Effect of Phenobarbital Treatment on the Activities of Nadph-Dependent Enzymes of Liver Microsomes in Fasted or Sucrose Fed Rats

Kato, Ryuichi

doi:10.1254/jjp.17.181

Cited by 22 publications

(4 citation statements)

References 18 publications

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“…As described previously by Kato et al (32,33), fasting of rats for 24 hr markedly increased hepatic drug-metabolizing activity (7-alkoxycoumarin O-dealkylase) as compared to that in un treated rats (Tables 1-3). Even after fasting, the heterogeneous distribution of the cyto chrome P-450 monooxygenase system was still observed, and higher activity was detected in the median and the right lobes.…”

Section: Resultssupporting

confidence: 73%

Heterogeneous distribution of the cytochrome P-450 monooxygenase system in rat liver lobes.

1982

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Abstract-Enzyme distribution in rat liver lobes was investigated using liver homogenate as the enzyme source. When the content or the activity was expressed on the basis of unit (gram) wet weight of liver tissue, the protein concentration was almost the same throughout the liver, but several enzymes were distributed heterogeneously within the liver. Cytochrome P-450 monooxygenase activity was higher in the median and right lobes of livers, while the left lobe contained a higher concentration of mitochondrial enzymes. Phenobarbital induced cytochrome P-450 monooxygenase, and the activity was still higher in the median and right lobes even after the pretreatment of rats with phenobarbital. On the other hand, administration of 8-naphthoflavone resulted in a uniform increase of cytochrome P-450 (P-448) content throughout the liver to almost the same concentration. Increase of cytochrome P-448-dependent O-dealkylation activity of 7 alkoxycoumarin by the administration of 8-naphthoflavone was much greater in the left lobe compared to that in the median and the right lobes. Heterogeneous distribution of the enzymes in various liver lobes was also determined employing liver samples obtained from various physiological states of rats (fasting, glucose refeeding after fasting and hyperthyroidism), although the cytochrome P-450 content and drug-metabolizing activity were altered markedly depending upon the physiological states of the rats.

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Section: Resultssupporting

confidence: 73%

Heterogeneous distribution of the cytochrome P-450 monooxygenase system in rat liver lobes.

1982

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“…The trend of results on aminopyrine and the significant low clearance of antipyrine on 3000 kcal-5% PE (diet III) clearly suggest that carbohydrate and or fat calories per se are inadequate and unlikely to stimulate drug clearance from plasma (Kato, 1967).…”

Section: Energy Deficit Is High (> 40%) Drug Metabolism Ismentioning

confidence: 99%

“…There is a consistent impairment of antipyrine hydroxylation in all subjects on 3000 kcal with 5% protein energy, whereas aminopyrine metabolism as judged by 4AA excretion and aminopyrine half-life has a constant trend towards impairment. The trend of results on aminopyrine and the significant low clearance of antipyrine on 3000 kcal-5% PE (diet III) clearly suggest that carbohydrate and or fat calories per se are inadequate and unlikely to stimulate drug clearance from plasma (Kato, 1967).…”

Section: Effect Ofdietary Energymentioning

confidence: 99%

Dietary influences on the kinetics of antipyrine and aminopyrine in human subjects.

Krishnaswamy¹,

Kalamegham²,

Naidu³

1984

Brit J Clinical Pharma

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1 The possible dietary influences on in vivo antipyrine and aminopyrine kinetics with reference to energy (1500, 1800, 3000 kcal) and protein (5, 10, 15, 20% protein energy-PE) intake were studied in a carefully controlled metabolic experiment in young healthy adult male volunteers aged between 25-34 years. 2 Antipyrine and aminopyrine were used to evaluate drug metabolism. 3 On 1500 kcal intake with 10% PE, the metabolism of both aminopyrine and antipyrine were significantly reduced whereas on 1800 kcal with 10% PE intake, only aminopyrine metabolism decreased significantly as compared to 3000 kcal with 10% PE. 4 Antipyrine clearance on 1800 kcal with 10% PE however had not decreased to the same extent as on 1500 kcal with 10% PE. The results indicate that on low calorie intake with 10% PE, the drug metabolism is decreased. 5 When the protein intake on 1500 kcal was doubled (20% PE) there was a significant stimulation of both aminopyrine and antipyrine metabolism. 6 Aminopyrine and antipyrine clearances on 3000 kcal with 5% PE were significantly reduced as compared to 3000 kcal with 10% and 15% PE indicating that unlike proteins, carbohydrate and/or fat calories per se do not significantly stimulate drug metabolism. 7 When the protein energy in the diet was increased from 5% to 10% or 15% at 3000 kcal, there was a stimulation of both antipyrine and aminopyrine metabolism. 8 Significant differences between 10% and 15% of protein energy were not observed when the energy was adequate (3000 kcal). 9 Therefore it is necessary to consider both proteins and energy as important variables affecting drug clearances from plasma in malnourished conditions.

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“…Depending upon the species, the sex, and the metabolic pathway examined, starvation was found either to enhance, impair, or leave unchanged the activity of the microsomal enzymes (Dixon et al 1960;Roth and Bukovsky 1961 ;Kato andGillette 1964, 1965;Serve11 et al 1965;Kato 1967aKato , 1967bKato and Takanaka 1967;Kato et al 1969;Gram et (el. 1970;Gigon and Bickel 1971;Bock et al 1973).…”

Section: Introductionmentioning

confidence: 99%

Influence of Starvation on Absorption, Distribution, and Action of Barbital in Mice and Rats

Brodeur¹,

Lalonde²,

Leroux³

1974

Can. J. Physiol. Pharmacol.

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BROI,E~R, J., LALONDE, S.. and LEROUX, J. 1974. Influence of starvation on absorption, distribution, and action of barbital in mice and rats. Can. J. Physiol. Pharmacol. 52, 1192-1200 The influence of food deprivation on the disposition of barbital during the early phase following ~dministration of the drug was studied in mice and rats. Starvation consisted of withholding solid food, but not water, for 24-72 h in mice, and 72 h in rats. The results show that starvation leads to higher blood concentrations of barbital given intraperitoneally (i.p.1 and subcutaneously to mice and rats, apd intramuscularly to rats. This effect was observed 2.5-10 min following the injection of the barbiturate. In mice, starvation significantly reduced the interval between injection of the drug and loss of the righting reflex. but it extended the tluration of the sleeping period. When barbital was given intravenously, starvation no longer resulted in higher blood comncentrations of the drug, although starved mice went to sleep more rapidly than fed controls. At the moment of loss of the righting reflex. starved mice had significantly lower concentrations of barbital in the brain than fed controls. The total blood and plasma volumes of starved animals were tnoderately increased when expressed as a percentage of the body weight. These results suggest that starvation tnight influence the early phase of barbital absorption following its parenteral administration. There is also an indication that starvation could induce a state of hypersensitivity of the central nervous system to barbital. R R~D E U R , J., LALONDE, S. et I[,EROUX, J . 1974. Influence of starvation on absorption, distribution, and action of barbital in mice and rats. Can. J. Physiol. Pharmacol. 52, 1192-1200. Nous avons CtridiC l'influence d'une ptriode de jeiine aigri sur le sort metabolique du barbital au cours des quelques minutes qui suivent son administration. chez In souris et le rat. Nous avons enlev6 toute nourriture solidc, rr~ais norm l'eau de brenvage, pendant tine pkriode de 24 L 72 h chez la souris, et pendant une pCriode de 72 h c h e~ Ie rat.Ides r6sultats obtenus nlontrent que le jeijne entraine une augmentation de la concentration sanguine du barbital administrt par voie intrap6ritonCale et sous-cutanke, chez la souris et le rat, ainsi que de celle du barbital adtninistrC par voie intrn-musculaire, chez 1e rat. Get effet s'observe au cours des qtlelques 2.5 & 10 nlin qui suivent I'injection du barbital. Chez la souris, le jeiine rCduit le temps d'induction au somnmeil, suite & l'administration du barbital. rnais prolonge la durCe totale du somrneil. I,orsque le barbital est ad~ninistri par voie intraveineuse, le jeiine ne modifie pas la concentration sanguine du barbital, nlais il riduit neanmoins le temps d'induction au sommeil. I,a concentration cCrCbrale du barbituriqrie est abaissCe chez les souris i jeun par rapport aux souris contrbles, au moment ou les animaux s'endorment. Enfin, le jei~ne entraine une augmentation relative des volun~es sanguin et...

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Effect of Phenobarbital Treatment on the Activities of Nadph-Dependent Enzymes of Liver Microsomes in Fasted or Sucrose Fed Rats

Cited by 22 publications

References 18 publications

Heterogeneous distribution of the cytochrome P-450 monooxygenase system in rat liver lobes.

Heterogeneous distribution of the cytochrome P-450 monooxygenase system in rat liver lobes.

Dietary influences on the kinetics of antipyrine and aminopyrine in human subjects.

Influence of Starvation on Absorption, Distribution, and Action of Barbital in Mice and Rats

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