scholarly journals Monitoring the Level of 14C-Labelled Selegiline Following Oral Administration

2017 ◽  
Vol 11 (1) ◽  
pp. 1-8
Author(s):  
Huba Kalász ◽  
Kornélia Tekes ◽  
Erzsébet B. Faigl ◽  
Zita Pöstényi ◽  
Eszter Berekméri ◽  
...  
Keyword(s):  
Serum Level ◽  
Oral Administration ◽  
Time Dependence ◽  
Tissue Distribution ◽  
Intraperitoneal Injection ◽  
Intraperitoneal Administration ◽  
Reversed Phase ◽  
Reversed Phase Hplc ◽  
Body Compartments ◽  
The Brain

Background: Selegiline [(-)-deprenyl] is widely used for the treatment of Parkinson’s disease in humans. Objective: Time-dependence of tissue distribution of selegiline following per os administration to rats. Method: Oral administration of radiolabeled selegiline to rats resulted in a pattern of tissue distribution similar to that following intraperitoneal injection. Analyses were done using both reversed-phase HPLC and also by counting radioactivity in various body compartments of rats. Results: As a consequence of oral administration of 30 mg/kg of selegiline, its level in the stomach was extremely high (179.57 µg/g tissue through 54.67 µg/g at 15 min to 120 min), that is one magnitude higher than that in the serum level. High selegiline concentrations were also detected in the lacrimal glands (7.45 µg/g), kidneys (6.87 µg/g), livers (6.01 µg/g) and lungs (3.47 µg/g) after 30 minutes of application, which were higher than after intraperitoneal injections. Conclusion: The relatively high tissue levels remained for 120 min monitoring. Selegiline levels in the brain (1.69 µg/g) and in the testes (1.88 µg/g) were also considerably higher than following intraperitoneal administration during the entire period of observation (15 to 120 min).

scholarly journals Novel fish hypothalamic neuropeptides stimulate the release of gonadotrophins and growth hormone from the pituitary of sockeye salmon

2006 ◽  
Vol 188 (3) ◽  
pp. 417-423 ◽  
Author(s):  
Masafumi Amano ◽  
Shunsuke Moriyama ◽  
Masayuki Iigo ◽  
Shoji Kitamura ◽  
Noriko Amiya ◽  
...  
Keyword(s):  
Anterior Pituitary ◽  
Sockeye Salmon ◽  
Brain Regions ◽  
Pituitary Hormones ◽  
Reversed Phase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pituitary Cells ◽  
Reversed Phase Hplc ◽  
Hypothalamic Neuropeptides ◽  
The Brain

We recently identified a cDNA encoding three novel fish hypothalamic neuropeptides, having LPXRF-NH2 from the goldfish brain. In this study, to clarify the physiological functions of these three LPXRFamide peptides (gfLPXRFa-1, -2, and -3), we analysed the localisation and hypophysiotrophic activity of these peptides using sockeye salmon, Oncorhynchus nerka, in which immunoassay systems for several anterior pituitary hormones have been developed. gfLPXRFa-immunoreactive cell bodies were detected in the nucleus posterioris periventricularis of the hypothalamus and immunoreactive fibres were distributed in various brain regions and the pituitary. We also detected gfLPXRFa-immunoreactivity in the pituitary by competitive enzyme-linked immunosorbent assay combined with reversed-phase HPLC. These three gfLPXRFamide peptides stimulated the release of FSH, LH and GH, but did not affect the release of prolactin (PRL) and somatolactin (SL) from cultured pituitary cells. These results suggest that novel fish hypothalamic LPXR-Famide peptides exist in the brain and pituitary of sockeye salmon and stimulate the release of gonadotrophins and GH from the pituitary.

scholarly journals Effect of blockade of synthesis of nitric oxide by L-NAME on the level of free amino acids and biogenic amines in the brain cortex of rats with subtotal cerebral ischemia

2019 ◽  
Vol 16 (3) ◽  
pp. 291-297
Author(s):  
Y. E. Razvodovsky ◽  
V. Y. Smirnov ◽  
Ye. M. Doroshenko ◽  
N. Ye. Maksimovich ◽  
I. N. Semenenya
Keyword(s):  
Nitric Oxide ◽  
Amino Acids ◽  
Cerebral Ischemia ◽  
Free Amino Acids ◽  
Free Amino ◽  
Brain Cortex ◽  
Reversed Phase ◽  
Reversed Phase Hplc ◽  
Mechanisms Of Development ◽  
The Brain

Mechanisms of development of ischemic stroke are complex and have not been fully established. The aim of this study was to estimate the changes in the pool of free amino acids and biogenic animes in the brain cortex of rats with subtotal cerebral ischemia (SCI) and treated with L-NAME. Experiment was made on 18 rats: 12 animals were undergoing bilateral filament occlusion of arteries carotid, 6 of them were treated with L-NAME. The analyses of free amino acids levels in the blood plasma extracts were carried out by reversed phase HPLC.Concentrations of several amino acids were elevated during SCI including aspartate, b-alanine, valine and leucine. In contrast, the levels of glutamate, asparagine, treonine, gamma-aminobutiric acid, tyrosine and 5-hydroxiindolylacetate were decreased. The administration of L-NAME partially prevented the imbalance of the amino acids pool due to SCI by normalizing the levels of aspartate, glutamate, asparagine, methionine, gamma-aminobutiric acid, b-alanine, 5-hydroxiindolylacetate. However, the administration of L-NAME has induced an additional imbalance in the amino acids pool in the brain cortex (decrease in the levels of glutamine, histidine, taurine, tryptophan, phenylalanine, tyrosine (in comparison to SCI) and decrease in the levels of treonine and arginine. The imbalance of the amino acids pool induced by the administration of L-NAME during SCI is more severe than the imbalance caused by SCI.

scholarly journals Possible Role of Fat Tissue in the Pharmacokinetics of Dodeca-2E,4E,8Z,10E/Z-tetraenoic Acid Isobutylamides after Oral Administration of Echinacea angustifolia Extract in Rats

2014 ◽  
Vol 9 (6) ◽  
pp. 1934578X1400900
Author(s):  
Nikoletta Jedlinszki ◽  
Dóra Rédei ◽  
József Haller ◽  
Tamás F. Freund ◽  
Judit Hohmann ◽  
...  
Keyword(s):  
Oral Administration ◽  
Plasma Concentrations ◽  
Pharmacological Action ◽  
Reversed Phase ◽  
Root Extract ◽  
Fat Tissue ◽  
Tetraenoic Acid ◽  
Echinacea Angustifolia ◽  
The Brain

Alkamides are one of the most important constituents of lipophilic extracts of Echinacea angustifolia roots. These compounds play an important role in the versatile pharmacological actions of this plant. The present study aimed to compare the concentrations of isomeric dodeca-2 E,4 E,8 Z,10 E/ Z-tetraenoic acid isobutylamides (DTAI) in brain and periepididymal fat tissues and blood plasma of rats. Thirty, 60, 240 and 720 min after the oral administration of E. angustifolia root extract, tissue and plasma concentrations were determined by reversed-phase HPLC with ESI-MS/MS detection. The calculated terminal t½ of the mixture of DTAI was 8.28 h, which indicates a relatively slow elimination. In the 0.5–4 h period the brain/plasma and fat/plasma concentration ratios were continuously above 3 and 18, respectively, followed by equilibrium at 12 h. Our results indicate substantial accumulation of alkamides in lipid-rich tissues, which presumably contributes to a maintained pharmacological action.

scholarly journals Tissue distribution of S-adenosylmethionine and S-adenosylhomocysteine in the rat. Effect of age, sex and methionine administration on the metabolism of S-adenosylmethionine, S-adenosylhomocysteine and polyamines

1977 ◽  
Vol 166 (3) ◽  
pp. 521-529 ◽  
Author(s):  
Terho O. Eloranta
Keyword(s):  
Tissue Distribution ◽  
Specific Activity ◽  
Tissue Concentration ◽  
Intraperitoneal Administration ◽  
Methionine Adenosyltransferase ◽  
Limiting Factor ◽  
Adenosylhomocysteine Hydrolase ◽  
Rate Limiting ◽  
The Brain ◽  
Effect Of Age

The tissue distribution of S-adenosylmethionine, S-adenosylhomocysteine, methionine adenosyltransferase and S-adenosylhomocysteine hydrolase was explored in the rat. Also the effects of methionine administration on the accumulation of S-adenosylmethionine, S-adenosylhomocysteine and polyamines were studied in rat liver, brain and kidney. The tissue distribution of S-adenosylmethionine, S-adenosylhomocysteine, methionine adenosyltransferase and S-adenosylhomocysteine hydrolase was similar in both sexes, and was only slightly changed with age. The specific activity of S-adenosylhomocysteine hydrolase greatly exceeded that of methionine adenosyltransferase, and the concentration of S-adenosylmethionine was higher than that of S-adenosylhomocysteine in all tissues examined. However, the hepatic S-adenosylmethionine/S-adenosylhomocysteine ratio was dependent on food supply and on the age of the animal. No correlation was noticed between the activity of methionine adenosyltransferase and the concentrations of the adenosyl compounds in different tissues. Intraperitoneal administration of methionine resulted in a profound but transient increase in the hepatic concentrations of S-adenosylmethionine and S-adenosylhomocysteine. The concentration of S-adenosylmethionine was elevated also in the brain during the first 2h after methionine injection. The rise of S-adenosylmethionine concentration after methionine treatment could be diminished by simultaneous glycine administration. The results support the view that the rate-limiting factor of S-adenosylmethionine synthesis is the tissue concentration of methionine. They further suggest that glycine N-methyltransferase may have a regulatory role in the utilization of S-adenosylmethionine in the liver.

scholarly journals Repeated oral administration of low doses of silver in mice: tissue distribution and effects on central nervous system

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Camilla Recordati ◽  
Marcella De Maglie ◽  
Claudia Cella ◽  
Simona Argentiere ◽  
Saverio Paltrinieri ◽  
...  
Keyword(s):  
Oral Administration ◽  
Tissue Distribution ◽  
Clinical Chemistry ◽  
Kidney Tissue ◽  
Clinical Signs ◽  
Oral Exposure ◽  
Dependent Manner ◽  
Low Doses ◽  
Dose Dependent ◽  
The Brain

Abstract Background Widespread use of silver in its different forms raises concerns about potential adverse effects after ingestion, the main exposure route for humans. The aim of this study was to investigate in CD-1 (ICR) male mice the tissue distribution and in vivo effects of 4-week oral exposure to 0.25 and 1 mg Ag/kg bw 10 nm citrate coated silver nanoparticles (AgNPs) and 1 mg Ag/kg bw silver acetate (AgAc) at the end of treatment (EoT) and after 4 weeks of recovery. Results There were no treatment-related clinical signs and mortality, and no significant effects on body and organ weights at the EoT and after recovery. Treatment-related changes in hematology and clinical chemistry were found after recovery, the most relevant being a dose-dependent lymphopenia and increased triglycerides in AgNP-treated mice, and increased levels of urea in all treated groups, associated with decreased albumin only in AgAc-treated mice. At the EoT the highest silver concentration determined by Triple Quadrupole ICP-MS analysis was found in the brain, followed by testis, liver, and spleen; much lower concentrations were present in the small intestine and kidney. Tissue silver concentrations were slightly higher after exposure to AgAc than AgNPs and dose dependent for AgNPs. After recovery silver was still present in the brain and testis, highlighting slow elimination. No histopathological changes and absence of silver staining by autometallography were observed in the organs of treated mice. At the EoT GFAP (astrocytes) immunoreactivity was significantly increased in the hippocampus of AgNP-treated mice in a dose-dependent manner and Iba1 (microglial cells) immunoreactivity was significantly increased in the cortex of 1 mg/kg bw AgNP-treated mice. After recovery, a significant reduction of Iba1 was observed in the cortex of all treated groups. TEM analysis of the hippocampus revealed splitting of basement membrane of the capillaries and swelling of astrocytic perivascular end-feet in 1 mg/kg bw AgNP- and AgAc-treated mice at the EoT. Conclusions Our study revealed accumulation and slow clearance of silver in the brain after oral administration of 10 nm AgNPs and AgAc at low doses in mice, associated with effects on glial cells and ultrastructural alterations of the Blood-Brain Barrier.

Pharmacokinetics and Tissue Distribution Study of Ferruginol in Wistar Rat by High-performance Liquid Chromatography

2018 ◽  
Vol 15 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Guiyun Cao ◽  
Suqiao Han ◽  
Keke Li ◽  
Li Shen ◽  
Xiaohong Wang ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Mobile Phase ◽  
High Performance ◽  
Wistar Rat ◽  
Freezing And Thawing ◽  
Promising Candidate ◽  
Distribution Study ◽  
Substance Loss ◽  
Tissue Distribution Study ◽  
The Brain

Background: Ferruginol (FRGN) exhibits a broad range of pharmacological properties which make it a promising candidate for chemoprevention. However, little is known about its absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Methods: A rapid, sensitive and specific HPLC-DAD method was established to quantify FRGN in the plasma and tissues of Wistar rats. After extraction of FRGN with ethyl acetate (EtOAc), chromatographic separation was performed on a YMC ODS C18 column (250 × 4.6 mm I.D., 5 µm) with a mobile phase consisting of methanol-water (92:8, v/v) at a flow rate of 0.9 mL/min. Detection was conducted with a wavelength of 273 nm at 25 °C. Results: The calibration curves for FRGN were linear in the concentration range of 0.5-20 µg/mL for plasma, 0.5-10 µg/mL for heart, liver, spleen, lung, kidney, stomach, intestine, brain and muscle. After three cycles of freezing and thawing, the concentration variations were within ± 7% of nominal concentrations, indicating no significant substance loss during repeated thawing and freezing. The assay was applied to pharmacokinetic and tissue distribution study in rats. Results suggested that lung, heart, liver, spleen and kidney were the major distribution tissues of FRGN in rats, and FRGN could permeate the blood-brain barrier to distribute in the brain of rats. Conclusion: The information provided by this research is very useful for gaining knowledge of the pharmacokinetic process and tissue distribution of FRGN.

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.

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