The intracellular superoxide and glutathione disulphide concentrations increased in Penicillium chrysogeum treated with 50,250 or 500 μM menadione (MQ). A significant increase in the intracellular ...peroxide concentration was also observed when mycelia were exposed to 250 or 500 μM MQ. The specific activity of Cu,Zn and Mn superoxide dismutases, glutathione reductase and glutathione S-transferase as well as the glutathione producing activity increased in the presence of MQ while glutathione peroxidase and γ-glutamyltranspeptidase were only induced by high intracellular peroxide levels. The glucose-6-phosphate dehydrogenase and catalase activities did not respond to the oxidative stress caused by MQ.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Methotrexate (MTX) was investigated for possible effect on the metabolism of ethoxyresorufin, pentoxyresorufin and ethoxycoumarin, the model substrates of cytochrome P450. The investigation was ...carried out in liver microsomes of rats pretreated with classical inducers of cytochrome P450 as well as in microsomes of two human livers. Furthermore, we measured the conversion of MTX (100microM) to its main metabolite, 7-hydroxymethotrexate (7-OHMTX), in microsomes and cytosolic fractions of rat and human livers. The inhibition of 7-OHMTX formation by menadion (inhibitor of aldehyde oxidase) and allopurinol (inhibitor of xanthine oxidase) was studied in the cytosol of rat and human livers. In both species, MTX in the concentration range 0.5-500 microM exerted no inhibitory effect on enzymatic activities associated with cytochrome P450. Moreover, we did not observe any measurable formation of 7-OHMTX in liver microsomes. MTX was metabolized at a similar rate in the cytosol of rat and human liver. Allopurinol (100 microM) reduced the rate of MTX hydroxylation by 31.5% in the cytosol of human livers but had no effect in the rat. Menadion (100 microM) decreased the rate of 7-OHMTX formation in the cytosol of human and rat liver by 69% and 94%, respectively. Our results confirmed that MTX is oxidized by a soluble enzymatic system in both the rat and human liver. In human tissues, both aldehyde oxidase and xanthine oxidase may play an important role in the metabolism of MTX. Depression of cytochrome P450 and related enzymatic activities observed in vivo cannot be explained by a direct inhibitory action of MTX on cytochrome P450.
Effect of animal erythrocytes incubated with glycosaminoglycanes and menadion on the immune response of mice and rats with acute hemorrhage was investigated. The results of the study proves the ...interest in elaboration of the methods to produce erythrocytes stroma incubated extracorporately with menadion and glucosaminoglycanes. This preparation may be useful for immunomodulating effect in the case of acute hemorrhage and also in other stress situations, connected with changes of erythrocytes properties and activity.
Incubation of isolated rat hepatocytes with cytotoxic concentrations of menadione resulted in inhibition of plasma membrane Ca super(2+)-ATPase activity. This could be restored by subsequent ...treatment with either dithiothreitol or reduced glutathione, suggesting that the inhibition by menadione was due to oxidation of sulfhydryl groups critical for Ca super(2+)-ATPase activity.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Methotrexate (MTX) was investigated for possible effect on the metabolism of ethoxyresorufin, pentoxyresorufin and ethjxycoumarin, the model substrates of cytochrome P450. The investigation was ...carried out in liver microsomes of rats pretreated with classical inducers of cytochrome P450 as well as in microsomes of two human livers. Firthermore, we measured the conversion of MTX (100 ^M) to its main metabolite, 7-hydroxymethotrexate (7-OHMTX), in microsomes and cytosolic fractions of rat and human livers. The inhibition of 7-OHMTX formation by menadion (inhibitor of aldehyde oxidase) and allopurinol (inhibitor of xanthine oxidase) was studied in the cytosol of rat and human livers. In both species, MTX in the concentration range 0.5-500 /¿M exerted no inhibitory effect on enzymatic activities associated with cytochrome P450. Moreover, we did not observe any measurable formation of 7-OHMTX in liver microsomes. MTX was metabolized at a similar rate in the cytosol of rat and human liver. Allopurinol (100 /iM) reduced the rate of MTX hydroxylation by 31.5 % in the cytosol of human livers but had no effect in the rat. Menadion (100 y/M) decreased the rate of 7-OHMTX formation in the cytosol of human and rat liver by 69 % and 94 %, respectively. Our results confirmed that MTX is oxidized by a soluble enzymatic system in both the rat and human liver. In human tissues, both aldehyde oxidase and xanthine oxidase may play an important role in the metabolism of MTX. Depression of cytochrome P450 and related enzymatic activities observed in vivo cannot be explained by a direct inhibitory action of MTX on cytochrome P450
Objetivou-se estudar os efeitos da combinação de ácido L-glutâmico (L-Glu) e vitamina K na composição bioquímica de fêmures (proteínas colagenosas; não-colagenosas e totais) de frangos de corte. O ...experimento, que teve 14 dias de duração, foi conduzido em delineamento inteiramente casualizado, em fatorial 2 × 4, com dois níveis de ácido L-glutâmico (6,25 e 12,5%) combinados com quatro níveis de vitamina K (0,02; 0,2; 2,0 e 20,0 mg/kg de ração), cada combinação com quatro repetições de dez animais. Foram utilizados pintos machos, Avian Farm, de 1 dia, criados em baterias aquecidas e alimentados à vontade com dieta básica contendo L-aminoácidos essenciais, minerais e vitaminas (exceto vitamina K) suplementada com ácido L-glutâmico e vitamina K. Ao término do experimento, os animais foram sacrificados por deslocamento cervical e seus fêmures removidos, medidos, desengordurados e pesados. Não foi observada interação significativa entre ácido L-glutâmico e vitamina K para os parâmetros estudados. Os teores de proteínas não-colagenosas foram maiores e o de proteínas colagenosas, menores nos fêmures dos pintos alimentados com a ração com 6,25% de ácido L-glutâmico. Os teores de proteínas totais, no entanto, não foram afetados pelos níveis de ácido L-glutâmico e de vitamina K. Os níveis de vitamina K tiveram efeito quadrático decrescente nos teores de proteínas não-colagenosas e efeito crescente na composição de proteínas colagenosas dos fêmures. A composição em proteínas colagenosas e não-colagenosas pode ser utilizada como indicador bioquímico de anormalidades de pernas causadas por baixo nível de nitrogênio não-específico.
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