RESUMO
Hepatotoxicity is the most serious adverse effect related to tuberculosis treatment which interrupts the successful completion of tuberculosis treatment. The purpose of this study was to assess therapeutic effect of thymoquinone (TQ) against anti-tuberculosis drugs (ATD) induced liver damage. Rats were treated with ATD for 8 weeks (3 days/week) as given for the treatment of TB. This was followed by therapy of TQ for 8 weeks (3 days/week). Administration of combined ATD induced hepatotoxicity was evident from a significant elevation in the AST, ALT, ALP, bilirubin, albumin, cholesterol, urea, uric acid, creatinine, LPO and decreased activities of enzymes. These altered variables were significantly reversed toward control after treatment with TQ. Histological studies also supported biochemical findings. Results of this study strongly indicated protective effect of TQ and thus, can be expected as promising protective agent in maintenance of normal hepatic function during treatment with ATD.
Assuntos
Antituberculosos/antagonistas & inibidores , Antituberculosos/toxicidade , Benzoquinonas/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Análise de Variância , Animais , Análise Química do Sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Etambutol/antagonistas & inibidores , Etambutol/toxicidade , Feminino , Isoniazida/antagonistas & inibidores , Isoniazida/toxicidade , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/metabolismo , Fígado/patologia , Testes de Função Hepática , Pirazinamida/antagonistas & inibidores , Pirazinamida/toxicidade , Ratos , Ratos Sprague-Dawley , Rifampina/antagonistas & inibidores , Rifampina/toxicidade , Superóxido Dismutase/metabolismoAssuntos
Etambutol/metabolismo , Mycobacterium/metabolismo , Adsorção , Sítios de Ligação , Radioisótopos de Carbono , Etambutol/antagonistas & inibidores , Etambutol/farmacologia , Sulfato de Magnésio/farmacologia , Mycobacterium/efeitos dos fármacos , Mycobacterium/crescimento & desenvolvimento , Cloreto de Sódio/farmacologiaRESUMO
Magnesium sulfate and spermidine were tested for their effects on binding of (14)C-ethambutol by Mycobacterium smegmatis. Concentrations were used that protected the organism from ethambutol inhibition. Sodium salts were examined as possible ethambutol antagonists to test the previously reported specificity of the divalent cation salt effect. Consistent with growth-protection experiments, 20 mM MgSO(4) or 2.0 mM spermidine prevented and reversed (14)C binding by cells shaken with 0.2 mug of (14)C-ethambutol per ml of Sauton medium at 37 C. Sodium salts were not effective ethambutol antagonists when tested at 20 mM, but at concentrations equivalent in ionic strength (mu) to that provided by 20 mM MgSO(4) they were effective. Thus, 20 mM MgSO(4), 80 mM NaCl, or 27 mM Na(2)SO(4) (mu = 0.08) all gave similar results in growth protection and binding experiments, suggesting that MgSO(4) antagonism is a nonspecific ionic effect. Because spermidine (mu
