RESUMEN
Kaliotoxin (KTX), a specific blocker of potassium channels, exerts various toxic effects due to its action on the central nervous system. Its use in experimental model could help the understanding of the cellular and molecular mechanisms involved in the neuropathological processes related to potassium channel dysfunctions. In this study, the ability of KTX to stimulate neuro-immuno-endocrine axis was investigated. As results, the intracerebroventricular injection of KTX leads to severe structural-functional alterations of both hypothalamus and thyroid. These alterations were characterized by a massive release of hormones' markers of thyroid function associated with damaged tissue which was infiltrated by inflammatory cell and an imbalanced redox status. Taken together, these data highlight that KTX is able to modulate the neuro-endocrine response after binding to its targets leading to the hypothalamus and the thyroid stimulation, probably by inflammatory response activation and the installation of oxidative stress in these organs.
Asunto(s)
Eosinófilos/efectos de los fármacos , Hipotálamo/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Venenos de Escorpión/toxicidad , Escorpiones/química , Glándula Tiroides/efectos de los fármacos , Animales , Calcitonina/biosíntesis , Calcitonina/metabolismo , Catalasa/metabolismo , Eosinófilos/inmunología , Glutatión/metabolismo , Hipotálamo/inmunología , Hipotálamo/metabolismo , Inyecciones Intraventriculares , Malondialdehído/metabolismo , Ratones , Infiltración Neutrófila/efectos de los fármacos , Neutrófilos/inmunología , Nitrilos/metabolismo , Oxidación-Reducción , Estrés Oxidativo , Venenos de Escorpión/aislamiento & purificación , Escorpiones/fisiología , Glándula Tiroides/inmunología , Glándula Tiroides/metabolismo , Tirotropina/biosíntesis , Tirotropina/metabolismo , Tiroxina/biosíntesis , Tiroxina/metabolismo , Triyodotironina/biosíntesis , Triyodotironina/metabolismoRESUMEN
SUMMARY: Thyroid C cells hormone, calcitonine, inhibits bone resorption. We have demonstrated that daidzein treatment of orchidectomized rats (model for osteoporosis) stimulated C cells and increased trabecular bone mass. These results suggest that, besides direct action, daidzein may also affect bone structure indirectly through enhancement of thyroid C cell activity. INTRODUCTION: Thyroid C cells produce calcitonin (CT) which acts as an inhibitor of bone resorption. In this study, the influence of daidzein treatment on thyroid C cells, bone structure, and bone function in orchidectomized (Orx) middle-aged rats was investigated. METHODS: Sixteen-month-old Wistar rats were divided into Orx and sham-operated (SO) groups. Half the Orx rats were given subcutaneous injections of daidzein (30 mg/kg b.w./day) for 3 weeks. CT-immunopositive thyroid C cells were morphometrically analyzed. The metaphyseal region of the proximal tibia was measured histomorphometrically, and cancellous bone area (B.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) were calculated. Serum samples were analyzed for CT and osteocalcin (OC), calcium (Ca) and phosphorus concentrations, and urine samples for Ca levels. RESULTS: Treatment of Orx animals with daidzein significantly increased volume of C cells compared to the Orx rats. Daidzein also enhanced B.Ar, Tb.Th, and Tb.N and reduced Tb.Sp. The serum OC and urinary Ca concentrations decreased significantly in comparison with the Orx group. CONCLUSIONS: These findings indicate that daidzein treatment stimulates thyroid C cells, increase trabecular bone mass, and decrease bone turnover in Orx middle-aged rats, which is the model of male osteoporosis.
Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Isoflavonas/farmacología , Osteoporosis/tratamiento farmacológico , Glándula Tiroides/efectos de los fármacos , Animales , Biomarcadores/metabolismo , Conservadores de la Densidad Ósea/uso terapéutico , Calcitonina/biosíntesis , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Isoflavonas/uso terapéutico , Masculino , Orquiectomía , Osteoporosis/patología , Osteoporosis/fisiopatología , Ratas , Ratas Wistar , Glándula Tiroides/metabolismo , Glándula Tiroides/patología , Tibia/efectos de los fármacos , Tibia/patologíaRESUMEN
The absence of serum steroids was demonstrated to restrict proliferation of cultured TT cells (cell line originating from human thyroid medullary carcinoma) and supplementation with calcitriol was found to partially restore the proliferation. Calcitriol stimulated TT cell proliferation by augmenting expression of proliferation-associated proteins and by restricting apoptosis. Moreover, calcitriol decreased the intensity of transcription but failed to change direction of the altemate splicing of the calcitonin gene.