MORPHOLOGICAL AND FUNCTIONAL CHANGES IN P‐GLYCOPROTEIN DURING DEXAMETHASONE‐INDUCED HEPATOMEGALY (English)

in Clinical and Experimental Pharmacology and Physiology ; 34 , 4 ; 296-303
Clinical and Experimental Pharmacology and Physiology
Blackwell Publishing Asia ; 2007

The effect of dexamethasone on hepatic and renal P‐glycoprotein (P‐gp) expression, localization and activity was investigated in rats after 4 days oral administration of two dose regimens (1 or 25 mg/kg per day). Simultaneous increases in liver weight were evaluated by quantitative histological examination.

In the liver, dexamethasone pretreatment produced hepatomegaly as a consequence of extensive periportal fat accumulation, which was quantified by densitometry of oil red O‐stained liver sections. Quantitative immunohistochemical analysis revealed preferential periportal zonation of P‐gp in control animals. Dexamethasone pretreatment resulted in spatially disproportional induction of P‐gp protein expression within the liver acinus characterized by preferential increase in pericentral areas, with consequent uniform panlobular distribution. Western blot analysis confirmed these results, showing increases in P‐gp protein. Quantitative reverse transcription–polymerase chain reaction analysis revealed no statistically significant change in liver mdr1b mRNA expression after either dexamethasone treatment regimen. The expression of mdr1a mRNA was significantly decreased by 85–87%.

In the kidney, dexamethasone reduced mdr1a mRNA expression by 69–89%, whereas mdr1b mRNA expression was increased in a dose‐dependent manner. However, despite tendencies, no significant increases in P‐gp expression were observed at the protein level.

The in vivo function of P‐gp was evaluated by measuring renal and biliary secretion of rhodamine‐123 (Rho123) under a steady state plasma concentration. The biliary, renal and tubular secretory clearance of Rho123 was significantly increased only after high‐dose dexamethasone.

In conclusion, the present study suggests that drug interactions observed during corticosteroid therapy may be mediated, at least in part, through increased biliary, and also renal, excretion of P‐gp substrates. Expression of P‐gp in the liver showed primary periportal zonation with differential changes during induction. Accompanying hepatomegaly may be explained by severe microvesicular steatosis selectively localized to the periportal areas.

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Table of contents – Volume 34, Issue 4

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Tables of content are generated automatically and are based on records of articles contained that are available in the TIB-Portal index. Due to missing records of articles, the volume display may be incomplete, even though the whole journal is available at TIB.

255
DIFFERENCES BETWEEN PATHOLOGICAL AND PHYSIOLOGICAL CARDIAC HYPERTROPHY: NOVEL THERAPEUTIC STRATEGIES TO TREAT HEART FAILURE
McMullen, Julie R / Jennings, Garry L | 2007
263
INVESTIGATION OF THE MICROCIRCULATION AND THE STATE OF OXIDATIVE STRESS IN THE RAT AFTER SCORPION ENVENOMATION
Sahnoun, Z / Chaker‐Krichen, S / Kassis, M / Hakim, A / Hammami, S / Ghozzi, H / Bouayed, N / Bellasfar, Z / Zeghal, KM / Rebai, T | 2007
269
SPATIAL PULMONARY FLOW DISTRIBUTION IN RABBIT ISOLATED LUNGS IS A POOR REPRESENTATION OF THE SITUATION IN VIVO*
Hübler, M / Heller, AR / Bleyl, JU / Rössel, T / Stehr, SN / Koch, T | 2007
274
EFFECT OF HIGH SALT INTAKE ON LOCAL RENIN–ANGIOTENSIN SYSTEM AND VENTRICULAR DYSFUNCTION FOLLOWING MYOCARDIAL INFARCTION IN RATS
De Resende, Micheline M / Mill, José G | 2007
280
INVOLVEMENT OF THE ENDOTHELIN ETB RECEPTOR IN GENDER DIFFERENCES IN DEOXYCORTICOSTERONE ACETATE‐SALT‐INDUCED HYPERTENSION
Kawanishi, Hideaki / Hasegawa, Youichi / Nakano, Daisuke / Ohkita, Mamoru / Takaoka, Masanori / Ohno, Yukihiro / Matsumura, Yasuo | 2007
286
IDENTIFICATION OF LIGANDS BINDING SPECIFICALLY TO INFLAMMATORY INTESTINAL MUCOSA USING PHAGE DISPLAY
Takagi, Tamaki / Arisawa, Tomiyasu / Yamamoto, Kazumasa / Hirata, Ichiro / Nakano, Hiroshi / Sawada, Makoto | 2007
290
PHARMACOKINETICS AND PHARMACODYNAMICS OF A NITRIC OXIDE‐RELEASING DERIVATIVE OF ENALAPRIL IN MALE BEAGLES
Okuyama, Cristina E / Mendes, Gustavo Duarte / Faro, Renato / Rezende, Vinicius M / Lagos, Rodolfo Monaco / Astigarraga, Rafael E B / Antunes, Edson / De Nucci, Gilberto | 2007
296
MORPHOLOGICAL AND FUNCTIONAL CHANGES IN P‐GLYCOPROTEIN DURING DEXAMETHASONE‐INDUCED HEPATOMEGALY
Micuda, Stanislav / Fuksa, Leos / Mundlova, Lucie / Osterreicher, Jan / Mokry, Jaroslav / Cermanova, Jolana / Brcakova, Eva / Staud, Frantisek / Pokorna, Pavla / Martinkova, Jirina | 2007
304
INHIBITION OF NAD(P)H OXIDASE REDUCES FIBRONECTIN EXPRESSION IN STROKE‐PRONE RENOVASCULAR HYPERTENSIVE RAT BRAIN
Cui, Chunmei / Chen, Alex F / Jiang, Zongpei / Wu, Qingqing / Lin, Jianwen / Wen, Hongmei / Zeng, Jinsheng | 2007
310
CALCIUM ANTAGONIST PROPERTY OF CPU228, A DOFETILIDE DERIVATIVE, CONTRIBUTES TO ITS LOW INCIDENCE OF TORSADES DE POINTES IN RABBITS
Huang, Zhi‐Jiang / Dai, De‐Zai / Li, Na / Na, Tao / Ji, Min / Dai, Yin | 2007
318
DOES NITRIC OXIDE MODULATE TRANSMITTER RELEASE AT THE MAMMALIAN NEUROMUSCULAR JUNCTION?
Nickels, Travis J / Reed, Grant W / Drummond, Justin T / Blevins, Dustin E / Lutz, Megan C / Wilson, David F | 2007
327
NITRIC OXIDE, ERECTILE DYSFUNCTION AND BETA‐BLOCKER TREATMENT (MR NOED STUDY): BENEFIT OF NEBIVOLOL VERSUS METOPROLOL IN HYPERTENSIVE MEN
Brixius, K / Middeke, M / Lichtenthal, A / Jahn, E / Schwinger, R H G | 2007
332
EFFECTS OF HYPOXIA/REPERFUSION INJURY ON DRUG DISPOSITION IN THE RAT ISOLATED PERFUSED LIVER
Arab, HA / Cheung, K / Hickman, PE / Potter, JM / Kadkhodaee, M / Roberts, MS | 2007
339
INHIBITION OF INDUCIBLE NITRIC OXIDE SYNTHASE ATTENUATES ACUTE ENDOTOXIN‐INDUCED LUNG INJURY IN RATS
Su, Chain Fa / Yang, Fwu Lin / Chen, Hsing I | 2007
347
ADMINISTRATION OF EXOGENOUS ERYTHROPOIETIN b AFFECTS LIPID PEROXIDATION AND SERUM PARAOXONASE-1 ACTIVITY AND CONCENTRATION IN PREDIALYSIS PATIENTS WITH CHRONIC RENAL DISEASE AND ANAEMIA:
Marsillach, J. / Martinez-Vea, A. / Marcas, L. / Mackness, B. / Mackness, M. / Ferre, N. / Joven, J. / Camps, J. | 2007
347
ADMINISTRATION OF EXOGENOUS ERYTHROPOIETIN β AFFECTS LIPID PEROXIDATION AND SERUM PARAOXONASE‐1 ACTIVITY AND CONCENTRATION IN PREDIALYSIS PATIENTS WITH CHRONIC RENAL DISEASE AND ANAEMIA
Marsillach, Judit / Martínez‐Vea, Albert / Marcas, Luis / Mackness, Bharti / Mackness, Michael / Ferré, Natàlia / Joven, Jorge / Camps, Jordi | 2007
350
METHODS OF ANALYSIS AND PHYSIOLOGICAL RELEVANCE OF RHYTHMS IN SYMPATHETIC NERVE DISCHARGE
Barman, Susan M / Kenney, Michael J | 2007
356
SYMPATHETIC RHYTHMS AND NERVOUS INTEGRATION
Gilbey, Michael P | 2007
362
IDENTIFICATION OF BLOOD PRESSURE CONTROL MECHANISMS BY POWER SPECTRAL ANALYSIS
Stauss, Harald M | 2007
369
DIFFERENTIAL EFFECTS OF VASOPRESSINERGIC AND OXYTOCINERGIC PRE‐AUTONOMIC NEURONS ON CIRCULATORY CONTROL: REFLEX MECHANISMS AND CHANGES DURING EXERCISE
Michelini, Lisete Compagno | 2007
377
EXERCISE TRAINING AND SYMPATHETIC NERVOUS SYSTEM ACTIVITY: EVIDENCE FOR PHYSICAL ACTIVITY DEPENDENT NEURAL PLASTICITY
Mueller, Patrick J | 2007
385
CORRIGENDUM
| 2007

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