RESUMO
Functions of the vitamin D-dependent endocrine system were studied in rats deprived of the vitamin after administration of T-2 toxin. Impairments of calcium metabolism, alterations in the enzymatic activity related to vitamin D3 bioactivation and receptor binding of the hormonal form 1,25(OH)2D3 were similar both in rats deprived of vitamin D, treated with T-2 toxin within 5 days at a dose of 0.54 mg/kg and in the corresponding controls. At the same time, reduction of the calcium metabolism patterns was retarded in rats obtaining vitamin D3 simultaneously with T-2 toxin. This effect was expressed as a decrease in normalization of 25-OHD concentration in blood, absence of renal I-hydroxylase 25-OHD3 activation, inspite of the higher content of parath hormone in blood and of cAMP in kidney, while concentration of bound 1,25(OH)2D3 receptors was distinctly decreased in tissues-targets in vivo. Thus, the effects of T-2 toxin on the vitamin D-dependent endocrine system were manifested as development of the vitamin, secondary deficiency, as resistance of I-hydroxylase 25OHD3 to regulating effect of parath hormone as well as inhibition of interaction between the complexes 1,25(OH)2D3-receptor and chromatin.
Assuntos
Cálcio/metabolismo , Glândulas Endócrinas/fisiopatologia , Toxina T-2/toxicidade , Deficiência de Vitamina D/metabolismo , Animais , Osso e Ossos/metabolismo , Masculino , Ratos , Ratos Endogâmicos , Vitamina D/administração & dosagem , Deficiência de Vitamina D/fisiopatologiaRESUMO
Effects of aflatoxin B1 and T-2 toxin, administered daily within 7 days at the doses of 0.7 mg/kg and 0.54 mg/kg, respectively, on metabolism of Ca and on the vitamin D hormonal system were studied in young rats kept on a ration containing normal (0.025 mg/kg) and high (0.25 mg/kg) amounts of vitamin D. Administration of the mycotoxins caused hypocalcemia, a decrease in absorption of Ca as well as in activity of alkaline phosphatase in small intestine mucose, while alterations in spongy bones (of the type of osteopetrosis) were most distinct in T-2 toxin treatment. Concentration of 25(OH)D3 in blood serum and activity of 25-hydroxylase D3 in liver tissue were decreased by 28% and 58%, respectively, after administration of T-2 toxin, and by 34% nd 33%, respectively, after treatment with aflatoxin B1. In kidney activity of I-hydroxylase 25(OH)D3 was unaltered and the activity of 24-hydroxylase tended to decrease. After treatment with the mycotoxins content of nuclear receptors of 1,25(OH)2D3 was decreased in small intestine mucose, whereas cytoplasmic receptors were increased 2.5-fold, thus indicating the distinct decrease in the receptors internalization. High doses of vitamin D caused an increase of Ca content in blood serum and of its absorption in small intestine as well as normalized Ca content in cortical bone of rats treated with T-2 toxin. At the same time, activity of 1-hydroxylase 26(OH)D3 was increased in liver tissue, while concentration of 1,25(OH)2D3 receptors was reduced in small intestine, but internalization of the hormone receptors was maintained at low level.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Aflatoxinas/toxicidade , Calcitriol/metabolismo , Colecalciferol/metabolismo , Receptores de Esteroides/metabolismo , Sesquiterpenos/toxicidade , Toxina T-2/toxicidade , Aflatoxina B1 , Fosfatase Alcalina/metabolismo , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Osso e Ossos/metabolismo , Calcitriol/sangue , Cálcio/metabolismo , Colecalciferol/sangue , Cromatografia Líquida de Alta Pressão , Mucosa Intestinal/enzimologia , Cinética , Masculino , Ratos , Ratos Endogâmicos , Receptores de Calcitriol , Receptores de Esteroides/efeitos dos fármacosRESUMO
Metabolism of calcium and vitamin D was studied in young rats administered with trichothecene-related mycotoxin deoxynivalenol (vomitoxin) at a daily dose of 10 mg/kg perorally within 7 days. The vomitoxin treatment caused a moderate hypocalcemia, a decreased absorption of calcium in small intestine as well as led to decrease of alkaline phosphatase activity in blood and small intestine mucosal membrane. Density and saturation of bone tissue with minerals were not altered. Concentration of 25-OHD in blood and activity of vitamin D3(25)-hydroxylase in liver tissue were decreased by 40% and 30%, respectively. Development of 1,25(OH)2D3 and 24,25(OH)2D3 as well as concentration of total and free 1,25(OH)2D3 receptors were not altered in kidney. At the same time, these impairments of calcium and vitamin D metabolism were prevented by providing high content of vitamin D in the ration--0.25 mg/kg of food. Impairments in calcium metabolism caused by vomitoxin may be partially related to development of a secondary deficiency in vitamin D.
Assuntos
Cálcio/metabolismo , Colecalciferol/metabolismo , Sistema Enzimático do Citocromo P-450 , Receptores de Esteroides/metabolismo , Tricotecenos/toxicidade , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Calcifediol/sangue , Calcifediol/metabolismo , Calcitriol/sangue , Calcitriol/metabolismo , Cálcio/sangue , Colecalciferol/administração & dosagem , Intestino Delgado/enzimologia , Intestino Delgado/metabolismo , Rim/enzimologia , Rim/metabolismo , Dose Letal Mediana , Fígado/enzimologia , Fígado/metabolismo , Masculino , Ratos , Ratos Endogâmicos , Receptores de Calcitriol , Receptores de Esteroides/efeitos dos fármacos , Esteroide Hidroxilases/metabolismo , Vitamina D3 24-HidroxilaseRESUMO
Experimental rats received T-2 toxin (0.063 mg/kg), deoxynivalenol (1.6 mg/kg) and aflatoxin B1 (0.008 mg/kg) during 6 months. Moderately manifest changes were detected in metabolic enzyme activity of foreign substances in the liver and small intestine mucosa. All mycotoxins induced weak hypocalcemia, while ionized calcium concentration in the blood serum decreased only after T-2 toxin administration that was attended by an increase of PTH level. Alkaline phosphatase activity and calcium transport in the small intestine were not significantly changed. Concentration of 25-OHD in the blood serum and 25-hydroxylase D3 activity in the liver decreased in rats given T-2 toxin. Formation of 1,25(OH)2D3 and 24,25(OH)2D3 in the kidneys was not significantly changed, while T-2 toxin inhibited regulatory changes in 1-hydroxylase 25-OHD3 activity in response to the action of PTH and adenylate cyclase activator forskolin. The results of the investigation have evidenced that calcium metabolism disorders during chronic action of mycotoxins could be partially associated with secondary vitamin D deficiency.