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1.
Minerva Anestesiol ; 65(7-8): 515-20, 1999.
Article in English | MEDLINE | ID: mdl-10479838

ABSTRACT

BACKGROUND: Comparative evaluation of propacetamol and morphine on the cold restraint stress ulcers in rats. METHODS: The present study compared the effects of propacetamol hydrochloride (250 and 500 mg.kg-1 i.p.) and morphine hydrochloride (10 mg.kg-1 i.p.) against gastric mucosal damage induced by cold/restraint stress (4 degrees C for 3 h) in rats. Morphometrical and histomorphological studies were carried out. Mean ulcer number and length were calculated. RESULTS: The results show that propacetamol in the lower dose tested decreases the ulcer number and length by 56.4% (p > 0.05) and by 68.94% (p < 0.01). After propacetamol 500 mg.kg-1 the ulcer number and length were found significantly decreased by 74.83% and 83.5%. Marked decrease was found in morphine-pretreated group (-77.03% and -85.09%). The morphometrical results have been confirmed histomorphologically. CONCLUSIONS: It might be concluded that morphine (10 mg.kg-1) and propacetamol (500 mg.kg-1) are equipotent in their ability to prevent the stress ulceration in rats.


Subject(s)
Acetaminophen/analogs & derivatives , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Prodrugs/therapeutic use , Stomach Ulcer/prevention & control , Stress, Psychological/complications , Acetaminophen/therapeutic use , Animals , Cold Temperature/adverse effects , Male , Rats , Rats, Wistar , Restraint, Physical/adverse effects , Stomach Ulcer/etiology , Stomach Ulcer/pathology , Stress, Psychological/pathology
2.
Methods Find Exp Clin Pharmacol ; 20(8): 667-72, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9922982

ABSTRACT

We have studied the effect of the newly synthesized agent, roxatidine bismuth citrate (N-[3-(3-(1-piperidinyl-methyl)phenoxy)propyl]-hydroxyacetamide-2- hydroxypropane-1,2,3-tricarboxylate-bismuth(3+) complex), code name MX1, against acetylsalicylic acid (ASA)- and indomethacin-induced gastric mucosal damage in rats. Effects of MX1 (12.5, 50, 125, 184, 250 mg/kg) were compared to the effects of equimolar doses of roxatidine and bismuth subcitrate. Effect of MX1 (10(-6) M) on mucin biosynthesis measured by [3H] glucosamine incorporation in rat gastric corpus has been determined. MX1-pretreatment dose-dependently decreased the mean ulcer number and length in all doses used in an extent similar to that of roxatidine and more pronounced in comparison with bismuth subcitrate. The morphometrical results have been confirmed histomorphologically. The biosynthesis of mucin was found to be significantly enhanced after MX1 addition. The results of the present study suggest that MX1 has a gastroprotective effect against ASA- and indomethacin-induced ulcers which might be due both to its H2-blocking and mucus-stimulating activity.


Subject(s)
Anti-Ulcer Agents/therapeutic use , Organometallic Compounds/therapeutic use , Piperidines/therapeutic use , Stomach Ulcer/drug therapy , Animals , Anti-Inflammatory Agents, Non-Steroidal , Aspirin , Drug Combinations , Drug Evaluation, Preclinical , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Indomethacin , Male , Rats , Rats, Wistar , Stomach Ulcer/chemically induced
3.
J Pharm Pharmacol ; 49(8): 791-5, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9379358

ABSTRACT

We have studied the effect of the newly synthesized agent MX1, a salt of the active metabolite of the H2-blocker roxatidine with a complex of bismuth and citric acid (N-[3-(3-(1-piperidinylmethyl)phenoxy)propyl]-hydroxyacetamide+ ++ -2-hydroxypropane-1,2,3-tricarboxilate-bismuth(3+) complex), against restraint stress ulcers in rats (24 h immobilization). The effects of MX1 (12.5, 50, 125, 184 and 250 mg kg-1) were compared with the effects of equimolar doses of roxatidine (6.5, 25, 70, 100 and 140 mg kg-1) and bismuth subcitrate (6.5, 25, 70, 100 and 140 mg kg-1). The results show that MX1-pre-treatment, at all the doses used, significantly reduces the mean number and size of ulcers. Even at the lowest dose the number of ulcers was reduced by 64.3% and the size of the ulcer by 55.9%. Roxatidine (25, 70, 100 and 140 mg kg-1) dose-dependently reduces ulcer size and number by 24.6, 55.6, 85.3 and 89.0% and by (+7.2), 14.3, 57.1 and 67.9%, respectively. Bismuth subcitrate significantly reduces ulcer size and number only at the highest dose employed (-28.5 and -44.8%, respectively). The morphometric results have been confirmed histomorphologically. The results suggest that MX1 has a gastroprotective effect against stress-induced ulcers which is similar to that of the parent compound and more pronounced than that of bismuth subcitrate.


Subject(s)
Antacids/therapeutic use , Anti-Ulcer Agents/therapeutic use , Histamine H2 Antagonists/therapeutic use , Organometallic Compounds/therapeutic use , Peptic Ulcer/prevention & control , Piperidines/therapeutic use , Animals , Drug Combinations , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Male , Peptic Ulcer/etiology , Rats , Rats, Wistar , Restraint, Physical
4.
Khirurgiia (Sofiia) ; 48(3): 30-3, 1995.
Article in Bulgarian | MEDLINE | ID: mdl-8667579

ABSTRACT

The effect exerted by Hippophaë rhamnoides L. extract on the healing of experimental wounds in rats is studied histomorphologically in dynamics. The animals are divided up in three groups, as follows: group one--controls, group two--controls treated with indifferent carrier (carbopol gel), and group three--experimental, treated with carbopol gel containing extract of Hippophaë rhamnoides L. The wounds induced are standard, oval to elliptic with diameter about 3 cm. In groups I and II they are subjected to daily daubing over a 10-day period. The study of cytologic smears at 8, 24 and 48 hours, and biopsy performed on the 10th day show that in group three the epithelization is more intensive and occurs earlier, and granulation tissue differentiation (mature collagen fibers, profuse vascularity) is quicker, by comparison with groups one and two. The markedly expressed stimulating effect on the healing process is explained with the rich content of vitamins (A, C, E etc.) and microelements (sulfur, selenium, zinc, copper etc.) in the extract used.


Subject(s)
Plant Extracts/pharmacology , Skin/drug effects , Skin/injuries , Wound Healing/drug effects , Acrylic Resins , Animals , Biopsy , Disease Models, Animal , Drug Carriers , Gels , Male , Polyvinyls/pharmacology , Protease Inhibitors/pharmacology , Rats , Skin/pathology , Stimulation, Chemical , Time Factors
5.
Eksp Med Morfol ; 31(3-4): 49-60, 1993.
Article in Bulgarian | MEDLINE | ID: mdl-7805620

ABSTRACT

4-hydroxy-3-(3-oxo-1-phenyl butyl)-2H-1-benzopyran-2-one (warfarin) has been synthesised by an original method. The influence of a phase-transfer catalyst of ammonium type with alkyl substituents containing eight carbon atoms upon the reaction of Michael addition has been investigated. It has been found out that when elongating the hydrocarbon chain of the substituents to the nitrogen atom in the quaternary ammonium salt the yield of the product decreased. The acute (LD50) and subchronic (lasting for 30 days) toxicity was determined when taking warfarin orally. The experimental data show that LD50 is 500 mg/kg for mice and 420 mg/kg body mass for rats. The subchronic toxicity at experiments made with rabbits (each day taking orally respectively 25 and 100 mg/kg) does not reveal any humoral and tissue toxic influence of warfarin. The results from the comparative cytogenetic analysis of warfarin and Niffcumar are the basis of the conclusion cytogenetic analysis of warfarin and Niffcumar are the basis of the conclusion that warfarin damages chromosomes of mice's marrow cells (used as a model) less than Niffcumar. Moreover warfarin has a slight influence on these cells in the first place changing the orientation of chromosomes one towards the other and unlike other drugs it does not damage nuclear chromatin strongly.


Subject(s)
Chromosome Aberrations , Warfarin/chemical synthesis , Warfarin/toxicity , Animals , Anticoagulants/toxicity , Dose-Response Relationship, Drug , Male , Mice , Mice, Inbred BALB C , Rabbits , Rats , Rats, Wistar , Time Factors
6.
Eksp Med Morfol ; 31(3-4): 60-71, 1993.
Article in Bulgarian | MEDLINE | ID: mdl-7805621

ABSTRACT

A fructose-1,6-diphosphate preparation was tested for hepatoprotective activity through biochemical and morphologic studies in experiments on Wistar rats sustaining D-galactosamine- and paracetamole-induced hepatotoxicity. Findings indicated the modeled hepatic lesions to be readily reproducible, to simulate some characteristics of human liver pathology, and to be suitable for testing substances expected to have hepatoprotective action; intraperitoneal administration of fructose-1,6-diphosphate at a dose of 1000 mg/kg body weight proved moderately protective against liver damage by D-galactosamine; the benefit observed concerned mostly dystrophic and inflammatory changes in the liver; in a number of cases, correlation was noted between biochemical serum parameters and pathomorphologic liver alterations.


Subject(s)
Fructosediphosphates/pharmacology , Immunologic Factors/pharmacology , Liver/drug effects , Acetaminophen/toxicity , Animals , Dose-Response Relationship, Drug , Drug Interactions , Galactosamine/toxicity , Liver/metabolism , Liver/pathology , Male , Rats , Rats, Wistar
7.
Eksp Med Morfol ; 28(3): 47-50, 1989.
Article in Bulgarian | MEDLINE | ID: mdl-2806181

ABSTRACT

Some biochemical, pathohistological and ultrastructural changes in liver after the action of single intraperitoneal administration of furosemide (Furantryl-Pharmachim) in a dose of 300 mg/kg of body mass were studied in male white rats of Wistar strain. The results from the performed experiments established increased activity of serum enzymes GOT, GPT, GGT, alkaline phosphatase as well as low values of serum cholinesterase. Pathohistologic and electron microscopy examination discovered liver damage with typical congestive changes mainly--manifested local erythremia and a reduced fluid content of the blood in the liver with blockage in the sinusoidal pole of hepatocytes; there were also focal micronecrosis, considerable reduction of glycogen and slight centrolobular steatosis. The possibility is discussed for usage of hepatotoxicity, induced by furosemide, in examining the effects of some drugs with potential hepatoprotective activity.


Subject(s)
Chemical and Drug Induced Liver Injury/prevention & control , Furosemide/toxicity , Animals , Chemical and Drug Induced Liver Injury/drug therapy , Male , Rats , Rats, Inbred Strains
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