Influência do zinco sobre o efeito do selênio na atividade da enzima δ-ALA-D de fígado, rim e cérebro de camundongos adultos in vitro

Selenium is an essential dietary trace element and its deficiency can cause some pathologies such as cardiac diseases. However, investigations have evidencied the toxicologic effect of organic and inorganic selenium compounds in the organs and enzymes.The present work examined the toxic effect of selenium on δ-ALA-D an enzyme involved in the biosynthesis of tetrapyrrol heme. A possible protective role of zinc on inhibitory effect of selenium was also evaluated. The organic selenium compound, (CH3)2C (Seφ) (0CH3) caused a dose dependent inhibition of renal, hepatic and cerebral δ-ALA-D (p< 0.01). Also was evidencied that the selenium and zinc interaction not was able to restore the δ-ALA-D activity inhibited by selenium but increasing the inhibitory effect from the compound on the renal and cerebral enzyme.O selênio é um elemento traço essencial para o homem e a sua deficiência na dieta está relacionada com o desenvolvimento de uma série de patologias, como as cardiovasculares. No entanto, muitos trabalhos têm evidenciado o efeito tóxico de determinados compostos orgânicos e inorgânicos de selênio em alguns órgãos e enzimas específicas; o qual compromete o funcionamento dos mesmos. Este trabalho aborda especificamente o efeito tóxico do selênio sobre uma das enzimas envolvidas na síntese do heme – a δ-ALA-D – e o possível papel protetor dos íons Zn++ sobre a ação tóxica deste elemento frente a enzima. O composto (CH3)2C (Seφ) (0CH3) nas concentrações testadas (12, 40 e 120 µM), inibi significativamente a atividade da enzima hepática, renal e cerebral (p<0.01). Também foi demonstrado que a interação do (CH3)2C (Seφ) (0CH3) com o ZnCl2 (100Mm) não foi capaz de proteger a enzima da inibição provocada por selênio mas potencializou efeito inibitório do composto na δ-ALA-D renal e cerebral

Tolerância às metilxantinas e interações com o Sistema Dopaminérgico: possíveis implicações clínicas

Recent studies have suggested that methylxanthines could change neuroleptics efficiency, since haloperidol or chlorpromazine-induced catalepsy is reversed by methylxanthines. However, these studies were made with acute administration of the drugs, disregarding the possible development of tolerance to methylxanthines. In the present mini-review of the literature it was observed that few studies investigated the tolerance to methylxanthines, furthermore there is some controversy between them. In our laboratory we found no tolerance to caffeine in relation to the etfect on the rat locomotor activity and its ability in reversing chlorpromazine-induced catalepsy. These results suggest that well-controled clinical studies with psychiatric patients in current use of both kinds of drugs are necessary to establish if methylxanthines actually change neuroleptics antipsychotic efficacy.Trabalhos recentes sugerem que as metilxantinas poderiam interferir com a eficiência terapêutica dos neurolépticos, uma vez que a catalepsia induzida por haloperidol ou clorpromazina é revertida por metilxantinas. Todavia, estes trabalhos forem feitos através da administração aguda das drogas, o que exclui o possivel desenvolvimento de tolerância as metilxantinas. No presente trabalho fez-se uma revisão da literatura e observou-se que os estudos sobre o desenvolvimento de tolerância ás metilxantinas são poucos e, em alguns casos, controversos. Além disto, em nosso laboratório não encontramos tolerância á cafeína no tocante á estimulação da atividade locomotora e á reversão de catalepsia induzida por clorpromazina. Estes resultados demonstram a necessidade da execução de estudos clínicos bem controlados com pacientes psiquiátricos que usem drogas de ambos os grupos para determinar se as metilxantinas interferem efetivamente com a eficácia antipsicótica dos neurolépticos

Differential genotoxicity of diphenyl diselenide (PhSe)2 and diphenyl ditelluride (PhTe)2

Organoselenium compounds have been pointed out as therapeutic agents. In contrast, the potential therapeutic aspects of tellurides have not yet been demonstrated. The present study evaluated the comparative toxicological effects of diphenyl diselenide (PhSe)2 and diphenyl ditelluride (PhTe)2 in mice after in vivo administration. Genotoxicity (as determined by comet assay) and mutagenicicity were used as end-points of toxicity. Subcutaneous administration of high doses of (PhSe)2 or (PhTe)2 (500 µmol/kg) caused distinct genotoxicity in mice. (PhSe)2 significantly decreased the DNA damage index after 48 and 96 h of its injection (p < 0.05). In contrast, (PhTe) caused a significant increase in DNA damage (p < 0.05) after 48 and 96 h of intoxication. (PhSe)2 did not cause mutagenicity but (PhTe)2 increased the micronuclei frequency, indicating its mutagenic potential. The present study demonstrated that acute in vivo exposure to ditelluride caused genotoxicity in mice, which may be associated with pro-oxidant effects of diphenyl ditelluride. In addition, the use of this compound and possibly other related tellurides must be carefully controlled

Estudo da formação de aderências e da cicatrização de anastomoses colônicas em ratos com sepse peritoneal induzida

OBJETIVO: Avaliar os efeitos da sepse abdominal sobre a formação de aderências e a cicatrização de anastomoses colônicas em ratos. MÉTODOS: 40 ratos distribuídos em dois grupos contendo 20 animais, para anastomose do cólon esquerdo na presença (grupo S) ou ausência (grupo N) de indução de sepse por ligadura e punção do ceco (CLP). Cada grupo foi dividido em subgrupos para eutanásia no terceiro (N3 e S3) ou sétimo (N7 e S7) dia de pós-operatório (DPO). Foi avaliada a quantidade de aderências e removido um segmento colônico contendo a anastomose para análise histopatológica, força de ruptura, hidroxiprolina e conteúdo de colágeno tecidual. RESULTADOS: Os animais submetidos à CLP apresentaram maior quantidade de aderências intra-abdominais tanto no 3° DPO (p=0,00) quanto no 7° DPO (p=0,00). Tiveram menores valores de força de ruptura no 3° DPO (p=0,00), porém maiores valores no 7° DPO (p=0,00). Não houve diferença na variação da concentração de hidroxiprolina, conteúdo de colágeno e histopatologia. CONCLUSÕES: A infecção peritoneal desencadeada por CLP aumentou a quantidade de aderências intra-cavitárias. Houve diminuição da resistência de anastomoses cólicas no 3° DPO, com posterior aumento no 7° DPO, sem efeito sobre os outros parâmetros da cicatrização. ________________________________________________________________________________ ABSTRACTPURPOSE: To evaluate the effects of abdominal sepsis on adhesion formation and colon anastomosis healing in rats. METHODS: Forty rats were distributed in two groups containing 20 rats each for left colon anastomosis in the presence (Group S) or absence (Group N) of induced sepsis by cecal ligation and puncture. Each group was divided into subgroups for euthanasia on the third (N3 and S3) or seventh (N7 or S7) post-operative day. The amount of adhesions was evaluated and a segment of the colon was removed for histopathologic analysis, bursting strength assessment, hydroxyproline and the determination of tissue collagen. RESULTS: The subjects which underwent cecal ligation and puncture presented a higher amount of intra-abdominal adherences in both third (p=0,00) and seventh (p=0,00) post-operatory days. Smaller bursting strengths were found in the S3 subgroup, and greater bursting strengths were found in the S7 subgroup. There was no difference in the variations on the concentrations of hydroxyproline, tissue collagen and histopathology. CONCLUSIONS: The peritoneal infection which was developed by cecal ligation and puncture raised the amount of intra-cavitary adhesions. There was a decrease in the amount of colonic anastomosis on the third post-operatory day with a following raise on the seventh without any effects on other healing parameters

Effect of Uncaria tomentosa

Background/Aim. The use of herbal products as a supplement to minimize the effects of chemotherapy for cancer treatment requires further attention with respect to the activity and toxicity of chemotherapy. Uncaria tomentosa extract, which contains oxindole alkaloids, is one of these herbal products. The objective of this study was to evaluate whether Uncaria tomentosa extract modulates apoptosis induced by chemotherapy exposure. Materials and Methods. Colorectal adenocarcinoma cells (HT29 cells) were grown in the presence of oxaliplatin and/or Uncaria tomentosa extract. Results. The hydroalcoholic extract of Uncaria tomentosa enhanced chemotherapy-induced apoptosis, with an increase in the percentage of Annexin positive cells, an increase in caspase activities, and an increase of DNA fragments in culture of the neoplastic cells. Moreover, antioxidant activity may be related to apoptosis. Conclusion. Uncaria tomentosa extract has a role for cancer patients as a complementary therapy. Further studies evaluating these beneficial effects with other chemotherapy drugs are recommended