RESUMO
The effects of TLR4 blocker on blood cell morphology, concentrations proinflammatory cytokines, and functional state of the liver and kidneys were studied in outbred male rats (n=60) after intravenous injection of 20 mg/kg LPS isolated from opportunistic Proteus mirabilis strain ATCC 51393. TLR4 blocker TLR4-IN-C34 was injected intravenously in a dose of 1 mg/kg/day over 3 days. Systemic inflammatory reaction induced by LPS was characterized by elevation of serum TNFα, IL-1ß, IL-6, erythrocyte sedimentation rate, leukocytosis, and thrombocytosis. Increased activity of hepatocyte enzymes (ALT, alkaline phosphatase, and lactate dehydrogenase), retention of nitrogen metabolites (urea and creatinine), elevated content of protein oxidation products, and enhanced protein catabolism were also observed. Administration of TLR4 blocker reduced parameters of inflammatory reaction and prevented the development of hypercatabolic syndrome; endotoxicosis and kidney function indicators approached the normal levels.
Assuntos
Anti-Inflamatórios/farmacologia , Leucocitose/tratamento farmacológico , Lipopolissacarídeos/antagonistas & inibidores , Piranos/farmacologia , Sepse/tratamento farmacológico , Trombocitose/tratamento farmacológico , Receptor 4 Toll-Like/antagonistas & inibidores , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Animais não Endogâmicos , Creatinina/sangue , Modelos Animais de Doenças , Regulação da Expressão Gênica , Injeções Intravenosas , Interleucina-1beta/sangue , Interleucina-1beta/genética , Interleucina-6/sangue , Interleucina-6/genética , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , L-Lactato Desidrogenase/sangue , Leucocitose/sangue , Leucocitose/patologia , Lipopolissacarídeos/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Proteus mirabilis/química , Ratos , Sepse/sangue , Sepse/patologia , Transdução de Sinais , Trombocitose/sangue , Trombocitose/patologia , Receptor 4 Toll-Like/sangue , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Ureia/sangueRESUMO
Optimal combination of chlorhexidine bigluconate with ascorbic acid, succinic acid, and zinc oxide was found as a result of comparative trials. The composition shows antioxidative effects and is capable of initiating antibody producing and phagocytosis. This combination can be used as an active substance of orodispersible tablets for the treatment respiratory tract infections.
Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Clorexidina/análogos & derivados , Exsudatos e Transudatos/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Ácido Succínico/farmacologia , Óxido de Zinco/farmacologia , Administração Oral , Animais , Antibacterianos/uso terapêutico , Formação de Anticorpos , Antioxidantes/uso terapêutico , Ácido Ascórbico/química , Ácido Ascórbico/uso terapêutico , Clorexidina/química , Clorexidina/farmacologia , Clorexidina/uso terapêutico , Combinação de Medicamentos , Escherichia coli/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fagocitose/efeitos dos fármacos , Ratos , Staphylococcus aureus/efeitos dos fármacos , Ácido Succínico/química , Ácido Succínico/uso terapêutico , Comprimidos , Óxido de Zinco/química , Óxido de Zinco/uso terapêuticoRESUMO
Preclinical safety of reamberin, a preparation of succinic acid intended for the treatment of patients with shock conditions of different etiology, and remaxol a drug intended for the treatment of patients with liver dysfunction caused by acute intoxication was performed. Both medicines belong to the 5th class of practically non-toxic drugs. Their administration to experimental animals for 30 days did not cause toxic effects on the functional and morphological state of main systems and organs. Both medicines do not affect specific (humoral and cellular) and non-specific immune response and do not cause sensibilization, mutagenic, embryotoxic and teratogenic effects, and also do no alter parameters of reproductive functions of rats.
