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L Benes

Publications and source records attributed to L Benes.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of cumene hydroperoxide-induced lipid peroxidation by a novel pyridoindole antioxidant in rat liver microsomes.

The ability of stobadine, a novel pyridoindole antioxidant, to inhibit lipid peroxidation induced by cumene hydroperoxide was investigated in rat liver microsomes. In the micromolar range stobadine effectively inhibited lipid peroxidation as measured by the formation of thiobarbituric acid reactive products. The peroxidation-related degradation of microsomal cytochrome P-450 was prevented by stobadine in the same pattern. Another line of evidence in support of the antioxidant action of stobadine was given by its inhibition of cumene hydroperoxide-induced oxygen consumption in microsomal incubations. Inhibition of lipid peroxidation was not a function of decreased bioactivation of cumene hydroperoxide, as stobadine did not affect the rate of cytochrome P-450 dependent cleavage of cumene hydroperoxide. Neither had stobadine any effect on cytochrome P-450 peroxidase function characterized by the rate of cumene hydroperoxide-dependent oxidation of TMPD, and no direct spectral interaction with microsomal cytochrome P-450 was observed in the micromolar region. We suggest that it is the ability of stobadine to scavenge alkoxyl and peroxyl radicals that is predominantly responsible for the observed antioxidant effect.

Animals↗
PubMed1992

Formation of stable free radicals from kampo medicines TJ-9, TJ-15, TJ-23, TJ-96, TJ-114 and their antioxidant effect on low density lipoproteins.

The Japanese herbal Kampo medicines TJ-9 (A), TJ-15 (B), TJ-23 (C), TJ-114 (D) and TJ-96 (E) were effective (2-5x less than alpha-tocopherol) in inhibiting a copper-induced peroxidation of low density lipoprotein. Kampo medicines dissolved in n-butanol formed stable free radical(s), detected by EPR spectroscopy as a single asymmetric line with g-value g = 2.005. The radical concentration increased in the order: C less than D approximately A approximately E less than B. When the Kampo medicines were oxidized in n-butanol by excess of PbO2 their radical concentration increased 7-15 fold and was in the order C less than D less than A approximately E much less than B. A relationship between the potency of the medicines to inhibit peroxidation of LDL and their ability to form stable free radicals upon oxidation was observed. The medicine which formed more radicals was more efficient in inhibiting peroxidation of LDL. In order to study whether Kampo medicines can reduce alpha-tocopherol radical, the alpha-tocopherol radical was generated by the reaction of alpha-tocopherol with UV irradiated di-tert-butylperoxide and by autooxidation of alpha-tocopherol in n-butanol (25 microliters ml-1) in air. In both systems vitamin-C greater than Kampo B decreased the concentration of the alpha-tocopherol radical and the EPR spectrum of Kampo B stable radical(s) appeared. The effect of other Kampo medicines was not clearly seen since their EPR spectra were superimposed with the spectrum of the alpha-tocopherol radical. The results indicate that Kampo medicines possess electron donor properties and ability to form stable radical(s). The results may contribute to understanding beneficial effects of Kampo medicines in diseases in which free radical damage is suggested.

Antioxidants↗
PubMed1992

[Local anesthetics. CVII. Local anesthetic effects of phenylcarbamates--the effect of connecting chain modification].

The preceding study of the effect of the branching of the connecting chain by the metoxymethyl-, ethoxymethyl- and propoxymethyl group on the alpha carbon on local anaesthetic activity was a stimulus for the preparation of 16 drugs of the group of 1-ethoxyethoxymethyl-2-(1-pyrrolidinyl-), 2-piperidino- and 2-(1-perhydroazepinyl) ethyl esters of o-, m- and p-alkoxyphenylcarbamic acids. The discontinuation of the substituent on the alpha carbon of the connecting chain by another oxygen atom (introduction of an ethoxyethoxymethyl group) has a positive effect on surface and infiltration anaesthesia. Of the prepared agents, 2-piperidino- and 2-(1-perhydroazepinyl-) derivatives with a hexyl or heptyloxy group in the o-position of the benzene ring were most effective; they exceeded the standards cocaine and procaine more than one hundred times. p-Derivatives were least effective; in some cases their indices of effectiveness did not achieve the effectiveness of the standards in both surface and infiltration anaesthesia under study. Acute toxicity of all drugs lies within the range of the toxicities of the standards.

Anesthetics, Local↗
PubMed1992

[The effect of kampo preparations and their effect on peptidase activity in damage caused by free radicals].

The activity of peptidases (trypsin from bovine pancreas and trypsin-like enzymes from the liver rat homogenate) was influenced by five preparation of Kampo medicine, TJ-9 (Sho-Saiko-To), TJ-15 (Oren-Gedoku-To), TJ-23 (Toki-Shakuyaku-San), TJ-96 (Saiboku-To), and TJ-114 (Sairei-To) and studied in relation to their effect on the uptake of free oxygen radicals demonstrated earlier. On the basis of increased activity of trypsin and trypsin-like enzymes and the previously found capability of uptaking free oxygen radicals, the mechanism of action of the Kampo preparations may be assumed to be connected not only with a direct support of enzymes of digestion and increased activity of peptidases, capable of eliminating oxidatively damaged proteins, but with an antioxidative effect as well, which prevents increased cumulation of oxidatively damaged macromolecules and the action of superoxide radicals developed earlier by the well-known and trypsin-stimulated conversion of xanthinedehydrogenase to xanthinoxidase.

Animals↗
PubMed1992

[Antioxidative activity of oren-gedoku-to (TJ-15) and toki- shakuyaku-san (TJ-23) in the liver microsomes of rats].

TJ-15 (Oren-Gedoku-To) inhibited enzymatically (NADPH or CumOOH) and non-enzymatically (Fe-askorbate) induced lipid peroxidation in the rat liver microsomes as assessed by the TBA-reactive product accumulation. TJ-23 (Toki-Shakuyaku-San) had little effect on either system. The protective effect of TJ-15 against lipid peroxidation could not be fully accounted for by its action on microsomal electron transfer, as evaluated by studying the kinetics of reduction of cytochrome C. In a free solution TJ-15 and TJ-23 effectively scavenged OH., radicals, as indicated by the inhibition of ethylene production from KMBA, and O2-. anion radicals, as assessed by the inhibitory effect on the rate of NBT reduction. The present results suggest that TJ-15, yet not TJ-23, is capable to reach hydrophobic intra-membrane sites at concentrations at which it is an effective antioxidant. Thus TJ-15 may be a potentially useful protective agent against free radical-mediated damage.

Animals↗
PubMed1992

[Antioxidative properties of the kampo drugs TJ-9, TJ-15, TJ-23, TJ-96 and TJ-114].

Plant extracts from Kampo medicines TJ-9 (A), TJ-15 (B), TJ-23 (C), TJ-114 (D) and TJ-96 (E) inhibited peroxidation of low-density lipoprotein (LDL) in vitro and peroxidation of multilamellar liposomes formed by total lipids isolated fro the rat brain. The order of relative efficacy of the extracts in both experiments was as follows: C < D equal to or greater than A < B. Using EPR spectroscopy, the Kampo extracts were found to be oxidated by means of PbO2 and to become relatively stable radicals, which shows that they possess electro-donor properties. A relationship between their ability to inhibit peroxidation of LDL and liposomes and their ability to become a radical was found. The Kampo medicines which produced more radicals inhibited peroxidation of LDL and liposomes more effectively. By means of EPR spectroscopy, Kampo B was found to reduce the vitamin E radical. The results contribute to the understanding of the positive effects of Kampo extracts in the diseases in which a negative influence of free radicals is assumed.

Animals↗
PubMed1991

Pyridoindole stobadine is a potent scavenger of hydroxyl radicals.

Stobadine is a potent scavenger of OH. radicals generated chemically in a free solution with kappa 2 higher than 10(10).M-1.s-1 as determined by two independent methods, namely destruction of deoxyribose and oxidation of 2-keto-4-methiolbutyric acid (KMBA). The high efficacy of stobadine to prevent ethylene production from KMBA was observed also in enzymatic (xanthine-xanthine oxidase-driven Fenton) and membrane-bound (NADPH-dependent microsomal electron transfer) sources of OH. radicals.

Animals↗
PubMed1991

Processes linked to the formation of reactive oxygen species are not necessarily involved in the development of isoproterenol-induced hypertrophy of the heart. The effect of stobadine.

Administration of stobadine, a cardioprotective substance in investigation prevents a decrease in the content of protein SH groups and glutathione in hearts of rats treated with high doses of isoproterenol (ISO) (30 mg/kg). Moreover, stobadine also attenuated the increase in the content of malondialdehyde and activities of catalase and glutathione reductase as well as a diminution in the GSH/GSSG ratio observed in heart mitochondria isolated from ISO-treated animals. Since stobadine may be considered as a scavenger of reactive oxygen species (ROS), the above effects of the latter substance support the assumption about a possible involvement of reactive oxygen species (ROS) in some processes initiated by administration of ISO in doses inducing cardiac hypertrophy. However our results also indicate that ROS-mediated processes are not necessarily involved in the mechanism of induction of cardiac hypertrophy itself.

Animals↗
PubMed1990

Efficacy of combined ranitidine and pentacaine treatment in experimentally induced gastric damage in rats.

Combined treatment with the H2 antagonist ranitidine and the cytoprotective agent pentacaine was studied in acute gastric lesions induced by phenylbutazone and stress, in chronic gastric ulcers induced by acetic acid, and in Shay's model of gastric secretion stimulated by histamine. In all experimental settings, the effect of the combined treatment was more pronounced than the effect of each drug alone. The resulting antiulcer or antisecretory activity appeared to be additive or, in some cases, synergistic. If confirmed clinically, the combination of ranitidine and pentacaine may prove useful in the treatment of peptic ulcer disease.

Acetates↗
PubMed1990

[The effect of nitrofuran and asymmetrically substituted urea on Trichomonas vaginalis and Tritrichomonas foetus in vitro and in vivo].

Antitrichomonal activity of selected nitrofuran derivatives and asymmetrically substituted ureas was investigated in vitro and in vivo and compared with the activity of the effective therapeutic agent tinidazole. In experimental infection with Trichomonas vaginalis and Tritrichomonas foetus in mice, some substituted urea derivatives exhibited an antiparasitic effect slightly lower than that of tinidazole. The substance N1-(3-nitrophenyl)-N3-(2-pyrimidinyl)urea proved to be the most effective of the substances tested. On the basis of preliminary toxicity tests the chemotherapeutic value of this substance appears to be promising.

Animals↗
PubMed1989

N-oxygenation of stobadine, a gamma-carboline antiarrhythmic and cardioprotective agent: the role of flavin-containing monooxygenase.

1. N-oxygenation of stobadine, a gamma-carboline antiarrhythmic and cardioprotective agent, was investigated in vitro using rat liver preparations. 2. Stobadine N-oxygenase activity was located mainly in the microsomal fraction and exhibited a requirement for oxygen and NADPH. The apparent Km and Vmax values for the process were, respectively, 350 microM and 3.48 nmol/mg protein per min. 3. N-oxygenation of stobadine in rat liver microsomes was not affected by SKF 525-A, carbon monoxide, metyrapone, cyanide or n-octylamine. When guinea-pig liver microsomes were used the reaction was activated by n-octylamine. 4. N-oxygenase activity was strongly inhibited by methimazole and depressed by phenobarbital and 3-methylcholantrene pretreatment. 5. The above results, along with the pH optimum of 8.4, strongly indicate the involvement of flavin-containing monooxygenase in the metabolic N-oxygenation of stobadine. 6. Species difference in liver microsomal N-oxygenase activity was evident, the order of activity being guinea-pig greater than rat greater than rabbit.

Animals↗
PubMed1989

Hydrogen peroxide-dependent liver microsomal N-demethylation and N-oxygenation of stobadine, a gamma-carboline antiarrhythmic and cardioprotective agent.

1. Hydrogen peroxide was capable of supporting the N-methylation and N-oxygenation of stobadine in rat liver microsomes. NADPH and O2 were not required. 2. The metabolic conversions promoted by H2O2 were completely abolished by preheating the microsomes for 5 min at 90 degrees C prior to assay, indicating the enzymic nature of the reaction. 3. The response to phenobarbital pretreatment and to inhibitors such as SKF 525-A, metyrapone and CO indicated participation of cytochrome P-450 in its oxidized form. 4. Microsomal cytochrome P-450 could not be replaced by haemoglobin, catalase, horseradish peroxidase or by its conversion to cytochrome P-420. 5. Comparative experiments on rabbits, guinea pigs and rats showed species differences in the extent of the peroxidatic metabolism of stobadine, the order of activity not being the same for C- and N-oxidation.

Animals↗
PubMed1987

Biotransformation of stobadine, a gamma-carboline antiarrhythmic and cardioprotective agent, in rat liver microsomes.

1. The metabolism of stobadine, a gamma-carboline antiarrhythmic and cardioprotective agent, was investigated in vitro using fortified rat liver microsomal preparations. 2. Two metabolic products, N-desmethyl stobadine and stobadine N-oxide were isolated and identified by means of t.l.c.,g.l.c. -mass spectrometry, n.m.r. spectrometry and comparison with synthetic reference compounds. 3. Stobadine N-oxide was resolved into two optically active stereoisomers which were produced enzymically in approximately equal quantities.

Animals↗