bluuebunny/crossref_metadata_2025_split huggingface dataset:
ARTERIAL AND VENOUS EFFECTS OF VERAPAMIL IN NORMAL VOLUNTEERS
Authors: THUILLEZ C. , DUHAZE P. , FOURNIER C. , LAPIERRE V. , GIUDICELLI J.‐F. 
Published: August 2009

Summary—

The effects of verapamil (120 mg orally) and a placebo on arterial pressure, heart rate, PR interval, arterial flows and diameters of the brachial and carotid arteries (pulsed Doppler technique), forearm vascular resistance, and venous diameter and compliance (cutaneous microstrain gauge and plethysmography) have been compared over a 10‐hr period in six healthy volunteers during a double‐blind and cross‐over study.
Verapamil reduced diastolic blood pressure by approximately 10 mm Hg, did not affect heart rate and increased PR interval by approximately 15%.
Verapamil significantly increased brachial and carotid arterial blood flows by 56% (P<0.01) and 16% (P<0.05), respectively, but the diameters of these vessels were not significantly modified (+ 7 and + 4%, respectively, NS). Forearm vascular resistance decreased by 40% (P<0.01), indicating that verapamil preferentially dilates small arteries. All these effects peaked at 2 h after drug intake and lasted for 6 h.
Verapamil increased hand dorsal vein diameter and flow by 95% (P<0.05) and 80% (P<0.05), respectively, from 2 to 4 h after drug intake but venous compliance, assessed by the venous diameter/venous flow ratio, was not significantly modified (from 0.71 to 0.69, NS), thus indicating that veins are not directly affected by this drug.
RELATIONSHIP BETWEEN PLASMA MEXILETINE LEVELS AT STEADY‐STATE: PRESENCE OF VENTRICULAR ARRHYTHMIAS AND SIDE EFFECTS
Authors: PEYRIEUX J.C. , BOISSEL J.P. , LEIZOROVICZ A. ,   IMPACT Research Group
Published: August 2009

Summary— The relationships between plasma mexiletine levels and the presence of ventricular arrhythmias and side effects were studied on patients from IMPACT (International Mexiletine and Placebo Antiarrhythmic Coronary Trial). 630 patients who had suffered a myocardial infarction were randomized between placebo and mexiletine.Plasma levels were measured 1 month after the beginning of treatment. Arrhythmia findings (presence or absence of premature ventricular contractions (PVCs), couplets, runs, bigeminy, trigeminy, multiformity and various combinations) were assessed from 24‐h ambulatory ECG recordings. The empirical logistic transform was used for modeling the relationships. For all these variables, except the presence of PVCs, trigeminy and runs, the association with plasma level was significant: the higher the plasma level, the lower the rate of occurrence of the particular arrhythmia. This was true whether or not the patient had the arrhythmia at baseline. Analyses based on the same model showed a significant correlation between plasma level and tremor, constipation, sexual problems and the presence of at least one side effect.As the levels of mexiletine at which side effects become frequent are in the same range as those necessary to suppress arrhythmias, the therapeutic range is narrow and individual dose adjustment should preferably be made.
ATROPINE ENHANCES NEUROMUSCULAR TRANSMISSION IN HUMANS
Authors: WALI F.A. , BRADSHAW E.G. , SUER A.H. , DARK C.H. 
Published: August 2009

Summary— The effect of atropine (1–10 μ‐kg‐1) on neuromuscular transmission in humans was studied by analysing its effects on the amplitude of indirectly‐elicited twitch (0.2 Hz) and tetanic (50 and 100 Hz for 1 s duration) contractions. Six patients, free from any neuromuscular disorders, undergoing orthopaedic surgery, were included in the present study. The patients received either no premedication or the oral benzodiazepine, temazepam, 30 mg 1–2 h pre‐operatively. Anaesthesia was induced with propofol (1–2 mg‐kg‐1, i.v., over 20 s). The patients breathed no less than 30% oxygen in nitrous oxide, halothane (1%) or enflurane (1–2%). Incremental doses of fentanyl (50–100 μ) were given to provide additional analgesia.The ulnar nerve was stimulated, supramaximally, at the wrist, and control mechanical responses of the adductor pollicis muscle, to nerve stimulation at 50 and 100 Hz for 1 s duration, were recorded. Theses responses were repeated at 2, 5 and 10 min intervals, after injection of atropine (1–10 μ‐kg‐1). At the same time, heart rate and blood pressures (systolic and diastolic) were recorded.The results showed that atropine enhanced the tetanic contractions, elicited at 50 and 100 Hz for 1 s duration, by 27 ± 1.2% (50 Hz and atropine, control 220 ± 13 g tension), and by 43 ± 7% (100 Hz and atropine, control 333 ± 26 g tension) at the 5 min intervals (mean ± S.E., n = 6). The heart rate and blood pressures were also increased, by 24 ± 2.5% (heart rate control 110±3.5 beats/min), 16±1.0% (systolic control 138±2.2 mm Hg), and 13±1.1% (diastolic control 76±1.5 mm Hg), and this precluded the use of higher doses of atropine (e.g. 1.2 mg, i.e. 20 μ‐kg‐1) in our study.The results and mechanism of action of atropine, at the neuromuscular junction, are discussed with reference to animal work, in which atropine has been shown to enhance neuromuscular transmission and/or transmitter (ACh) release, possibly by acting on muscarinic presynaptic inhibitory receptors, which are involved in the feedback mechanism of transmitter release.
COMPARATIVE EFFECTS OF ZOPICLONE, TRIAZOLAM AND PLACEBO ON MEMORY AND PSYCHOMOTOR PERFORMANCE IN HEALTHY VOLUNTEERS
Authors: WAROT D. , BENSIMON G. , DANJOU Ph. , PUECH A.J. 
Published: August 2009

Summary— This study evaluated the effects of acute doses of zopiclone (7.5 mg), triazolam (0.25 mg) and placebo on memory and psychomotor performance of 12 normal volunteers.The subjects received both drugs in a repeated measure, double‐blind Latin square design. The tests (CFF, CRT, DSST, memory assessments) were performed before and 2 and 6 hr after treatment. Zopiclone and triazolam induced an anterograde amnesia affecting short‐term and long‐term memory which lasted less than 6 hr. No retrograde amnesia was observed. Two hr after drug intake of both hypnotics psychomotor performances were significantly altered compared with placebo. The subjects also felt more drowsy, dizzy, clumsy and tired, and less alert and energetic 2 hr after zopiclone and triazolam compared to placebo. There was no difference between the effects of the two hypnotics at the doses studied.
QUANTITATIVE AUTORADIOGRAPHIC DETERMINATION OF BINDING SITES FOR A PERIPHERAL BENZODIAZEPINE LIGAND ([3H]PK 11195) IN HUMAN IRIS
Authors: VALTIER D. , MALGOURIS C. , GILBERT J.‐C. , GUICHENEY P. , UZAN A. , GUEREMY C. , Le FUR G. , SARAUX H. , MEYER P. 
Published: August 2009

Summary— Specific binding sites of peripheral‐type benzodiazepines were investigated in human iris/ciliary body (8 eyes). Examination of color‐coded prints and densitometric quantification of autoradiograms were performed on slides (20 μm) labelled with [3H]PK 11195 (1 nM) at 25°C. Nonspecific binding was determined with PK 11211 (5 μM) or Ro 5–4864 (5 μM). Binding sites were present on all the slides, with equivalent density in the 3 regions of the preparation (ciliary body, iris, and pupil margin). The numbers of binding sites in ciliary body, iris, and pupil margin, respectively, were: 42.7 ± 0.2, 30.1 ± 0.5, and 37.4 ± 0.4 femtomol/mg protein. Labelling on the pupil margin seemed to coincide with the iris sphincter muscle.The presence of peripheral benzodiazepine binding sites in iris muscular tissue, and particularly in the pupil margin, suggests that the iris preparation may be a valuable tool to detect putative physiological effects of peripheral benzodiazepines on muscular motility.
CONVERSION FROM INTRAVENOUS TO ORAL SLOW‐RELEASE DISOPYRAMIDE IN ACUTE MYOCARDIAL INFARCTION
Authors: ZANNAD F. , ROYER‐MORROT M.J. , ZAKARI I. , SADOUL N. , ROYER R.J. 
Published: August 2009

Summary— Twelve patients with acute myocardial infarction were given 1.5 mg/kg/5 min bolus + 0.4 mg/kg/hr 6 hr IV infusion of disopyramide followed by 250 mg twice daily of a slow‐release oral formulation of this drug.Plasma concentrations of total disopyramide rapidly reached steady‐state within the therapeutic margins. The plasma steady‐state concentrations of the major metabolite mono‐N‐dealkyl‐disopyramide (MND) showed large intra‐individual variations. There was no correlation between plasma levels of either disopyramide or MND and the occurrence of anticholinergic side effects. The drug had no significant effect on mean blood pressure, heart rate, or ECG intervals.This therapeutic regimen, including conversion from the IV form to oral slow‐release tablets, could be recommended in myocardial infarction.
EFFECTS OF PROGESTOGENS ON LIPEMIA AND LIPOLYSIS IN RAT: EFFECTS OF PROGESTERONE, MEGESTROL ACETATE, NORETHINDRONE ACETATE, AND NOMEGESTROL ACETATE
Authors: HAZARD M.‐C. , CLAVET M. , CHAPIGNAC A. , PARIS J. 
Published: August 2009

Summary— Effects of 4 progestogens at equal dosages (5 mg/kg/day) on lipid metabolism and plasma glucose levels of adult female rats were compared. The 4 progestogens studied were progesterone (P) by SC injection, and megestrol acetate (MEG), norethindrone acetate (NOR), and nomegestrol acetate (NOM) PO.MEG, a 17α‐hydroxyprogesterone derivative, induced significant increases in glucose, total and high‐density lipid (HDL) cholesterol, triglyceride, and phospholipid plasma levels. Treatment with NOR, a 19‐nortestosterone derivative, resulted in a reduced gain in body wt and in a marked decrease in all plasma lipid parameters. The 19‐norprogesterone derivative NOM, like P, did not alter lipid or glucose metabolism, despite a significant increase in body wt gain. In particular, no reduction in the HDL cholesterol level occurred. Plasma and tissue lipolytic activities remained unchanged.The results of this study confirm interest in the therapeutic class of 19‐norprogesterone‐derived progestogens, exemplified by NOM, with respect to their lack of metabolic side effects.
L‐ARGININE METHYLESTER REDUCES Ca2+/Cl− ‐DEPENDENT L‐[3H]GLUTAMATE BINDING AND Ca2+‐ACTIVATED NEUTRAL PROTEASE ACTIVITY IN RAT HIPPOCAMPAL MEMBRANES
Authors: BENNARDINI F. , FAILLI P. , MATUCCI R. , BARTOLINI A. , MALCANGIO M. , MASSARI M. , FRANCONI F. , GIOTTI A. 
Published: August 2009

Summary— Specific binding of L‐[3H]glutamate was measured in Tris‐HCl buffer in rat hippocampal membranes. In these experimental conditions 1 mM CaCl2 induced an increase in binding due to an increase in Bmax.L‐Arginine methylester did not modify the Cl−‐dependent binding of L‐[3H]glutamate, but it decreased Ca2+ /Cl− ‐stimulated binding in a dose‐dependent manner, decreasing Bmax without changing KD. L‐Arginine methylester reduced calcium‐activated neutral protease activity in a dose‐dependent manner. Serine protease inhibitors (aprotinin and di‐isopropylfluorophosphate) did not affect L‐[3H]glutamate binding, whereas leupeptin reduced it in a dose‐dependent manner. L‐Arginine did not mimic the effect of L‐arginine methylester in either model.
EFFECTS OF VARIOUS PHARMACOLOGICAL AGENTS ON ISOLATED HUMAN BRONCHIAL AND PULMONARY ARTERIAL AND VENOUS MUSCLE PREPARATIONS CONTRACTED BY LEUKOTRIENE D4
Authors: BOURDILLAT B. , HAYE‐LEGRAND I. , LABAT C. , RAFFESTIN B. , NOREL X. , BENVENISTE J. , BRINK C. 
Published: August 2009

Summary—The response of isolated human bronchial muscle preparations to leukotriene D4(LTD4, 0.1 μM; 0.22 ± 0.03 g/mm2) was similar to that of histamine (50 μM; 0.21 ± 0.02 g/mm2). Isolated pulmonary venous preparations also contracted to these same concentrations of both agonists (LTD4, 0.32±0.19 g/mm2; and histamine, 0.36±0.07 g/mm2). However, pulmonary arterial preparations responded to histamine (50 μM, 0.59±0.10 g/mm2) but exhibited a reduced response to LTD4(0.3 μM, 0.06 ± 0.01 g/mm2). Bronchial and pulmonary venous muscle preparations from the human lung had the same sensitivities to LTD4(pD2values: bronchus, 7.95±0.08 and vein, 7.76±0.07). When bronchial or pulmonary venous muscle preparations were incubated for 30 min with either diltiazem (10μM), indome‐thacin (1.7 μM) or L‐cysteine (3 μM), the LTD4cumulative concentration‐effect curves following these drug treatments were similar to controls. However, FPL‐55712 (10 μM) significantly shifted the LTD4concentration‐effect curves produced in bronchial preparations to the right. In isolated pulmonary arterial preparations none of these drug treatments enhanced the LTD4response.These results show that isolated human pulmonary arterial preparations are less responsive to LTD4than bronchial or venous preparations. In addition, the data obtained subsequent to the various drug treatments indirectly suggest that the LTD4contraction is not modified by a calcium channel blocker or by inhibition of the endogenous products of the cyclooxygenase pathway.
STUDY OF DRUG CONSUMPTION IN A WORKING ENVIRONMENT IN FRANCE
Authors: BANCAREL Y. , BLANC M.P. , CHARRIN G. , CHASTAN E. , COLDEFY J.F. , COTTES L. , DUCAP A. , EVRARD P. , GALIAY C. , GUIRAUD J.C. , HOTELIER G. , GARCIA G. , JANSOU P. , FERREIRA D. , LOUIS A. , MARTIN F. , MONTASTRUC N. , SARDA R. , SAINT‐PIERRE Y. , MONTASTRUC J.L. 
Published: August 2009

Summary— 1. The present study was conducted to investigate drug consumption in a working environment by means of an anonymous questionnaire given to 2221 subjects and answered in the presence of the work physician.2. Among the 2221 subjects, 922 had taken at least 1 drug during the week just preceding the medical visit to the company.3. Women used significantly more hypnotics, sedatives, analgesics, and endocrinologic drugs and homeopathic agents than men, who tended to take more respiratory drugs.4. Consumption of drugs significantly increased with age.5. The mean value of estimated difficulty of work was higher in subjects taking drugs in general, as well as hypnotics, sedatives, analgesics, anti‐inflammatory agents and gastrointestinal drugs. There was a significant relationship between difficulty of work and total number of medicines taken.6. Manual workers in general, took no more drugs than nonmanual workers, except for analgesics, anti‐inflammatory drugs, and antibiotics. Nonmanual workers used homeopathy more than manual workers.7. The presence of extraprofessional problems was associated with an increase in drug consumption.
LIMITATIONS OF THE BENZODIAZEPINE RECEPTOR NOMENCLATURE: A PROPOSAL FOR A PHARMACOLOGICAL CLASSIFICATION AS OMEGA RECEPTOR SUBTYPES
Authors: LANGER S.Z. , ARBILLA S. 
Published: August 2009

Summary—At present, the nomenclature of benzodiazepine (BZ) receptors is based on historical association with the BZ structure. However, it is mainly through the new compounds chemically unrelated to BZ that the central and peripheral subtypes of BZ receptors have been characterized. We therefore propose the nomenclature of a Greek letter omega, as ω1, ω2, and ω3to designate the central BZ1, BZ2, and peripheral BZ receptors, respectively. Among the several classes of non‐BZD drugs with affinity for different receptors, the imidazopyridines provide a valuable tool for the characterization of omega receptor subtypes.Most BZ are nonselective ligands for the central ω1and ω2receptors, while selectivity for ω1receptor subtypes is present in several non BZ chemical series: imidazopyridines (zolpidem), triazolopyridazines (CL 218872), betacarbolines (β‐CCE), and pyrazoloquinolines (CGS 8216). Selective ligands for the ω2subtype are not available so far.The so‐called peripheral BZ receptor is also present in the central nervous system; therefore, the proposed nomenclature of ω3receptors resolves this paradox because it does not designate location and is defined in terms of pharmacological specificity. Selective ligands for ω3receptors include the BZ Ro 5–4864, and the isoquinolinecarboxamide PK 11195, while the imidazopyridine alpidem is the ligand with the highest affinity for this receptor subtype.
ARE THERE CIRCADIAN AND CIRCANNUAL VARIATIONS IN ACUTE TOXICITY OF PHENOBARBITAL IN MICE?
Authors: BRUGUEROLLE B. , PRAT M. , DOUYLLIEZ C. , DORFMAN P. 
Published: August 2009

Summary— The present work aims to document the possible influence of the time of the year on the circadian pattern of phenobarbital acute toxicity in mice by determination of phenobarbital acute toxicity at four different months of the year (i.e. October, January, April, and July).Our data indicate an important variation of phenobarbital acute toxicity throughout the year, with the maximum mortality occuring in January (i.e. minimum LD50) the minimum in July (i.e. maximum LD50). Thus, the season, not often taken into account, is an important determinant in toxicological studies.
ENHANCEMENT OF ANTIBODY RESPONSE AND DELAYED‐TYPE HYPERSENSITIVITY BY THALIDOMIDE IN MICE
Authors: DESCOTES J. , TEDONE R. , EVREUX J.‐C. 
Published: August 2009

Summary— Renewed interest in thalidomide stemmed from the suggestion by several authors that it might prove useful against immune‐related diseases. Despite interesting preliminary findings, little is actually known regarding its immunoenhancing properties in vivo.Male and female Swiss mice, aged 6–8 wk, were given 0.5 or 25 mg/kg/day of thalidomide orally for 4 wk. Various immunological parameters were then assessed. When compared to controls, mice exposed to the higher dose presented with a significantly increased thymus weight index, whereas spleen weight index remained unchanged. Anti‐sheep erythrocyte plaque‐forming cells and hemagglutinin titers were increased by 44% and 29%, respectively. Contact hypersensitivity to picryl chloride was enhanced by 62%. Finally, colloidal carbon clearance was not altered. Interestingly, the lower dose (5 mg/kg/day) exerted no effect whatsoever.
CHARACTERIZATION OF β‐ADRENOCEPTORS IN MYOMETRIUM OF PREPARTURIENT RATS
Authors: MALTIER J.P. , LEGRAND C. 
Published: August 2009

Summary—The purpose of this study was to characterize the β‐adrenoceptor subtypes in pregnant rat myometrial membrane fractions and to determine the concentration of β2‐adrenoceptors in uterus during late pregnancy. Two methods are compared. A non‐subtype‐selective antagonist radioligand β‐[3H]dihydroalprenolol ([3H]DHA) was used to label all of the β‐adrenoceptors. [3H]DHA bound to both β1‐ and β2‐adrenoceptors with indistinguishable affinity (KD= 1.31 nM, Bmax= 174 fmol/mg protein). Computer modelling of competition curves of unlabeled selective antagonists or agonists was then required in order to determine reliably β1‐ and β2‐adrenoceptor affinities and proportions: the β2‐adrenoceptors represent 35.5% and the β2‐adrenoceptors 64.5% of the entire β‐adrenoceptor population in rat gravid myometrium at term.The second approach utilized the radioligand [3H]hydroxybenzylisoproterenol ([3H]HBI) which is a very high‐affinity β‐adrenoceptor agonist. The characteristics of the (3H)HBI binding sites are essentially those expected of β2‐adrenoceptors, but the [3H]HBI binding sites represent only 34% of [3H]DHA binding sites and may represent the fraction of β2‐adrenoceptors that mediate adenylate cyclase stimulation and uterine relaxation.Between 21 d 09 h and 22 d 09 h of gestation, the number of β2‐adrenoceptors was constant (mean = 225.6±20.2 fmol/mg protein). At term, the number of [3H]HBI binding sites dropped (‐75%) during the last 7 h of pregnancy, suggesting a reduced ability to elicit relaxation through β‐adrenoceptor activation in parturient myometrium of rat.
EVALUATION OF THE NATRIURETIC AND BETA‐ADRENOCEPTOR‐BLOCKING EFFECTS OF TIENOXOLOL IN NORMAL VOLUNTEERS
Authors: BERDEAUX A. , LOUESLATI E. , GERARD J.L. , PUSSARD E. , GIUDICELLI J.F. 
Published: August 2009

Summary— The beta‐adrenoceptor blocking and diuretic properties of tienoxolol (150 mg and 300 mg) were investigated and compared to those of a placebo in a double‐blind, cross‐over trial in six healthy volunteers. Heart rate (HR), systolic and diastolic blood pressures, peak expiratory flow rate (PEFR) at rest and during vigorous exercise, plasma renin activity (PRA) and aldosterone levels at rest, and diuresis and urinary electrolyte excretion values were measured before and at intervals up to 24 h after oral administration of the drugs. In addition, the clearances of electrolytes, uric acid, and creatinine were calculated, as well as the fractional sodium excretion (Fe Na%) before and 4 h and 24 h after drug intake. Finally, tienoxolol plasma levels were measured.Tienoxolol significantly and dose‐dependently reduced exercise‐induced tachycardia. This effect started 1 h after drug administration, peaked between 4 h and 6 h (‐ 12% and ‐ 17% from control values at 150 mg and 300 mg, respectively), and lasted at least 12 h. Resting HR was decreased at 300 mg (P<0.05), PRA was decreased at both doses (P<0.05), but PEFR was not drug‐affected. 24‐h cumulative sodium excretion was increased (+ 24% at 150 mg [NS], +38% at 300 mg [P<0.01]) as compared to placebo, and Fe Na% did not change, regardless of the dose administered. 24‐h cumulative diuresis was moderately increased by tienoxolol (NS), whereas creatinine clearance rose after the 300‐mg dose, suggesting that tienoxolol might increase glomerular filtration rate. Plasma aldosterone levels remained unchanged. Finally, the elimination half‐life of tienoxolol was 7.5 h.Thus, in healthy volunteers, tienoxolol behaves as an early acting and relatively long‐lasting selective beta1‐adrenoceptor blocking drug endowed with significant natriuretic properties.
SINGLE‐DOSE PHARMACOKINETICS OF AMINEPTINE AND OF ITS MAIN METABOLITE IN HEALTHY YOUNG ADULTS
Authors: LACHATRE G. , PIVA C. , RICHE C. , DUMONT D. , DEFRANCE R. , MOCAER E. , NICOT G. 
Published: August 2009

Summary— The pharmacokinetics of the tricyclic antidepressant amineptine (Survector®) and its main metabolite were studied in 12 young healthy adults (6 men, 6 women; mean age 35.8 yr). Plasma samples were taken over 24 h following a single oral dose of 100 mg amineptine chloryhdrate. Plasma levels of both compounds were determined by means of high performance liquid chromatography.Amineptine was rapidly absorbed. Mean peak plasma concentrations of amineptine and its metabolite occurred 1 h and 1.5 h, respectively, after product administration. The mean apparent volume of distribution was large: 2.4 l.kg−1. Elimination was rapid; the mean half‐lives of the 2 compounds were short: 0.8 h for amineptine and 2.5 h for the metabolite. The mean apparent plasma clearance of amineptine was high (124.8 l.h−1).When the results were adjusted for body weight and surface area, no significant difference in pharmacokinetic parameters was found between men and women.Given its pharmacokinetic characteristics there is no risk of amineptine accumulation and thus it is a particularly easy drug to manage.A standard dosage of amineptine was defined for use in healthy young adults.
PREVENTION OF CCL4‐INDUCED LIVER CIRRHOSIS BY SILYMARIN
Authors: MOURELLE M. , MURIEL P. , FAVARI L. , FRANCO T. 
Published: August 2009

Summary—The efficacy of silymarin treatment in preventing biochemical and histological alterations in CCl4‐induced liver cirrhosis in rats was studied. Four groups of rats were treated with: (1) CCl4; (2) mineral oil; (3) CCl4+ silymarin; and (4) silymarin. All animals were sacrificed 72 h after the end of treatments. The activities of alkaline phosphatase (alk. phosp.), gamma‐glutamyl transpeptidase (GGTP), glutamic pyruvic transaminase (GPT) and glucose‐6‐phosphatase (G6Pase), and bilirubin content were determined in serum. Na+, K+‐ATPase and Ca++‐ATPase activities were measured in isolated plasma membranes. Lipoperoxidation, triglycerides (TG), and glycogen contents were also measured in liver homogenates.Liver cirrhosis was evidenced by significant increases in liver collagen, lipoperoxidation, serum activities of alk. phosp., GGTP, GPT, G6Pase, bilirubin content, and liver TG.Activities of ATPases determined in plasma membranes were significantly reduced, as was liver glycogen content. Silymarin cotreatment (50 mg/kg b.wt) completely prevented all the changes observed in CCl4‐cirrhotic rats, except for liver collagen content which was reduced only 30% as compared to CCl4‐cirrhotic rats. Silymarin protection can be attributed to the agent's antioxidant and membrane‐stabilizing actions.