kidney ◽  
Enteric Coated ◽  
To Receive

Purinergic receptors are important for the regulation of inflammation, muscle contraction, neurotransmission and nociception. Extracellular ATP and its metabolites are the main ligands for these receptors. Occasional reports on beneficial results of ATP administration in human and animal studies have suggested the bioavailability of oral ATP supplements. We investigated whether prolonged daily intake of oral ATP is indeed bioavailable. Thirty-two healthy subjects were randomised to receive 0, 250, 1250 or 5000 mg ATP per d for 28 d by means of enteric-coated pellets. In addition, on days 0 and 28, all thirty-two subjects received 5000 mg ATP to determine whether prolonged administration would induce adaptations in the bioavailability of ATP. ATP supplementation for 4 weeks did not lead to changes in blood or plasma ATP concentrations. Of all ATP metabolites, only plasma uric acid levels increased significantly after the administration of 5000 mg of ATP. Prolonged administration of ATP was safe as evidenced from liver and kidney parameters. We conclude that oral administration of ATP only resulted in increased uric acid concentrations. On the basis of these findings, we seriously question the claimed efficacy of oral ATP at dosages even lower than that used in the present study.

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