RESUMO
Prostatotropic activity of (3,5-dimethyl-4-hydroxy)benzyl thiododecane (T-DD) was evaluated on a model of benign prostatic hyperplasia induced in Wistar rats by chronic (2 months) intraperitoneal administration of sulpiride (40 mg/kg). Morphometric analysis of the dorsolateral lobe of the prostate showed that after the 2-month course of intragastric T-DD (100 mg/kg) administered in parallel with sulpiride, the volume density of glandular epithelium decreased by 1.7 times, while the volume density of prostate stroma increased by 2 times. After administration of the reference drug Permixon at a dose of 50 mg/kg, the volume densities of epithelium decreased by 1.3 times and stromal volume density increased by 1.5 times. The observed effects are presumably related to suppression of 5α-reductase activity and modulation of estrogen receptors in the prostate.
Assuntos
Próstata/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/patologia , Agentes Urológicos/uso terapêutico , Animais , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Ratos , Ratos Wistar , Serenoa , Sulpirida , Agentes Urológicos/químicaRESUMO
The study examined dynamics of the effect of novel phenol antioxidant preparation 3-(3'-tertbutyl- 4'-hydroxyphenyl)propyl thiosulfonate sodium (TS-13) on expression of antioxidant protection enzymes genes GSTP1 and NQO1 and on the content of protein transcription factors NF-κB and ATF-2 in mouse liver. Expression of GSTP1 gene decreased significantly on days 4 and 7 after per os administration of TS-13 (100 mg/kg), but increased on post-administration day 14. On days 7 and 14 post-administration, expression of NQO1 gene was significantly increased. On day 7, the hepatic content of the phosphorylated form of ATF-2 and two subunits of nuclear factor NF-κB (p50, p65) decreased significantly.
Assuntos
Fator 2 Ativador da Transcrição/genética , Antioxidantes/farmacologia , Glutationa S-Transferase pi/genética , NAD(P)H Desidrogenase (Quinona)/genética , NF-kappa B/genética , Ácidos Tiossulfônicos/farmacologia , Fator 2 Ativador da Transcrição/metabolismo , Administração Oral , Animais , Expressão Gênica/efeitos dos fármacos , Glutationa S-Transferase pi/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NAD(P)H Desidrogenase (Quinona)/metabolismo , NF-kappa B/metabolismo , Fosforilação , Fatores de TempoRESUMO
A hepatoprotective effect of thiophan was studied on the model of carbon tetrachloride-induced hepatitis in rats. Therapeutic administration of thiophan repairs the antitoxic function of liver, normalizes cytolysis marker activity, and improves the synthetic function of liver and the carbohydrate and lipid metabolism. The hepatoprotective activity of thiophan is similar to effect of silimarin.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Hepatite Animal/tratamento farmacológico , Fígado/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Tiofenos/uso terapêutico , Alanina Transaminase/análise , Animais , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/análise , Bilirrubina/análise , Metabolismo dos Carboidratos/efeitos dos fármacos , Tetracloreto de Carbono/administração & dosagem , Tetracloreto de Carbono/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Hepatite Animal/induzido quimicamente , Hepatite Animal/metabolismo , Hepatite Animal/patologia , Inativação Metabólica , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Substâncias Protetoras/administração & dosagem , Ratos , Ratos Wistar , Silimarina/administração & dosagem , Silimarina/uso terapêutico , Tiofenos/administração & dosagem , Triglicerídeos/análiseRESUMO
The effect of hydrophilic synthetic antioxidant TC-13 (3-(3'-tert-butyl-4'-hydroxyphenyl)propylthiosulfonate sodium) inducing the antioxidant-responsive element on the lifespan of Drosophila melanogaster was studied. Addition of 1% TC-13 to diets prolonged the lifespan of long-lived D. melanogaster Canton S strain females and males, but not of short-lived Oregon R insects and reduced the mean lifespan of D. melanogaster males of the lgl558OR/Cy strain containing a recessive lethal mutation of tumor suppressor in the heterozygotic state. The geroprotective effects of TC-13 synthetic phenol antioxidant depended on D. melanogaster genotype and gender.
Assuntos
Antioxidantes/farmacologia , Drosophila melanogaster/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Fenol/farmacologia , Animais , Antioxidantes/síntese química , Antioxidantes/química , Drosophila melanogaster/genética , Feminino , Genótipo , Longevidade/genética , Masculino , Estrutura Molecular , Fenol/síntese química , Fenol/química , Fatores SexuaisRESUMO
Carbon tetrachloride-induced hepatitis in rats is accompanied by blood hyperviscosity syndrome development. A course intragastric administration of thiophane under these conditions prevents the increase in whole blood viscosity by normalizing the microrheological indices (deformability and aggregation of erythrocytes), which is manifested by increasing oxygen availability for tissues.
Assuntos
Viscosidade Sanguínea/efeitos dos fármacos , Intoxicação por Tetracloreto de Carbono/sangue , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/sangue , Agregação Eritrocítica/efeitos dos fármacos , Deformação Eritrocítica/efeitos dos fármacos , Tiofenos/farmacologia , Animais , Masculino , Ratos , Ratos WistarRESUMO
Effect of seven structurally similar N, N-dimethyl-(4-hydroxyaryl)alkylammonium chlorides in the presence and in the absence of hydrogen peroxide on the survival of E. coli cells AB1157 and its isogenic strain BH910 defective in genes of repair enzymes has been analyzed. Among the studied compounds only chloride of N,N-dimethyl-(3,5-dimethyl-4-hydroxybenzyl)ammonium (C1) has no cytotoxic properties and increases the survive of the cells of both strains in the presence of H2O2 better than trolox (water soluble analog of alpha-tocopherol). C1 analogs: 3-methyl-(5-di(tert-butyl)-4-hydroxybenzyl) and 3-(3,5-di(tert-butyl)-4-hydroxyphenyl)propyl)amines derivatives effectively protected from H2O2 only mutant cells BH910. Among the structural analogs of C1 cytotoxicity increases at substitution of methyl groups in aromatic cycle by tert-butyl and cyclohexyl groups. Only C1 among the seven new compounds is the most promising antioxidant for the subsequent more detailed analysis.
Assuntos
Aminas/farmacologia , Antioxidantes/farmacologia , Escherichia coli/crescimento & desenvolvimento , Fenóis/farmacologia , Peróxido de Hidrogênio/farmacologia , Oxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
Beginning with the first hours of experiments, cisplatin evoked an increase of chromosomal aberrations in CBA/CaLac bone marrow cells. Significant increase of structural infringements of chromosomes due to chromatid breaks was revealed in metaphase plates of murine bone marrow preparations through 24 h after cisplatin intraperitoneal introduction. In late terms of research (90th day), the high level of aberrations of chromosomes was retained. The most pronounced correction of cisplatin mutagenicity was achieved using a preliminary course of thiophan introduction.
Assuntos
Aberrações Cromossômicas/induzido quimicamente , Aberrações Cromossômicas/efeitos dos fármacos , Cisplatino/efeitos adversos , Tiofenos/farmacologia , Animais , Medula Óssea/patologia , Cisplatino/farmacologia , Masculino , Camundongos , Mutagênicos/efeitos adversos , Mutagênicos/farmacologia , Fatores de TempoRESUMO
Structurally related phenols containing the p-alkylthiosulfonate substituent and partially hindered by tert-butyl groups were synthesized for the search and development of new synthetic antioxidant, which would be effective in vivo in preventing free radical-induced pathological processes. Sodium 3-(3'-tert-butyl-4'-hydroxyphenyl)propylthiosulfonate had high antiinflammatory activity and produced a dose-dependent effect (IC(50)=36 mg/kg). Changes in the length of the carbohydrate chain in the p-alkyl substituent had no effect on in vitro antiradical activity of the test compounds. However, the decrease in the length of this chain by one methylene unit was accompanied by reduction of antiinflammatory activity of the end product. Lengthening of the chain did not modulate these properties.
Assuntos
Anti-Inflamatórios/química , Antioxidantes/química , Antioxidantes/farmacologia , Fenóis/química , Enxofre/química , Animais , Anti-Inflamatórios/síntese química , Antioxidantes/síntese química , Pé/patologia , Fenóis/síntese química , Relação Quantitativa Estrutura-Atividade , Ratos , Ratos WistarRESUMO
The antioxidant activity, mutagenicity, and genotoxicity of bis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propyl)sulfide (thiophane) were studied using bacterial tests. The results of both an Ames test and SOS chromotest, as well as those studying the survival of E. coli cells deficient in enzymes responsible for the repair of DNA oxidative damage, testify to the fact that thiophane is not mutagenic and genotoxic, and it protects Salmonella typhimurium cells better than the well-known antioxidant trolox.
Assuntos
Antioxidantes/farmacologia , Fenóis/farmacologia , Sulfetos/farmacologia , Antioxidantes/toxicidade , Dano ao DNA , Escherichia coli/efeitos dos fármacos , Testes de Mutagenicidade , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Salmonella typhimurium/efeitos dos fármacos , Sulfetos/toxicidadeRESUMO
Three new sulfur-containing derivatives of 2,6-dimethylphenol were synthesized. Their antioxidative activity, mutagenicity, and genotoxicity were examined by bacterial tests and by calculating the dominant lethal mutations in murine embryonic cells. It was shown that all the compounds synthesized have a marked antioxidative effect and no genotoxic or mutagenic properties. One of the antioxidants, 4-(3-dodecylthiopropyl)-2,6-dimethylphenol, increases the survival of cells of both the wild-type Escherichia coli strain and bacterial strains defective in the genes of repair enzymes and has a more distinct antioxidative effect than the classic antioxidants alpha-tocopherol and trolox, increasing the survival of cells devoid of repair enzymes.
Assuntos
Antioxidantes/síntese química , Sulfetos/síntese química , Xilenos/síntese química , Antioxidantes/química , Antioxidantes/farmacologia , Cromanos/farmacologia , Dano ao DNA , DNA Glicosilases/genética , DNA-Formamidopirimidina Glicosilase/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Mutação , Pirofosfatases/genética , Relação Estrutura-Atividade , Sulfetos/química , Sulfetos/farmacologia , Xilenos/química , Xilenos/farmacologia , alfa-Tocoferol/farmacologiaRESUMO
We proposed a combination of methods to study antioxidant properties of compounds, including evaluation of the capacity of the test preparations to inhibit peroxidation of unsaturated lipids (in model systems with oxidation of ethyl oleate; aqueous emulsion medium) and low-density lipoproteins (in the presence of transition metal ions), generation of superoxide anion radical (system of lucigenin, xanthine oxidase, and xanthine) and NO(*)/ONOO(-) (system of SIN-1 and lucigenin), and induction of respiratory burst in blood granulocytes (luminol-induced and lucigenin-induced reaction after zymosan stimulation). In vitro study showed that the antioxidant properties of synthetic water-soluble phenols depend strongly on masking of the phenol OH group and nature of the ionogenic fragment in the p-propyl substituent.
Assuntos
Antioxidantes/metabolismo , Animais , Granulócitos/efeitos dos fármacos , Granulócitos/metabolismo , Lipoproteínas LDL/metabolismo , Substâncias Luminescentes/farmacologia , Luminol/farmacologia , Oxirredução , Ratos , Explosão Respiratória/efeitos dos fármacos , Superóxidos/metabolismo , Xantina/metabolismo , Xantina Oxidase/metabolismo , Zimosan/farmacologiaRESUMO
We synthesized a series of structurally related water-soluble alkyl phenols - sodium 4-hydroxyphenyl propyl sulfonates and thiosulfonates with different number of tert-butyl groups at the ortho-position. In experimental systems of transient metal-induced ethyl oleate and low-density lipoprotein oxidation the antioxidant activity of the compounds increased when the tert-butyl group number at the ortho-position increased and when the sulfonate group was replaced with thiosulfonate. Compounds containing thiosulfonate group in para-propyl substituent also more effectively inhibited reactive oxygen metabolites generated in xanthine-xanthine oxidase system and during morpholinosydnonimine decomposition compared to sulfonate-containing analogs. Phenols with one tert-butyl group at the ortho-position have been shown to exhibit the highest antiinflammatory activity in the model of carrageenan-induced rat paw inflammation, as well as with regard to the expression of the glutathione S-transferase P1-1 gene in HepG2 human hepatoma cell line. Thus, it can be reasonably speculated that the antiinflammatory activity of sulfur-containing phenolic antioxidants in vivo is mediated by their effect on redox-sensitive transcription factors.