Metallothionein 3 attenuated the apoptosis of neurons in the CA1 region of the hippocampus in the senescence-accelerated mouse/PRONE8 (SAMP8) / Metalotioneina 3 atenuou a apoptose dos neurônios da região CA1 do hipocampo em camundongos PRONE8 com envelhecimento acelerado (SAMP8)

OBJECTIVE: Metallothionein 3 (MT-3) has been shown to protect against apoptotic neuronal death in the brains of patients with Alzheimer's disease. Zinc is a potent inhibitor of caspase-3 and its deficiency was found to promote apoptosis. Here, we measured the zinc and copper content in the brains of senescence-accelerated mouse/PRONE8 (SAMP8) and sought to investigate the effect of MT-3 on the apoptosis of neurons in the hippocampal CA1 region of these mice. METHOD: The zinc and copper content in the brain samples of SAMP8 and normal control SAMR1 mice were determined using an atomic absorption spectrophotometer. The mice were administered intraperitoneally for four weeks with MT-3 or MT1 and thereafter apoptosis was measured using the TUNEL method and the expression of anti-apoptotic protein Bcl-2 and proapoptotic protein Bax was examined by immunohistochemistry. RESULTS: Compared with that in SMAR1 mice, the content of zinc in the brains of SAMP8 mice was significantly reduced (P<0.05). Moreover, significant levels of apoptosis of neurons were observed in the hippocampus of SAMP8 mice, which, compared with those in SMAR1 mice, also showed significantly lower levels of Bcl-2 and higher levels of Bax (P<0.05). MT-3 increased zinc concentration in the hippocampus of SAMP8 mice and also significantly decreased apoptosis in these neurons dose-dependently and increased the levels of Bcl-2 and decreased the levels of Bax. CONCLUSION: MT-3 could attenuate apoptotic neuron death in the hippocampus of SAMP8, suggesting that the protein may lessen the development of neurodegeneration.

OBJETIVO: Metalotioneína 3 (MT-3) tem mostrado proteção contra a apoptose neuronal em cérebros de pacientes com doença de Alzheimer. Zinco é um potente inibidor da caspase-3, e sua deficiência pode promover a apoptose. No presente trabalho, foram dosados os níveis de zinco e cobre nos cérebros de camundongos PRONE8 com envelhecimento acelerado (SAMP8), visando investigar o efeito da MT-3 na apoptse dos neurônios da região hipocampal CA1 destes camundongos. MÉTODO: Os níveis de zinco e cobre em amostras cerebrais de camundongos SAMP8 e de controles normais SAMR1 foram determinados por absorção atômica em espectrofotometria. Foram administradas MT-3 ou MT-1 intraperitoneais durante quatro semanas, sendo em seguida avaliada a apoptose pelo método TUNEL , enquanto a expressão da proteína anti-apoptótica Bcl-2 e a proteína pró-apoptótica Bax foram avaliadas por imunohistoquímica. RESULTADOS: Em comparação aos camundongos SMAR1, o nível de zinco nas amostras cerebrais dos camundongos SAMP8 estava significativamente diminuído (P<0.05). Além disto, níveis significativos de apoptose foram observados no hipocampo dos camundongos SAMP8, o que, em comparação com os níveis em camundongos SMAR1, também mostrava níveis significativamente mais baixos de Bcl-2 e níveis mais altos de Bax (P<0.05). MT-3 aumentou a concentração de zinco no hipocampo dos camundongos SAMP8, além de diminuir significativamente a apoptose destes neurônios, de uma forma dose-dependente, ao mesmo tempo que aumentou níveis de Bcl-2 e diminuiu níveis de Bax. CONCLUSÃO: MT-3 pode atenuar a morte neuronal apoptótica no hipocampo de SAMP8, o que sugere que esta proteína possa diminuir a neurodegeneração.

Effects of metallothionein on isolated rat heart / 华中科技大学学报（医学）（英德文版）

To investigate the effects of metallothionein (MT) on isolated rat heart, 16 Wistar rats were randomly divided into 2 groups. In control group (group C), distilled water was injected intraperitoneally and 24 h later isolated hearts were perfused with Langendorff and stored at 4 degrees C for 3 h with histidine-tryptophan-ketoglutarate (HTK) solutions, and then isolated hearts were perfused for 2 h by Langendorff. In experimental group (group E), 3.6% ZnSO(4) was injected intraperitoneally, 24 h later isolated hearts were perfused by Langendorff and stored at 4 degrees C for 3 h with HTK solutions, and then the isolated hearts were perfused for 2 h with Langendorff. MT content, the recovery of hemodynamics, myocardial water content (MWC), lactate dehydrogenase (LDH) and creatine kinase (CK) leakage, adenosine triphosphate (ATP) and malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, myocardial cell Ca(2+) content, Ca(2+)-ATPase activity of mitochondria ([Ca(2+)-ATPase](m)) and its Ca(2+) content ([Ca(2+)](m)), synthesizing ATP activity of mitochondria ([ATP](m)), and the ultrastructure of cells were examined. There were a significant increase in group E in hemodynamic recovery, ATP content, SOD activity, [Ca(2+)-ATPase](m) activity, [ATP](m) activity, and substantial reduction in MWC, LDH and CK leakage, MDA content, myocardial cell Ca(2+) content, [Ca(2+)](m) content, and the ultrastructural injury were obviously milder than that of group C. This study demonstrated that MT has protective effects on isolated rat heart.

Efecto tóxico del ión cadmio sobre la glándula submandibular de rata adulta / Toxic effect of cadmium ion on the adult rat submandibular gland

El estudio tuvo por objetivo investigar histométricamente los efectos tóxicos de la exposición al ión cadmio sobre la glándula submandibular en rata adulta. Ratas machos, de peso aproximado a 170 g recibieron, en el bebedero, una solución de 300 mg de cloruro de Cd/l de agua, durante 6 meses. Otro grupo de animales, después del tratamiento, permaneció en recuperación durante un período adicional de 6 meses. El parénquina de las glándulas submandibulares mostró marcada diferencia entre los animales tratados y controles. Los acinos de las glándulas de las ratas intoxicadas con Cd, eran menores, de forma irregular y con células degeneradas. Los núcleos variaron de tamaño pero no de forma. Los ductos estriados, granuloso y excretores estaban desorganizados, mostrando núcleos menores. El cuadro histológico de la glándula submandibular de las ratas sometidas, a recuperación de la intoxicación, durante 6 meses fue semejante al de los controles. Este resultado fue confirmado mediante el estudio histométrico. Basados en la literatura, los autores afirman que la metalotioneína actúa como agente desintoxicante uniéndose al Cd y que la disminución de su síntesis aumenta la concentración de Cd libre, provocando daños al ADN e inhibiendo la síntesis proteica, como fue observado en el presente trabajo

Metallothionein or metallothionein like proteins and heavy metal toxicity in Oreochromis mossambicus (Peters).

Metallothioneins or metallothionein like proteins protect the biological system by encountering the influx of metal ions. These proteins are present in the contaminated as well as uncontaminated organisms. Studies show that the native metallothioneins or metallothionein like proteins of O. mossambicus is predominantly zinc bound. Increased influx of zinc causes a redistribution of this essential metal to other proteins requiring zinc as co-factor. Influx of mercury is encountered by the displacement of zinc bound to the protein and also by de novo of synthesis of metal binding proteins and subsequent binding of the incoming mercury. Data available show that "spill over" hypothesis is too simple to explain the mechanism of heavy metal toxicity.