RESUMO
Expression of proapoptotic Bad and antiapoptotic Bcl-2 proteins in ovarian follicular apparatus of Wistar rats was evaluated on days 3, 7, and 14 after single experimental hyperthermia (EH) followed by therapeutic correction with subcutaneous melatonin (0.1 mg) dissolved in 0.2 ml physiological saline (PS) injected daily for 3 days. Duration of EH was less than 17 min; it was terminated when the rectal temperature attained 43.5°C. In acute posthyperthermia period (on experimental day 3), Bcl-2 and Bad expression area in folliculocytes of the experimental (EH+melatonin) and reference rats simultaneously increased in comparison with the corresponding values in control rats. At this, Bcl-2/Bad ratio of expression areas in experimental and reference rats did not differ from the control level. During the recovery period (on posthyperthermia day 7), Bad protein expression area significantly decreased in experimental rats resulting in elevation of Bcl-2/Bad ratio in comparison with control and reference groups on days 3 and 7. On day 14, Bcl-2 and Bad expression areas and Bcl-2/Bad ratio restored in experimental animals to the corresponding values assessed in control and reference groups. Thus, melatonin produced no effect on Bcl-2/Bad protein expression ratio during acute posthyperthermia period, but reduced the expression area of proapoptotic Bad protein and increased Bcl-2/Bad ratio on posthyperthermia day 7. Thus, melatonin can inhibit apoptosis via mitochondrial pathway in ovarian follicles on posthyperthermia day 7.
Assuntos
Melatonina/farmacologia , Folículo Ovariano/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/metabolismo , Animais , Apoptose/efeitos dos fármacos , Feminino , Hipertermia Induzida , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Folículo Ovariano/efeitos dos fármacos , Ratos Wistar , TemperaturaRESUMO
The expression of apoptosis regulators (proapoptotic protein Bad and anti-apoptotic protein Bcl-2) was analyzed and Bcl-2/Bad ratio in the follicular apparatus of the rat ovary was determined on day 3 after hyperthermia (rectal temperature 43.5°C). Hyperthermia in the catabolic phase leads to different degrees of activation of the molecular "switches" of apoptosis in cells of ovarian follicular epithelium. This was seen from increased intensity of immunohistochemical staining for Bad protein against the background of more pronounced expression of Bcl-2 protein. On day 3 after exposure to hyperthermia, Bcl-2/Bad ratio increased, which reflects antiapoptotic protection of cells and conditions for blockade of mitochondrial pathway of apoptosis in the follicular apparatus of the ovaries during the acute period after hyperthermia.
Assuntos
Hipertermia Induzida/métodos , Folículo Ovariano/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genética , Proteína de Morte Celular Associada a bcl/genética , Animais , Apoptose/genética , Diestro/fisiologia , Feminino , Regulação da Expressão Gênica , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Folículo Ovariano/citologia , Proteínas Proto-Oncogênicas c-bcl-2/agonistas , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais , Proteína X Associada a bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/agonistas , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
We studied the effects of a melatonin-aluminum oxide-polymethylsiloxane complex (complex M) on the expression of apoptosis regulators Bcl-2 and Bad in the liver of homozygous db/db BKS.Cg-Dock7m+/+Leprdb/J mice with obesity and type 2 diabetes. Complex M or placebo was administered daily through the gastric tube during weeks 8-16 of life. In mice with type 2 diabetes mellitus receiving placebo, enhanced immunohistochemical reactions for proapoptotic Bad protein and weak response for anti-apoptotic Bcl-2 protein were observed. Administration of complex M shifted the ratio of apoptosis regulators: the area of Bcl-2 expression significantly increased and against the background of reduced Bad expression area. These findings attest to antiapoptotic effect of complex M in the liver on the model of type 2 diabetes mellitus.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Melatonina/farmacologia , Obesidade/tratamento farmacológico , Substâncias Protetoras/farmacologia , Óxido de Alumínio/química , Animais , Apoptose/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Hepatócitos/metabolismo , Hepatócitos/patologia , Homozigoto , Fígado/metabolismo , Fígado/patologia , Melatonina/química , Camundongos , Camundongos Transgênicos , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Substâncias Protetoras/química , Proteínas Proto-Oncogênicas c-bcl-2/agonistas , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Silicones/química , Proteína de Morte Celular Associada a bcl/antagonistas & inibidores , Proteína de Morte Celular Associada a bcl/genética , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
The effects of melatonin, aluminum oxide, and polymethylsiloxane complex on the expression of LYVE-1 (lymphatic vessel endothelial hyaluronan receptor) in the liver were studied in db/db mice with experimental obesity and type 2 diabetes mellitus. The complex or placebo was administered daily by gavage from week 8 to week 16 of life. The animals receiving the complex exhibited enhanced, in comparison with the placebo group, immunohistochemical LYVE-1+ staining of endothelial cells in sinusoids. Enhanced expression of LYVE-1 was associated with less pronounced dilatation of interlobular arteries, veins, and lymphatic vessels. Thee findings suggest a protective effect of the complex towards structural changes in the liver of mice with obesity and type 2 diabetes.
Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glicoproteínas/agonistas , Hiperglicemia/tratamento farmacológico , Melatonina/farmacologia , Obesidade/tratamento farmacológico , Óxido de Alumínio/química , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Expressão Gênica/efeitos dos fármacos , Glicoproteínas/genética , Glicoproteínas/metabolismo , Artéria Hepática/efeitos dos fármacos , Artéria Hepática/metabolismo , Artéria Hepática/patologia , Homozigoto , Hiperglicemia/genética , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Vasos Linfáticos/efeitos dos fármacos , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Proteínas de Membrana Transportadoras , Camundongos , Camundongos Transgênicos , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Receptores para Leptina/deficiência , Receptores para Leptina/genética , Silicones/químicaRESUMO
The study was conducted on 155 female Wistar rats (aged 3 months, body mass--180-200 g), in diestrus phase of the sexual cycle. The effect of the pineal hormone melatonin (MT) on morphological organization of the follicular apparatus and the vasculature of the ovaries was studied in rats after overheating achieving a rectal temperature of 43.5 degrees C. It was found that hyperthermic exposure lead to an increase of the relative areas of the arteries, veins and lymph vessels of the ovaries. Overheating caused disturbances of folliculogenesis. The injection of MT after exposure to hyperthermia resulted in a quick (already on Day 7 after exposure) recovery of the disturbances of the venous circulation and lymphatic drainage of the ovary, as evidenced by the normalization of the relative sizes of arteries, veins and lymphatic vessels of the ovary, reaching control values. This, in turn, contributed to the reduction of morphological disorders of folliculogenesis and created the conditions for accelerated recovery of the relative area of generative elements of the ovary (at the stages of primary, preovulatory and atretic follicles) as early as 7 days after hyperthermia.
Assuntos
Ciclo Estral , Hipertermia Induzida , Melatonina/farmacologia , Folículo Ovariano/irrigação sanguínea , Animais , Feminino , RatosRESUMO
We studied the effects of melatonin on the status of immune organs and parameters of lipid metabolism in rats with alimentary obesity and parameters of lipid metabolism and immune status in Wistar rats kept on high-fat diet and receiving melatonin solution per os. Melatonin leveled the changes in blood and liver parameters of lipid metabolism, which was paralleled by normalization of cellular composition of immune organs. We conclude that melatonin can be a promising agent for the treatment of lipid metabolism and immune status disorders in alimentary obesity.
Assuntos
Fatores Imunológicos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Melatonina/farmacologia , Obesidade/imunologia , Baço/efeitos dos fármacos , Animais , Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Feminino , Contagem de Leucócitos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Linfócitos/efeitos dos fármacos , Obesidade/sangue , Obesidade/etiologia , Ratos Wistar , Baço/patologia , Triglicerídeos/sangueRESUMO
Whole-body controlled hyperthermia (up to 43.5 degrees C) of Wistar rats with Walker-256 carcinosarcoma was followed by symptoms of enhanced lipid peroxidation for 3-14 days and release of lysosomal enzymes into blood on day 14. Our data, in totality, point to a potential to stimulate tumor cell apoptosis.