Related Experiment Video
Updated: Jul 9, 2026
A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s
Published on: September 25, 2017
Nicotinamide metabolites accumulate in the tissues of uremic rats
Przemysław Rutkowski1, Ewa M Slominska, Wojciech Wołyniec
1Department of Nephrology, Transplantation, and Internal Diseases, Medical University Gdansk, Gdansk, Poland. prut@amg.gda.pl
Objective:
N-methyl-2-pyridone-5-carboxamide (Met2PY) and N-methyl-4-pyridone-3-carboxamide (Met4PY) are nicotinamide (NA) metabolites described by our group and considered to be uremic toxins. Plasma concentration of Met2PY and Met4PY in end-stage renal disease (ESRD) is several-fold higher in comparison with healthy controls. However, there are no data about the concentrations of these compounds in different tissues. The aim of this study was to establish whether the observed high concentrations of these compounds were also present in different tissues of uremic animals.
Methods:
This study was conducted in 10 5/6 nephrectomized male Wistar rats and 10 sham-operated animals. Concentrations of nicotinamide and its end products were measured using high-performance liquid chromatography and mass spectrometry.
Results:
We observed significant elevations of Met2PY and Met4PY in tissues of uremic rats. The greatest differences between healthy and uremic rats were observed in the liver, lungs, and skeletal muscles. Accumulation in the kidney and heart was not so pronounced, but in the case of Met4PY was statistically significant.
Conclusions:
We found that Met2PY and Met4PY accumulate not only in the blood but also in tissues of uremic rats.
Related Concept Videos
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
01:24Chronic Kidney Disease II: Clinical Manifestations
01:23Drugs Acting on Autonomic Ganglia: Stimulants
Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or...