• 한국식품영양과학회지
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• 제23권1호
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• pp.13-22
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• 1994

This study was designed to investigate the effects of dietary protein and caffeine consumption levels on Ca, P, Na and K metabolism. One hundred twenty rats were divided into twelve groups according to age, protein level and caffeine consumption such as group(120-130g young rat, 250-300g adult rat) , dietary protein group (20% normal protein , 85 low protein) , caffeine consumption group(0, 3.5mg, 7.0mg). Low protein diet containing high caffeine levels caffeine levels increased calcium, phosphorus, sodium and potassium contents of urine and fecal in rats. Young rat has higher level of calcium, phosphorus , sodium and potassium than adult rat. In the serum, calcium contents were not affected by age, dietary protein levels and caffeine consumption . However, phosphorus, sodium and potassium contents of serum in adult rat were higher than young rat. In the liver, potassium decreased with decreasing dietary protein levels. In the kidney, calcium , phosphorus and potassium contents were not different by age group, dietary protein levels and caffeine consumption , but sodium content was significantly reduced in the adult rat.

• Journal of Nutrition and Health
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• 제29권9호
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• pp.950-957
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• 1996

This study was designed to investigate the effects of caffeine intake on Ca and P metabolism in ovariectomized rats. For this purpose, the ovariectomized female rats weighing 230.8$\pm$3.5g were divided into four groups, eight rats each ; control, low caffeine(LC), medium caffeine(MC)and high caffeine(HC) groups. They were supplied for six weeks with the caffeine of 0mg, 66.8mg, 167mg and 334mg per kilogram of diet, respectively, and the results are summarized as follows. 1) There were no significant differences in feed intake, feed efficiency ratio and body weight change among all of experimental groups. But liver weight(both total weight and weight/body weight) was significantly decreased by caffeine in MC group. 2) The weight of tibia was decreased by caffeine intake in MC and HC groups. But the length, Ca and P content of tibia and femur was not changed in all of caffeine groups. 3) Ca, PTH and calcitonin levels in serum were not affected by caffeine. While, serum P level in HC group was significantly increased as compared with the control. 4) The fecal excretion of Ca and P tended to be higher in the caffeine groups, and as the result, the absorption rate, retention and retention rate of Ca and P tended to be decreased. It was noteworthy that P retention was significantly lowered in HC group as compared with LC group. The results showed that, when caffeine was taken by ovarietomized rats, the weight of tibia was decreased and the retention rate of Ca and P tended to be lowered. Therefore, too much intake of caffeine for women whose bone mineral density of tibia is decreased after postmenopause seems to accelerate the decrease of bone mineral density due to the negative effect on metabolism of Ca and P.

• Journal of Nutrition and Health
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• 제29권7호
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• pp.713-720
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• 1996

To study the effect of caffeine intake levels on iron metabolism, the iron utilization, iron contents of serum, liver, spleen, kidney, hemoglobin and hematocrit were compared in rats of different sex fed various levels of caffeine (3.5 and 7.0mg/100g body weight) for three weeks. There were no significant caffeine induced differences in feed intake, body weight gain but feed intake of male rats were significantly lower than that of female rats. Hemoglobin, hematocrit and iron contents of the serum were not significantly different between caffeine free and caffeine groups or male and female rats. Iron contents of kidney were decreased by elevation of injected caffeine levels rather than those of liver and spleen. caffeine male groups showed more increased uine volume, urinary and fecal excretions of iron than caffeine free or caffeine female groups. Apparent digestibility and retention of iron were significantly decreased by increment of injected caffeine levels. Male rate rats were more susceptible to injected caffeine on iron excretion than female rats. Current findings suggest that excessive caffeine consumption can affect iron excretion via urine and feces thereby decrease the utilization of iron, and have more significant effect on male than female rats.

• 한국식품영양과학회지
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• 제22권6호
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• pp.658-663
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• 1993

식이성 비타민 E의 급여수준이 카페인을 투여한 흰쥐의 지질대사에 미치는 영향을 검토하고자, 카페인을 무첨가 또는 0.3% 첨가시킨 식이에 비타민 E를 각각 세가지 급여수준(37.5, 750 및 1,500mg/kg diet)으로 사육기간을 5주와 10주로 하여 사육한 결고는 다음과 같다. 체중증가량, 식이섭취량 및 식이효율은 카페인 급여군에서 비타민 E 단독부여군에 비해 유의하게 감소하였고, 체중 100g당 간과 신장의 중량은 카페인 첨가군에서 유의한 증가를 보였다. 혈청과 간의 total lipid 함량은 카페인 첨가군에서 비타민 E 급여수준을 증가시킬수록 감소하였다. 혈청중 cholesterol함량은 카페인을 첨가하였을 때는 증가하였으나, 간장중 cholesterol의 함량은 비타민 E의 급여수준을 증가시킴에 따라 감소하는 경향이었다. Triglyceride함량은 혈청과 간 모두 카페인 첨가군에서 유의하게 감소하였으며, 그 감소의 정도는 비타민 E 급여수준이 증가할수록 크게 나타났다. 또 혈청 alanine aminotransferase와 aspartate aminotransferase의 활성은 모든 실험군에서 유의한 차이가 없었다.

• Biomolecules & Therapeutics
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• 제24권4호
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• pp.446-452
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• 2016

Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism.

• Journal of Nutrition and Health
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• 제25권7호
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• pp.597-607
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• 1992

The present study examined effects of caffeine on coronary circulation myocardial oxygen me-tabolism and calcium release in isolated perfused guinea pig hearts. Intracoronary caffeine({{{{ {10 }^{-5 } }}}}∼{{{{ { 10}^{-3 } }}}}M) was employed for 10 minutes to measure coronary perfusate flow(CF) and coronary vascular sresistance(CVR) at a constant coronary perfusion pressure of 80 cmH2O Perfusate myocardial oxygen consumption(MVO2) and percent oxygen extraction(%EC2) were calcula-ted. In addition calcium contents in both perfusate samples were measured to calculate calcium release in coronary venous effluent. Caffeine significantly decreased CF and increased CVR during 10 minutes of caffeine perfusion regardless of dose of caffeine perfused exhibiting time-response. While % EO2 was significantly enhanced with caffeine MVO2 was markedly reduced. The coronary venous perfusate pH dcreased during the perfusion with caffeine. These changes were consistent with caffeine-induced metabolic acidosis. Calcium release appeared to be dose-dependent and high dose of caffeine greatly increased venous calcium release even 2 minutes after perfusion with carffeine. These finding in dicate that caffeine produced coronary vasoconst-riction with increased calcium release in isolated perfused guinea pig hearts. Additionaly this vasoconstrictor response mignt be due tin part to the direct actions of caffeine.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.122-122
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• 1998

Propentofylline (PPF), a xanthine derivative, has been reported to be effective for the treatment of both vascular dementia and Alzheimer's disease. The elimination half-life of PPF was ranged from 15 to 45 min in rabbit and human, and PPF was rapidly disappeared from the blood. The objective of this experiment is to investigate whether xanthine analogues have effects on the profile of plasma concentration and metabolism of PPF. Caffeine (50 mg/kg, ip) was treated to Sprague-Dawley rats for consecutive 7 days and PPF was intravenously administered to rats 2 hr after the last dose of caffeine. In the other group, PPF was intravenously administered to rats 1 hr after a single dose of pentoxifylline (50 mg/kg, iv). Control group was treated with saline vehicle for the same period as in treatment groups. Blood was withdrawn at specific time intervals. PPF and one of its metabolite (POH) in plasma were determined by gas chromatography/nitrogen phosphorus detector. Plasma concentrations and pharmacokinetic parameters were compared between groups. The area under the curve (AUC) of PPF in rats treated sub chronically with caffeine was significantly decreased compared to control rats. Caffeine treatment results in a significant increase of total body clearance. The AUC of POH was significantly decreased in the caffeine-treated group. A single dose of pentoxifylline has no effect on the phramacokinetics of PPF. Reduction of the AUCs of PPF and POH both suggests that caffeine may increase the excretion of PPF with no affecting the metabolism of PPF to POH.

• Toxicological Research
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• 제13권1_2호
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• pp.117-125
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• 1997

In order to assess the possibility whether CYP2D is involved in caffeine metabolism, we have purified and characterized the rat liver microsomal cytochrome P4502D1 (CYP2D1), equivalent to CYP2D6 in human liver, and have utilized the reconstituted CYP2D1 in the metabolism of 4 primary caffeine (1, 3, 7-trimethylxanthine) metabolites such as paraxanthine (1, 7-dimethylxanthine), 1, 3, 7-trimethylurate, theophylline (1, 3-dimethylxanthine) and theobromine (3, 7-dimethylxanthine). Rat liver CYP 2D1 has been purified to a specific content of 8.98 nmole/mg protein (13.4fold purification, 1.5% yield) using $\omega$-aminooctylagarose, hydroxlapatite, and DE52 columns in a sequential manner. As judged from sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), the purified CYP2D1 was apparently homogeneous. Molecular weight of the purified CYP2D1 was found to be 51, 000 Da. Catalytic activity of the purified and then reconstituted CYP2D1 was confirmed by using bufuralol, a known subsFate of CYP2D1. The reconstituted CYP2D1 was found to produce to 1-hydroxylbufuralol at a rate of 1.43$\pm$0.13 nmol/min/nmol P450. The kinetic analysis of bufuralol hydroxylation indicated that Km and Vmax values were 7.32$\mu M$ and 1.64 nmol/min/nmol P450, respectively. The reconstituted CYP2D1 could catalyze the 7-demethylation of PX to 1-methylxanthine at a rate of 12.5 pmol/min/pmol, and also the 7- and 3- demethylations of 1, 3, 7-trimethylurate to 1, 3-dimethylurate and 1, 7-dimethylurate at 6.5 and 12.8 pmol/min/pmol CYP2D1, respectively. The reconstituted CYP2D1 could also 3-demethylate theophylline to 1-methylxanthine at 5 pmol/min/pmol and hydroxylate the theophylline to 1, 3-dimethylurate at 21.8 pmol/min/pmol CYP2D1. The reconstituted CYP2D1, however, did not metabolize TB at all (detection limits were 0.03 pmol/min/pmol). This study indicated that CYP2D1 is involved in 3-and 7-demethylations of paraxanthine and theophylline and suggested that CYP2D6 (equivalent to CYP2D1 in rat liver) present in human liver may be involved in the secondary metabolism of the primary metabolites of caffeine.

• 운동영양학회지
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• 제15권4호
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• pp.183-189
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• 2011

Caffeine and capsaicin increase resting energy metabolism. However, most measurements have been conducted in short-term studies. Therefore, we investigated the effects of caffeine and capsaicin on energy expenditure and energy substrate utilization in resting rats for 6 h. The caffeine (Experiment 1) experiment included four male rats aged 5 weeks and measured the effects of oral administration of caffeine (10 or 50 mg/kg) on respiratory gas, energy expenditure, and energy substrate oxidation for 6 h. Experiment 2 included four male rats aged 6 weeks to measure the effects of capsaicin (10 mg/kg) using the same method as in Experiment 1. The results of Experiment 1 indicated that O₂ uptake and carbohydrate oxidation after caffeine administration for 2 h was higher in the 10 mg trial than that in the 50 mg or placebo trials (P < 0.05). However fat oxidation was not significantly different. In contrast, capsaicin (Experiment 2) observed no differences between the placebo and the capsaicin trials. In conclusion, caffeine initially increased the resting energy consumption for 2 h, and this energy expenditure was due to carbohydrate oxidation. Capsaicin did not change oxygen uptake, respiratory exchange ratio, fat oxidation, or carbohydrate oxidation.

• Biomolecules & Therapeutics
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• 제19권2호
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• pp.243-247
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• 2011

Rutaecarpine, an alkaloid originally isolated from the unripe fruit of Evodia rutaecarpa, has been shown to be anti-inflammatory. In the present study, a possible interaction between rutaecarpine and caffeine was investigated in male Sprague Dawley rats. Twenty four hr after the oral pretreatment with rutaecarpine at 80 mg/kg for three consecutive days, rats were treated intravenously with 10 mg/kg of caffeine. Compared with control rats, the pharmacokinetic parameters of caffeine in rutaecarpine-pretreated rats were significantly changed, possibly due to the rapid metabolism. The production of three metabolites of caffeine (i.e., paraxanthine, theobromine and theophylline) was also significantly changed in rats pretreated with rutaecarpine. The present results suggest that oral rutaecarpine would change the intravenous pharmacokinetic characteristics of caffeine.