Circadian Rhythms of Urea Formation and Argininosuccinate Synthetase Activity in Rat Liver

Kobayashi, Hideo; Mizutani-Funahashi, Masumi; Shiosaka, Sadao; Nakagawa, Hachiro

doi:10.1093/jn/108.7.1071

Cited by 19 publications

(3 citation statements)

References 20 publications

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“…The urea concentration and the total urea content of the urine were higher during the night than during the day-time. Consistent with these findings, the urea concentrations in the liver and serum had circadian rhythms with the highest values at 02:00 h and the lowest values at 14:00 h. Argininosuccinate synthetase is considered as the rate limiting enzyme to play a critical role in regulation of urea formation, and thus it seems likely that the circadian rhythm of change in urea concentration might be caused by periodical change in the synthetase activity (Kato et al 1978).…”

Section: Biological Rhythm Research 585supporting

confidence: 60%

Chronotherapeutic influence of fisetin on ammonium chloride-induced hyperammonemic rats

Jayakumar

Subramanian

2013

Biological Rhythm Research

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Ammonia is a key neurotoxin involved in the neurological complications of the liver. Elevated ammonia leads to hyperammonemic condition which affects several important central nervous system functions. Fisetin is one of the naturally occurring flavonoids found in fruits and vegetables; it exhibits a wide variety of therapeutic benefits such as anticancer, antidiabetic, antioxidant, antiangiogenic, and neuroprotective effects. In this present study, chronotherapeutic efficacy of fisetin on ammonium chloride (AC)-induced hyperammonemic rats was aimed to establish the maximum drug effect by determining the best fitting biological time for drug dosing that helps to increase the therapeutic index of fisetin. The antihyperammonemic effect of fisetin was determined by administering (50 mg/kg b.w. oral) to rats at 06:00, 12:00, 18:00 and 24:00 h against AC (100 mg/kg b.w. i.p.) induced hyperammonemic Wistar rats (180-200 g). Amelioration of pathophysiological conditions of AC-induced hyperammonemia rats by fisetin at different time points (06:00, 12:00, 18:00 and 24:00 h) were measured by assessing the circulatory levels of ammonia, urea, uric acid, creatinine, bilirubin, and liver marker enzymes. Fisetin administration at 24:00 h showed more significant effects on those parameters than the other time points (p50.05) and this might be due to pharmacokinetic property of the drug (fisetin) on temporal variations.

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Section: Biological Rhythm Research 585supporting

confidence: 60%

Chronotherapeutic influence of fisetin on ammonium chloride-induced hyperammonemic rats

Jayakumar

Subramanian

2013

Biological Rhythm Research

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“…Arginine (Arg), which plays an important role in the urea cycle, also exhibits suggestive circadian rhythmicity (FDR ϭ 0.215; PT0.6) in our CE-MS data. It is also noteworthy that the final product-Urea-is reported to vary over 24 h in the blood of certain species such as rabbits (41) and rats (42). Interestingly, Reddy et al (43) showed that 3 key enzymes involved in the urea cycle, carbamoyl-phosphate synthetase 1 (CPS1), argininosuccinate synthetase 1 (ASS1), and arginase 1 (ARG1), show circadian rhythms in the liver, the center of the urea cycle and urea formation (43).…”

Section: Discussionmentioning

confidence: 99%

Measurement of internal body time by blood metabolomics

Minami

Kasukawa²,

Kakazu

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

243

177

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Detection of internal body time (BT) via a few-time-point assay has been a longstanding challenge in medicine, because BT information can be exploited to maximize potency and minimize toxicity during drug administration and thus will enable highly optimized medication. To address this challenge, we previously developed the concept, ''molecular-timetable method,'' which was originally inspired by Linné 's flower clock. In Linné 's flower clock, one can estimate the time of the day by watching the opening and closing pattern of various flowers. Similarly, in the molecular-timetable method, one can measure the BT of the day by profiling the up and down patterns of substances in the molecular timetable. To make this method clinically feasible, we now performed blood metabolome analysis and here report the successful quantification of hundreds of clock-controlled metabolites in mouse plasma. Based on circadian blood metabolomics, we can detect individual BT under various conditions, demonstrating its robustness against genetic background, sex, age, and feeding differences. The power of this method is also demonstrated by the sensitive and accurate detection of circadian rhythm disorder in jet-lagged mice. These results suggest the potential for metabolomics-based detection of BT (''metabolite-timetable method''), which will lead to the realization of chronotherapy and personalized medicine.chronotherapy ͉ circadian ͉ metabolome ͉ jet-lag ͉ LC-MS

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“…Feeding frequency also showed its effects on diurnal changes of some metabolite concentrations only in subjects fed twice daily compared to subjects fed by automatic distribution of concentrate (Eicher et al 1999). In rats, liver and serum urea concentrations showed circadian fluctuations that are closely related to food intake, with nocturnal acrophases (Kato et al 1978).…”

Section: Discussionmentioning

confidence: 99%

Influence of different schedules of feeding on daily rhythms of blood urea and ammonia concentration in cows

Piccione¹,

Grasso²,

Fazio³

et al. 2007

Biological Rhythm Research

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Many physiological processes of domestic animals exhibit daily rhythmicity. The goal of the present study was to investigate, in cows, the influence of different schedules of feeding on daily rhythms of blood urea and ammonia concentrations. Fifteen Italian Brown cows, from the same farm, clinically healthy and placed at the same environmental temperature and photoperiod, were used for this study. Thirty days before the experiment, all the subjects were divided into three homogeneous groups of five cows: A group was fed at 08.00, B group was fed at 16.00, both having access to food for two hours (A group 08.00 -10.00; B group 16.00 -18.00) and C group was fed ad libitum. Blood samples were collected at four hour intervals for 72 consecutive hours starting at 08.00 of the first day and finishing at 04.00 of the third day via intravenous cannula inserted into the jugular vein. On each serum, blood urea and ammonia concentrations were assayed. Data analysis was conducted by one-way repeated measures analysis of variance (ANOVA) and by the single cosinor method. ANOVA showed a significant effect of time on all parameters studied, in either day, with P 5 0.0002 for ammonia in A group and P 5 0.0001 for ammonia and P 5 0.0005 for urea in B group. Cosinor analysis identified the periodic parameters and their acrophases (expressed in hours) during the three days of monitoring: urea showed nocturnal acrophases in B group, ammonia showed diurnal acrophases both in A and B groups. Our results suggest the influence of external stimuli, such as feeding time, on the rhythmic pattern of the metabolites involved in liver function and the hypothetic interaction between circadian clocks placed in the liver and the mean circadian system.

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Circadian Rhythms of Urea Formation and Argininosuccinate Synthetase Activity in Rat Liver

Cited by 19 publications

References 20 publications

Chronotherapeutic influence of fisetin on ammonium chloride-induced hyperammonemic rats

Chronotherapeutic influence of fisetin on ammonium chloride-induced hyperammonemic rats

Measurement of internal body time by blood metabolomics

Influence of different schedules of feeding on daily rhythms of blood urea and ammonia concentration in cows

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