Drug-Induced Changes in the Liver Endoplasmic Reticulum: Association with Drug-Metabolizing Enzymes

Remmer, H.; Merker, H. J.

doi:10.1126/science.142.3600.1657

Cited by 384 publications

(87 citation statements)

References 8 publications

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“…Thus, it seems that the decrease in ALT and AST activities enhanced the induction of microsomal drug-metabolizing enzymes, and these regulatory controls may act to conserve nutrients and energy for the cells. These results are in consonance with the studies of Orrhenuis et al (1965), Marshall (1978, Remmer and Merker (1993), and Singh et al (1998). The reports of these workers showed that increased protein synthesis due to increased glucuronidation of the endoplasmic reticulum and decreased permeability of the liver cells resulted in induction of the microsomal drugmetabolizing enzymes.…”

Section: Discussionsupporting

confidence: 82%

Effect of caffeine -coconut products interactions on induction of microsomal drug-metabolizing enzymes in wistar albino rats

Abara

Obochi²,

Malu³

et al. 2010

Nig. J. Phys Sci

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Summary: Effect of caffeine-coconut products interactions on induction of drug-metabolizing enzyme in wistar albino rats was studied. Twenty rats were randomly divided into four groups: The control group (1) received via oral route a placebo (4.0ml of distilled water). Groups 2 to 4 were treated for a 14-day period with 50mg/kg body weight of caffeine, 50mg/kg body weight of caffeine and 50mg/kg body weight of coconut water, and 50mg/kg body weight of caffeine and 50mg/kg body weight of coconut milk in 4.0ml of the vehicle via gastric intubation respectively. One day after the final exposure, the animals were anaestheticized by inhalation of an overdose of chloroform. The blood of each rat was collected by cardiac puncture while the liver of each rat was harvested and processed to examine several biochemical parameters, ie, total protein and RNA levels, protein/RNA ratios, and activities of alanine and aspartate amino transferase (ALT and AST, respectively). The results showed that while ingestion of coconut milk and coconut water increased the values of protein and protein/RNA ratios, it decreased alanine and aspartate amino transferase (ALT and AST) activities. These effects, in turn, enhanced the induction of the metabolizing enzymes and a resultant faster clearance and elimination of the caffeine from the body, there by reducing the toxic effect on the liver.

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Section: Discussionsupporting

confidence: 82%

Effect of caffeine -coconut products interactions on induction of microsomal drug-metabolizing enzymes in wistar albino rats

Abara

Obochi²,

Malu³

et al. 2010

Nig. J. Phys Sci

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“…Differential induction of microsomal CYP activities by aryl hydrocarbons and phenobarbital was discovered over 50 years ago [1][2][3][4], and facilitated characterization of the CYP supergene family [5,6]. This discovery also stimulated identification of the responsible ligand-activated transcription factors (LATFs): AhR [7,8], CAR and PXR [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the present commentary emphasizes regulation of human hepatic UGTs by LATFs and their multilevel crosstalk. 4 …”

Section: Introductionmentioning

confidence: 99%

From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans

Bock¹

2011

Biochemical Pharmacology

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. From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans. Biochemical Pharmacology, Elsevier, 2011, 82 (1) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64

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“…The administration of phenobarbital markedly increases the activities of drug-oxidiz ing, drug-reducing enzymes and NADPH-dependent electron transport enzymes and the amounts of cytochrome b5 and P-450 (2,4,5,15,16,32,33,36,37). Since the effect of phenobarbital is likely due to an increased synthesis of the microsomal enzymes (2, 38 42), the effect of phenobarbital on the activities of drug-metabolizing enzymes and NADPH dependent electron transport system was investigated.…”

Section: Fig 1 Activities Of Pentobarbital Oxidase Carisoprodol Oxmentioning

confidence: 99%

Drug Metabolism in Tumor-Bearlng Rats

Kato

Takanaka

Takahashi

et al. 1968

Japanese Journal of Pharmacology

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It has recently been recognized that the metabolism of lipid soluble compounds by liver microsomal enzymes is highly important factors for controlling the action and toxicity of various drugs (1-5). This fact is, especially, important for some drugs which should be converted to the active metabolite in vivo (5-7). Some carcinogenic and carcinostatic compounds, such as dimethylnitrosamine, 2-acethylaminofluorene, 4-nitroquinoline N oxide and cyclophosphoramide, belong to this group (8-11).The activities of drug-metabolizing enzymes of liver microsomes are markedly altered by several factors, such as, the administrations of different kind of lipid soluble compounds and anabolic hormones, starvation, low protein diet, formaline and adrenaline stress, al loxan diabetes, hyperthyroidism, adrenalectomy, viral hepatitis and hepatectomy (1,3,(12)(13)(14)(15)(16)(17)(18)(19)(20).In a preliminary work,* we observed a decrease in the metabolism of pentobarbital, meprobamate and strychnine in Walker 256 carcinosarcoma bearing male rats. How ever, there are clear sex difference in the alternation of activities of drug-metabolizing enzymes by the non-physiological conditions. For example, starvation, formalin and ad renaline stress, alloxan diabetes, hyperthyroidism and adrenalectomy markedly decrease the activities of most of the enzymes in male rats, while they did not significantly alter or rather increased the activities in female rats (13,14).It would be, thus, interesting to investigate whether the decrease in the metabolism of drugs by liver microsomes of the tumor-bearing rats is only limited to male rats. Moreover, whether the activities of other drug-oxidizing enzymes, drug-reducing enzymes and electron transport systems is affected or not by tumor-bearing was investigated.Furthermore, in order to obtain some insights in the mechanism of decrease in the activities of drug-metabolizing enzymes in tumor-bearing rats, the effect of phenobarbital treatment on these enzyme activities in control rats and tumor-bearing rats was compara tively investigated.

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Drug-Induced Changes in the Liver Endoplasmic Reticulum: Association with Drug-Metabolizing Enzymes

Cited by 384 publications

References 8 publications

Effect of caffeine -coconut products interactions on induction of microsomal drug-metabolizing enzymes in wistar albino rats

Effect of caffeine -coconut products interactions on induction of microsomal drug-metabolizing enzymes in wistar albino rats

From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans

Drug Metabolism in Tumor-Bearlng Rats

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