ABSTRACT
ObjectiveTo evaluate the metabolic stability of lucidin by incubating liver microsomes and liver S9 from 4 species， and to compare the species differences in metabolism of lucidin in vitro. MethodA qualitative and quantitative method of lucidin based on ultra-high performance liquid chromatography-high resolution mass spectrometry （UHPLC-HRMS） was established and verified. Lucidin was incubated with rat， mouse， beagle dog， human liver microsomes and liver S9 to investigate the metabolic stability parameters， metabolites， metabolic pathways. ResultHepatic clearance （CLh） of lucidin was in order of mouse>rat>beagle dog>human in both phase Ⅰ and phase Ⅱ incubation system. Its metabolic stability was good in rat， beagle dog and human， while it showed metabolic instability and moderate metabolic stability in mouse microsomes and liver S9， respectively. A total of 5 metabolites were rapidly identified， including 3 oxidation metabolites of phase Ⅰ and 2 sulfation metabolites of phase Ⅱ. The production rate of metabolites was consistent with the results of metabolic stability. ConclusionThe established UHPLC-HRMS is simple and specific， which can be used for the study on the metabolic stability and metabolites of lucidin. Its metabolic stability and metabolite production rate in vitro are significantly different among species， the metabolic characteristics of rat and beagle dog are similar to human， which provides an important reference for subsequent research in vivo， safety evaluation and animal model selection of lucidin.
ABSTRACT
Caffeine and its metabolic products play an important role in clinical applications. An ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF MS/MS) method was applied to systemically study the caffeine metabolism in liver microsomes of rats and mice, and comprehensively evaluate caffeine metabolites in vitro and metabolism differences between species. The caffeine metabolites and metabolism differences between species in liver microsomes of rats and mice were analyzed by UPLC-Q-TOF-MS/MS high resolution mass spectrometry system and metabolitepolite software. The results showed that in addition to the demethylated and oxidized products in previous analysis, methylated, double oxidized, dehydrated and decarbonylated metabolites were also found in caffeine metabolism in liver microsomes of rats and mice, with significant difference in metabolism in vitro between rats and mice. The demethylated metabolite M2(C7H8N4O2) and decarbonylated metabolite M6(C7H10N4) in metabolism in vitro of mice were not found in rats, and the in vitro metabolite M7(C8H12N4O5) in rats were not found in mice. There was significant species difference in caffeine metabolism in vitro between rats and mice, providing important reference value for the further metabolism study and safety evaluation of caffeine.
ABSTRACT
La mayoría de los organismos, incluyendo los humanos, exhiben ritmos diarios de aproximadamente 24 horas en fisiología, funciones hormonales y conducta. En mamíferos, estos ritmos son controlados por un marcapasos circadiano endógeno ubicado en el núcleo supraquiasmático (NSQ) del hipotálamo que determina la organización temporal de varias conductas y procesos fisiológicos. El control circadiano de ritmos diarios difiere en especies diurnas y nocturnas pero los mecanismos que pueden explicar dichas diferencias se desconocen aún. El objetivo de esta revisión es resumir el estado actual del conocimiento sobre los relojes circadianos y de las diferencias entre especies diurnas y nocturnas.
Most organisms, including humans, show daily rhythms of about 24 hours in physiology, hormonal function, and behavior. In mammals, these rhythmsare controlled by an endogenous circadian pacemaker localized in the suprachiasmatic nucleus (SCN) of the hypothalamus that determines thetemporal organization of several behaviors and physiological processes.Circadian control of daily rhythms differs in diurnal and nocturnal speciesbut many of the mechanisms that may explain these differences remain stillunknown. The aim of this review is to summarize our current knowledge of the circadian clocks and the differences between diurnal and nocturnal species.
Subject(s)
Humans , Activity Cycles/physiologyABSTRACT
This study was conducted to examine the species differences in the urinary excretion of trichloroethanol(TCE-OH) and trichloroacetic acid(TCA) of trichloroethylene(TCE) metabolites and the effect of ethanol on these metabolites in mice and rats. TCE administered to Male Sprague Dawley rats and ICR mice as a single oral dose(100, 200, 500, 1,000 or 2,000 mg/kg body weight) and ethanol(3.0 g/kg body weight) was taken orally 12 hours before TCE administration. The metabolites in urine were measured 0, 12, 24, 36 and 48 hours after TCE administration. The results of metabolite excretion were as follows; Total trichlorocompounds(TTC) in urine increased with TCE dose in mice while increased only below dose of 1,000 mg/kg TCE in rats. The net excretion of TCE metabolites was significantly greater in mice than rats, although the proportion of TCE-OH to TCA was not different between mice and rats. These findings indicate that mice were internally exposed to significantly higher concentration of TCE metabolites than rats and this trend appeared to be more prominent with the increase of TCE dose. Ethanol increased significantly TCE-OH in urine of rats while the increase of TCE-OH induced by ethanol was not significant in mice, and didn't increase TCA of urine in both of rats and mice. This result suggests that the effect of ethanol on TCE metabolism may be due to the increase of TCE-OH.