PubMed Health⌕ Search

Biomedical subjects

T Stoytchev

Publications and source records attributed to T Stoytchev.

At least 19 recordsLinked to original sources
PubMed1999

Combined effect of propranolol with nifedipine or with diltiazem on rat liver monooxygenase activities.

The effects of two Ca2+ antagonists nifedipine (NF) and diltiazem (DL) and of the nonselective beta-adrenergic blocking agent propranolol (PR) on the hexobarbital (HB) sleeping time and on the activity of some liver drug-metabolizing enzyme systems in male Wistar rats were studied. Two h after single oral administration PR (50 mg/kg) did not change HB sleeping time, while NF (50 mg/kg) and DL (30 mg/kg) prolonged it by 171.2 and 99.6%, respectively. Coadmistration of PR with DL or with NF significantly prolonged HB sleep by 240.7 and 129%, respectively. Only NF increased aniline 4-hidroxylase (AH) activity (by 92%) and the total P-450 content (by 24%). PR and NF increased cytochrome b5 content and this effect was also observed with the combinations PR + NF (by 109%) and PR + DL (by 102%). The NADPH cytochrome P-450 reductase activity was significantly decreased by NF and DL and after their combination with PR. The ethymorphine-N-demethylase (EMND) and amidopyrine-N-demethylase (APND) activities were not changed. The effects of PR, NF and DL administrated alone or in combination on liver oxidative metabolism are considered as possible mechanisms of drug interactions.

Adrenergic beta-Antagonists↗
PubMed1997

Influence of hydrocortisone on the analgesic effect, toxicity and metabolism of aspirin in mice.

1. Hydrocortisone (HC; 80 mg/kg body weight, intraperitoneally for 4 days), both alone and in combination with acetylsalicylic acid (ASA; 160 mg/kg body weight, orally, for 4 days), decreased ASA general and specific toxicity via metabolic modulation of drug-metabolizing enzyme systems (intestinal ASA-esterase and hepatic UDP-glucuronyltransferase) and did not change the ASA analgesic effect. 2. ASA alone, given 4 for days, did not change the specific ASA toxicity, but increased its general acute toxicity, which was probably due to alterations in some intestinal and hepatic metabolizing enzyme systems.

Animals↗
PubMed1994

Liver enzyme activities after multiple administration of nifedipine in mice.

The effect of multiple nifedipine administration on hexobarbital sleeping time, liver monooxygenase and synthetase activities, lipid peroxidation and microsomal membrane fluidity were studied in male albino mice. The drug was administered orally at a dose of 25 mg/kg daily for 14 and 21 days. Nifedipine caused enzyme induction, demonstrated by shortened hexobarbital sleeping time, enhanced ethylmorphine N-demethylase, aniline 4-hydroxylase, ethoxycoumarine O-deethylase, UDP-glucuronyl transferase, glutathione S-transferase and NADPH-cytochrome c reductase activities and increased content of cytochrome P450 and cytochrome b5. This effect persisted until the 7th day after the last dose of nifedipine. There were no changes in lipid peroxidation and fluidity of the microsomal membranes after 14-day nifedipine administration. The increased cytochrome P450 content and drug metabolizing enzyme activities could be not associated with changes in these liver microsomal membrane properties.

Administration, Oral↗
PubMed1993

On the enzyme-inducing action of calcium antagonists.

The effects of three calcium antagonists, nifedipine (NF), verapamil (V) and diltiazem (DL), on rat liver monooxygenases were studied. The drugs were administered in oral doses of 50, 40 and 30 mg/kg daily for 3 weeks in male Wistar rats. NF and V shortened the hexobarbital (HB) sleeping time and increased benzphetamin-N-demethylase (BND), ethylmorphine-N-demethylase (EMND), aniline hydroxylase (AH), ethoxycoumarine-O-deethylase (ECOD), ethoxyresorufin-O-deethylase (EROD) and NADPH-cytochrome c reductase activities and the content of cytochrome P-450 and microsomal heme, but did not change the content of cytochrome b5. The data suggest that these calcium antagonists exert an enzyme-inducing effect on the hepatic monooxygenases. DL significantly increased only the EROD and NADPH-cytochrome c reductase activities and shortened HB sleeping time to a lesser extent, suggesting a weaker enzyme-inducing effect as compared to NF and V. The three drugs increased the delta-aminolevulinic acid (ALA) synthetase activity and decreased heme oxygenase (HO) activity. The increased cytochrome P-450 content is probably due to the increased synthesis and the decreased breakdown of this hemoprotein.

5-Aminolevulinate Synthetase↗
PubMed1993

Effects of propranolol, pindolol and atenolol after multiple administration in rats on the duration of hexobarbital sleeping time and on the activity of some drug-metabolizing enzyme systems.

Three beta-adrenergic blocking agents propranolol (50 mg/kg), pindolol (5mg/kg) and atenolol (150mg/kg) were administered orally in rats for 21 days. The duration of hexobarbital (HB) sleeping time and the activities of some liver monooxygenases and synthetases were studied. The HB sleeping time was not changed. Propranolol and pindolol decreased the ethylmorfin-N-demethylase (EMND) and benzphetamine-N-demethylase (BND) activities. The three beta-adrenergic blocking agents did not change the activities of anilinehydroxylase (AH), ethoxycoumarine-O-demethylase (ECOD), and glutathione-S-transferase (G-S-T), the total content of cytochrome P-450, b5 and microsomal heme. They increased the activities of uridinediphosphoglucuronil transferase (UDPGT) and NADPH-cytochrome C reductase. The participation of different mechanisms of the effects of the three beta-adrenergic blocking agents on the activity of drug-metabolizing enzyme systems was discussed.

Animals↗
PubMed1991

Effect of continuous treatment with some heavy metal salts upon rat hepatic monooxygenases.

The effect of 90-days treatment with Co(NO3)2, NiSO4, CdSO4, ZnSO4 and HgCL2 on the rat liver cytochrome P-450 linked monooxygenases was studied. It was found that all metal salts studied significantly decreased the activity of ethylmorphine N-demethylase in the rat liver. The activity of benzphetamine N-demethylase was decreased by the salts of Co, Cd and Zn whereas Hg and Ni did not change it. Hepatic microsomal cytochrome P-450 content was significantly decreased after treatment with Co, Cd, Zn and Ni and was not changed by Hg. Microsomal hem content was decreased by Co, Cd and Zn and was not changed by Ni and Hg. Co, Cd, Zn and Ni salts decreased the activity of 5-aminolevulinic acid synthetase which shows that the decreased cytochrome P-450 content was probably due to a decrease of its synthesis. HgCL2 had no enzyme inhibitory effect. All metal salts did not change the metabolizing activity of aniline hydroxylase which confirm that multiple molecule species of cytochrome P-450 exist in the liver of adult rats. The hepatic cytochrome b5 content was not changed by the metal salts studied which shows that probably cytochrome b5 was not involved in the enzyme inhibitory action of heavy metal salts on the rat liver monooxygenases.

5-Aminolevulinate Synthetase↗
PubMed1990

Liver monooxygenase activity after multiple application of nifedipin, verapamil and diltiazem.

The effects of three calcium antagonists--nifedipin (NF), verapamil (V) and diltiazem (DL)--on the duration of hexobarbital (HB) sleeping time and on monooxygenase activity are studied. The drugs are applied in oral doses of 50, 40 and 30 mg/kg, respectively every day for 3 weeks on male albino rats. NF was found to shorten the duration of HB sleep, to increase the activities of EMD, BPD, AH, ECOD, EROD, NADPH-cytochtome P-450 reductase and the content of cytochrome P-450, and it does not change significantly the content of cytochrome b 5. It increases AD hydroxylation in positions 7-alpha-, 16-beta-, 16-alpha- and 6-beta, which suggests indirectly that NF has probably induced the synthesis of cytochrome P-450a, cytochrome P-450b, cytochrome P-450h and cytochrome P-450p, respectively. Verapamil also shortens the duration of HB sleeping time, increases the activities of EMD, BPD, AH, EROD and NADPH-cytochrome P-450 reductase, not changing the cytochrome P-450 content and the ECOD activity. It increases AD hydroxylation in positions 7-alpha- and 16-alpha-, which suggests probable induction of the synthesis of cytochrome P-450a and cytochrome P-450h. Unlike the other two calcium antagonists, diltiazem slightly shortens the duration of HB sleeping, not changing the enzyme activities studied, the content of cytochrome P-450 and cytochrome b 5, but increases the activities of EROD and NADPH-cytocrome P-450 reductase. It increases AD hydroxylation in positions 7-alpha-, 16-alpha- and 6-beta, which suggests probable induction of cytochrome P-450a, cytochrome P-450h and cytochrome P-450p.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenedione↗
PubMed1990

Effect of potassium ethylxanthogenate on the acetaminophen hepatotoxicity in mice.

The effects of potassium ethylxanthogenate (PEX), acetaminophen (AAP) and their combination on the activity of serum transaminases, liver glutathione level and the activity of some drug metabolizing enzyme systems in male albino mice are studied. PEX (80 mg/kg p. o.), applied one hour before AAP (737.5 mg/kg p. o.) or simultaneously with it, prevents the AAP-induced rise in transaminases. PEX reduces significantly the AAP-induced depletion of the liver glutathione. Eighteen hours after the administration of a hepatotoxic dose of AAP, there is a statistically significant decrease of the activity of aniline hydroxylase, ethylmorphine demethylase, uridine diphosphoglucuronyl transferase, glutathione-S-transferase, NADPH-cytochrome-c-reductase, the P-450 content and a 5-fold increase of TBA-reactive products. PEX, introduced one hour before AAP or simultaneously with it, prevents these changes. The basic mechanism through which PEX reduces the liver toxicity of AAP is assumed to be the decrease in the amount of toxic metabolite formed.

Acetaminophen↗
PubMed1990

Effect of subchronic treatment with some heavy metal salts on the activity of the drug metabolizing enzyme system in female rats.

In experiments on female albino rats the effect of 30-day treatment with salts of Co, Cd, Ni, Zn and Hg on the liver monooxygenase system was studied. It was found that CdCl2 and HgCl2 significantly decreased the activity of aniline hydroxylase whereas the activity of ethylmorphine-N-demethylase tended to remain almost constant and no significant changes were observed. The cytochrome P-450 level in Zn-treated female rats was decreased while the other metal salts did not change it. The cytochrome b5 levels were relatively stable and there were no significant differences between treated and untreated animals. Co, Cd and Hg decreased the NADPH-dependent lipid peroxidation whereas Ni and Zn did not change it. All metal salts caused no marked alterations in the female rat liver microsomal membrane fluidity.

Animals↗
PubMed1990

The effect of alloxan diabetes on the activity of some mixed function oxidases in male rats.

The effect of alloxan-induced diabetes on the duration of hexobarbital sleep (HB sleep) the activity of ethylmorphine-N-demethylase (EMND), aniline hydroxylase (AH), the content of microsomal cytochrome P-450 and b5, on the activity of ethoxycumarine-0-deethylase (ECOD) and ethoxyresorufine-0-deethylase (EROD) after induction with beta naphthoflavone (beta-NF), as well as the activity of benzphetamine-N-demethylase and pentoxyresorufine-O-dealkylase (PROD) after induction with phenobarbital (PB), was studied in experiments on male Wistar rats. In rats with alloxan diabetes there was a significant prolongation of HB sleep (by 106%) and inhibition of the liver EMND (by 54%), while the AH activity increased by 131%, with a parallel rise in the content of microsomal cytochromes P-450 (by 67%) and b5 (by 113%). In rats with alloxan diabetes the enzyme-inducing effect of beta-NF with respect to the activities of EROD and ECOD is reduced, although diabetes by itself causes a rise in the ECOD activity in untreated animals. When induced with PB, the PROD and benzphetamine-N-demethylase activity in diabetic rats is lower than in the healthy animals. However, if the enzyme activity after the application of inducers is referred to the respective starting enzyme activities of the two groups of animals, it is found that the enzyme-inducing effect of PB is preserved and even slightly potentiated in the diabetic rats compared with the healthy ones: the increases in the benzphetamine-N-demethylase activity is by 60% in the diabetic rats, compared with a rise of 28% in the healthy animals, of the PROD activity 19 times for the diabetic compared with 16 times increase for the healthy rats.

Animals↗
PubMed1989

Effect of potassium ethylxanthogenate on the toxicity and analgesic effect of acetaminophen.

The effect of potassium ethylxanthogenate (PEX) on the toxicity and the analgesic effect of acetaminophen (AAP) were investigated on male albino mice. PEX in a dose of 80 mg/kg body weight, administered subcutaneously or orally one hour before AAP, or simultaneously with it, induces prolongation of the survival of the experimental animals and increases LD50 of AAP. The protective effect of PEX (s.c. and p.o.) is more pronounced when this agent is introduced one hour before AAP (i.p. and p.o.), compared with the simultaneous administration, and when it is applied orally, compared with the subcutaneous administration. The average lethal dose of the combination (AAP p.o. + PEX p.o. 1 hour previously) increases 2.57 times after observation for 7 days, compared with that of AAP. Although it does not possess its own analgesic effect, PEX potentiates the analgesic effect of AAP (which is more pronounced for the low AAP doses) and reduces its average effective dose. After 14-day administration, AAP potentiates its own analgesic effect in the lower doses. The potentiating effect of PEX on the analgesic effect of AAP is similar on the first and on the 14th day of the treatment. The principal mechanism through which PEX decreases the toxicity and potentiates the analgesic effect of AAP is assumed to be the inhibition of its metabolism by inhibition of the cytochrome P-450-linked monooxygenases, not ruling out the possibility of a certain effect on the AAP absorption.

Acetaminophen↗
PubMed1989

Effect of desoxycorticosterone on the activity of drug-metabolizing enzyme systems.

Single administration of desoxycorticosterone acetate (DOCA) in a dose of 50 mg/kg body mass intramuscularly in male Wistar rats revealed dose-dependent potentiation of hexobarbital sleeping time and inhibition of the activity of the oxidases with mixed functions in substrates of types I (hexobarbital, ethylmorphine) and II (aniline), although this is not accompanied by changes in the components of the electron-transport chain. It is assumed that DOCA may possibly inhibit the metabolism of the above mentioned substrates, being an alternative substrate of oxidases with mixed functions. In an acute experiment DOCA does not influence the activity of esterases (liver esterase A and intestinal esterase B), but the compound has an inhibitory effect on some synthetase reactions--cytosol glutathione-S-transferase. Repeated administration of DOCA for 3-27 days in doses of 10 and 20 mg/kg i.m. does not have an enzyme-inducing effect. There are no significant changes in the oxidases with mixed functions and in the content of cytochrome P-450. The effects of DOCA on drug metabolism after a single and after repeated application are compared with the effects of hydrocortisone.

Animals↗
PubMed1986

Toxic and protective effects of antioxidants in biomembranes.

Natural and synthetic antioxidants (AOs) are widely used as stabilizers of biomembranes against lipid peroxidation (LPO). Natural AOs (tocopherols, ubiquinols) containing hydrocarbon "tails" do not disturb the membrane lipid bilayer. Synthetic AOs devoid of hydrocarbon radicals may perturb the lipid bilayer. It was shown that AOs devoid of hydrocarbon tails (butylated hydroxytoluene, 2,2,5,7,8-pentamethyl-6-hydroxychromane) exerted toxic effects on erythrocyte membranes (induced hemolysis), on sarcoplasmic reticulum membranes (inhibited Ca2+-transport) and on platelet membranes (initiated Ca2+-dependent aggregation) in vitro. These AOs are the substrates of cytochrome P-450, and underwent oxidative hydroxylation. This suggests that they have short half-life times in biomembranes and in the organism. Antioxidants with hydrocarbon tails, are hydroxylated at very low rates and are slowly excreted. Antioxidants devoid of hydrocarbon tails, are 10-20 fold more potent LPO inhibitors than the corresponding AOs with hydrocarbon tails. The strategy of AOs application for long and short-term stabilization of biomembranes against LPO in vivo is discussed.

Animals↗
PubMed1985

Effect of some heavy metal salts on hepatic monooxygenases after subchronic exposure.

The effects of subchronic exposure of some heavy metal salts on the activity of the rat liver monooxygenases and NADPH-dependent lipid peroxidation have been studied. The salts of Co, Cd and Zn (when given repeatedly for one month in subtoxic doses) shortened the duration of hexobarbital sleeping time, increased the activities of Ethylmorphine-N-demethylase (EMD) and Benzphetamine-N-demethylase (BND), and the cytochrome P-450 and heme contents. The same metal salts increased the activity of delta-aminolevulinic acid synthetase (ALAS), decreased that of Heme-oxygenase and decreased NADPH-dependent lipid peroxidation. Whereas the salts of Co, Cd and Zn seem to exert an enzyme-inducing action on the mixed function oxidizing enzyme systems, the salts of Hg and Ni did not show such effects.

5-Aminolevulinate Synthetase↗
PubMed1985

On the mechanism of the enzyme-inducing action of some heavy metal salts.

The effect of Co(NO3)2, CdSO4, NiSO4, ZnSO4, and HgCl2 (given repeatedly in subtoxic doses in the drinking water for 30 days) on rat liver monooxygenases was studied in experiments on male Wistar rats. The salts of Co, Cd, and Zn increased the activity of benzphetamine-N-demethylase, the content of cytochrome P-450 and microsomal heme. The data suggest that these salts exert an enzyme-inducing effect on the hepatic monooxygenases. The same metal salts (Co, Cd, and Zn) increased the activity of delta-aminolevulinic acid (ALA) synthetase and decreased that of heme oxygenase. The increased cytochrome P-450 content is probably due to the increased synthesis and the decreased breakdown of this hemoprotein. HgCl2 and NiSO4 did not exert an enzyme-inducing action. The lack of change in the activity of NADPH-cytochrome c reductase and cytochrome b5 (except for ZnSO4) suggests that these components of the electron transport chain are not likely to be involved in the enzyme-inducing action of the heavy metal salts.

5-Aminolevulinate Synthetase↗
PubMed1985

Epileptogenic effect of intracortically applied kainic acid in cats.

The effect of two doses (5 micrograms/microliters) of kainic acid (KA) injected intracortically into the posterior lateral gyrus of cats was investigated. KA in a dose of 5 micrograms/microliters provoked cortical epileptogenic focus 8-12 min after its application, developing later into a focal seizure. Administration of 10 micrograms/microliters KA resulted after 15-20 sec in paroxysmal discharges of spikes and sharp-slow waves at the site of the application, which propagated ipsilaterally. Thereafter the paroxysmal activity spread contralaterally, became generalized and developed into an epileptic state. The effect of KA was considered to be a dose-dependent one. N-Aminomethylpiperazine-3, 3-diethyl-2, 4-pyridinedione (DKMP) in a dose of 100 mg/kg injected i.v. on the background of developed epileptic state exerted a rapid inhibitory effect of 60-100 min duration on the paroxysmal activity. employed as a model of secondary generalized focal epilepsy.

Animals↗