Pituitary Adenylate Cyclase Activating Peptide (1-38) and its analog (Acetyl-[Ala15, Ala20] PACAP 38-polyamide) reverse methacholine airway hyperresponsiveness in rats

The aim of this study was to investigate both functionally and structurally bronchodilator effects of Pituitary adenylate cyclase activating peptide (PACAP38) and acetyl-[Ala15, Ala20] PACAP38-polyamide, a potent PACAP38 analog, in rats challenged by methacholine (MeCh). Male Wistar rats were divided randomly into five groups. Groups 1 and 2 inhaled respectively aerosols of saline or increasing doses of MeCh (0.5, 1, 2.12, 4.25, 8.5, 17, 34 and 68mg/L). The other groups received terbutaline (Terb) (250 µg/rat) (10-6 M), PACAP38 (50 µg/rat) (0.1 mM) or PACAP38 analog (50 µg/rat) associated to MeCh from the dose of 4.25 mg/L. Total lung resistances (RL) were recorded before and 2 min after MeCh administration by pneumomultitest equipment. MeCh administration induced a significant and a dose-dependent increase (p<0.05) of RL compared to control rats. Terb, PACAP38 and PACAP38 analog reversed significantly the MeCh-induced bronchial constriction, smooth muscle (SM) layer thickness and bronchial lumen mucus abundance. PACAP38 analog prevents effectively bronchial smooth muscle layer thickness, mucus hypersecretion and lumen decrease. Therefore, it may constitute a potent therapeutic bronchodilator.

O objetivo deste estudo foi investigar funcionalmente e estruturalmente efeito broncodilatador do peptídeo ativador da adenilato ciclase pituitária (PACAP1-38) e da acetil-[Ala15, Ala20]PACAP 38-poliamida, potente análogo do PACAP-38, nos ratos desafiados pelo metacolina (MeCh). Ratos Wistar machos foram aleatoriamente divididos em cinco grupos. Grupos 1 e 2, inalando aerossóis de solução salina ou doses crescentes de MeCh (0,5, 1, 2,12, 4,25, 8,5, 17, 34 e 68 mg/L). Os outros grupos recebendo terbutalina (Terb) (250 µg/rato) (10-6M), PACAP-38 (50 µg/rato) (0.1 mM) ou análogo do PACAP-38 (50 µg/rato) associados a MeCh na dose de 4,25 mg/L. A resistência pulmonar total (RL) foi registrada antes e 2 min após a administração de Mech pelo equipamento pneumomultiteste. A administração MeCh induziu aumento significativo e dose dependente (p<0,05) de RL em comparação com ratos do grupo controle. Terb e PACAP1-38 e análogo do PACAP-38 reverteram, significativamente, a constrição brônquica induzida por Mech, a espessura do músculo liso (SM) e abundância de muco do lume brônquico. O análogo PACAP-38 do mesmo modo que a Terb impediu a responsividade brônquica a MeCh e pode se constituir em um importante regulador no desenvolvimento da doença inflamatório pulmonar. Contudo, o uso do peptídeo nativo para aplicações terapêuticas é limitado por sua baixa estabilidade metabólica. Consequentemente, o análogo metabolicamente estável representa ferramenta promissora no tratamento de doenças pulmonares inflamatórias.

Effects of static magnetic field exposure on hematological and biochemical parameters in rats

The present work was undertaken in order to investigate the effects of static magnetic field (SMF) on growth rates, hematopoiesis, plasmatic proteins levels, glucose concentration, lactate dehydrogenase (LDH) and transaminases activities in male rats. Sub-acute exposure of rats during 5 consecutive days to SMF (1h/day at 128mT) induced an increase of plasma LDH activity (+38 percent, p<0.05), and glucose concentration (+31 percent, p<0.05), whereas haematological parameters, protein levels, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities remained unchanged. SMF exposure of rats during 30 consecutive days (1hour/day at 128mT) decreased significantly growth rates by the second week and increased significantly the plasmatic total protein levels (+62 percent, p<0.05), hemoglobin (+10 percent, p<0.05), red blood cells (+7 percent, p<0.05), white blood cells (+17 percent, p<0.05), and platelet number (+10 percent, p<0.05). Sub-chronic exposure to SMF increased also LDH (+43 percent, p<0.05), AST (+ 41 percent, p<0.05) and ALT activities (+95 percent, p<0.05). In contrast, the glucose concentration was unaffected. These changes suggested that exposure to SMF had a possible effect on the proliferation of blood cells and enzymes release within blood indicating tissue alterations.

Este estudo foi realizado com o obejtivo de investigar os efeitos do campo magnético estático (CMS) nas taxas de crescimento, hematopoiese, concentrações de proteínas plasmáticas, glicemia, da desidrogenase lática (DHL) e transaminases (alanina aminotransferase-ALT e aspartato aminotransferase-AST) em ratos machos. Após exposição de modo sub-agudo durante 5 dias consecutivos ao CMS (1 hora/dia, a 128mT), houve aumento em 38 por cento na concentração de DHL (p<0.05), porém não houve mudanças nos índices hematimétricos, nas proteínas plasmáticas e nas transaminases. Duas semans após exposição ao CMS durante 30 dias consecutivos (CMS (1 hora/dia, a 128mT) houve diminuição significativa das taxas de crescimento e aumento significativo das concetrações de proteínas (+62 por cento, p<0.05), da hemoglobina (+10 por cento, p<0.05), eritrócitos (+7 por cento, p<0.05), leucócitos (+17 por cento, p<0.05) e plaquetas (+10 por cento, p<0.05). A exposição sub-crônica ao CMS induziu aumento da DHL (+43 por cento, p<0.05), AST (+ 41 por cento, p<0.05) e ALT (+95 por cento, p<0.05). Em contraste não houve aumento da glicemia. Estas alterações sugerem que a exposição ao CMS possivelmente influencia a proliferação de células do sistema hematopoiético e a produção enzimática, indicando alterações teciduais.

Antioxidant activity of extract of Rhus oxyacantha root cortex.

In the present study, the root extract of Rhus oxyacantha contained 25.33 mg of catechin equivalent per mg of fresh wt and was found rich in proanthocyanidins compared to vine shoot, grape pips and leaves. The chromatographic analysis of the extract suggested the presence of (+) catechin, (-) epicatechin -3-O-gallate as well as proanthocyanidinic oligomers and polymers. Root cortex inhibited the ascorbic acid oxidation by dioxygen. It also prevented DDT-induced thymocytes death in a dose-dependent manner. The results suggested antioxidant property of root extract of Rhus oxyacantha which could be ascribed to its free radical scavenging nature.

Dieldrin initiates apoptosis in rat thymocytes.

In vitro incubation for 6 hr to pesticide dieldrin resulted in a dose-dependent decrease of cell viability comparable to that of dexamethasone. In vivo experiments also demonstrated that dieldrin administration induced a dose-dependent thymic atrophy which appeared to be mediated by endogenous corticosteroids. Agarose gel electrophorosis analysis, revealed the generation of typical apoptotic oligosomal DNA fragmentation in presence of dieldrin. However, in response to high concentrations of pesticide, cells seemed to undergo necrosis pathway. Thus, it may be concluded that dieldrin induced apoptosis in rat thymocytes.