Characterization of a refinement of the "pylorus ligation" model of rat gastric ulceration resulting in "no pain" and a more specific pharmacological response.

INTRODUCTION: The pharmacological assessment of the factors for gastric protection of a test substance should involve experimental models that can determine the involvement of cytoprotective factors, as well as their influence on the secretion of hydrochloric acid. The original protocol of pylorus ligation in rats proposed by Shay et al. in 1945, still in use today, provides a latency time of 240 min without considering the effect of postoperative pain in the mechanisms of peptic ulcer. This paper proposes a modification of this experimental protocol by eliminating the pain throughout the postoperative period, as a refinement of the test with consequent improvement of the pharmacological response. METHODS: Adult male Wistar/Uni rats underwent surgical ligation of the pylorus and were kept anesthetized throughout the experimental period (4h) in contrast to the other experimental groups that followed the original protocol proposed by Shay et al., 1945. RESULTS: We were able to determine effective doses for a positive control, as well as of a variety of secretagogues in the new experimental protocol proposed. DISCUSSION: The suppression of post-surgical pain, through the use of anesthesia throughout the experimental period, brought several benefits for the study of gastric acid secretion, rendering a more homogeneous pharmacologic response in non-inbred animals, thus being an effective experimental procedure.

Atividade antiulcerogênica e mecanismo de ação de alimento fermentado à base de trigo e soja utilizado como alimento funcional / Antiulcer activity and mechanism of action of fermented food based on wheat and soy beans used as functional food

Objetivo: estudar o mecanismo de ação e avaliar a proteção da mucosa do estômago de ratos Wistar pela atividade de um alimento com propriedades funcionais à base de trigo e soja fermentado, a fim de reduzir o processo ulcerativo induzido por etanol. Métodos: nesse estudo foram utilizados os modelos de indução de úlcera por etanol absoluto em ratos Wistar tratadospreviamente com Indometacina (5mg/kg de peso), N-etilmaleimida (10mg/kg de peso) e L-NAME (5mg/kg de peso). No mesmo modelo de indução de úlcera foi realizada a administração de solução salina (10mL/kg de peso) como controle negativo, Carbenoxolona (200mg/kg) como controle positivo e o produto fermentado na dose de 2000mg/kg de peso animal. Resultados: na verificação da atividade antiulcerogênica do fermentado em pó, o Índice de Lesões Ulcerativas (ILU) foi inibido em 29,9%, enquanto a Carbenoxolona utilizada como controle positivo foi capaz de inibir o ILU em 83,7%. No modelo de indução de úlcera por etanol absoluto, com a administração prévia de L-NAME, N-etilmaleimida e da Indometacina, constatou-se que, nos dois primeiros tratamentos, o fermentado apresentou atividade antiulcerogênica de 50,9% e 28,3%, respectivamente e no tratamento com Indometacina, o produto não apresentou atividade antiulcerogênica, o que sugere que seu mecanismo de ação ocorre pela síntese ou redução da degradação de prostaglandinas que são uma das responsáveis pela citoproteção gástrica. Conclusão: com base nos dados obtidos nesse experimento com ratos para avaliação da atividade antiulcerogênica e mecanismo de ação do produto fermentado, concluiu-se que este provavelmente promove a citoproteção gástrica especialmente através dos níveis de prostaglandinas.

Objective: to study the mechanism of action and evaluate the protection of the stomach mucosa of Wistar rats due to the activity of a fermented soy and wheat-based food product with functional properties in order to reduce the ethanol-induced ulcerative process. Methods: in this study, ulcer induction models by absolute ethanol were used in Wistar rats previously treated with Indomethacin (5mg/kg of body weight), N-ethylmaleimide (10mg/kg of body weight), and L-NAME (5mg/kg of body weight). Within the same ulcer induction model, the administration of the following was performed: saline solution (10 mL/kg of body weight) as a negative control, Carbenoxolone (200mg/kg) as a positive control, and the fermented product at a dose of 2,000mg/kg of body weight. Results: when verifying the antiulcerogenic activity of the fermented powder, the Ulcerative Lesion Index (ULI) was inhibited by 29.9%, while the Carbenoxolone used as a positive control was able to inhibit the ULI by 83.7%. In the ulcer induction model by absolute ethanol, with previous administration of L-NAME, N-ethylmaleimide, and Indomethacin, it was verified that with the first two treatments the fermented powder showed 50.9% and 28.3% antiulcerogenic activity, respectively, and no antiulcerogenic activity with the Indomethacin treatment, which suggests that its mechanism of action occurs through the synthesis or degradation reduction of prostaglandins responsible, along with other factors, for the gastric cytoprotection. Conclusion: based on the data from this trial with rats to evaluate the antiulcerogenic activity and mechanism of action of the fermented product, it was concluded that it probably promotes gastric cytoprotection, mainly through prostaglandin levels.

In vitro and in vivo anticancer activity of extracts, fractions, and eupomatenoid-5 obtained from Piper regnellii leaves.

Despite numerous studies with the Piper genus, there are no previous results reporting in vitro or in vivo Piper regnellii (Miq.) C. DC. var. regnellii anticancer activity. The aim of this study was to investigate P. regnellii in vitro and in vivo anticancer activity and further identify its active compounds. In vitro antiproliferative activity was evaluated in 8 human cancer cell lines: melanoma (UACC-62), breast (MCF7), kidney (786-0), lung (NCI-H460), prostate (PC-3), ovary (OVCAR-3), colon (HT29), and leukemia (K-562). Total growth inhibition (TGI) values were chosen to measure antiproliferative activity. Among the cell lines evaluated, eupomatenoid-5 demonstrated better in vitro antiproliferative activity towards prostate, ovary, kidney, and breast cancer cell lines. In vivo studies were carried out with Ehrlich solid tumor on Balb/C mice treated with 100, 300, and 1000 mg/kg of P. regnellii leaves dichloromethane crude extract (DCE), with 30 and 100 mg/kg of the active fraction (FRB), and with 30 mg/kg of eupomatenoid-5. The i. p. administration of DCE, FRB, and eupomatenoid-5 significantly inhibited tumor progression in comparison to control mice (saline). Therefore, this study showed that neolignans of Piper regnellii have promising anticancer activity. Further studies will be undertaken to determine the mechanism of action and toxicity of these compounds.

Efeitos da administração aguda e subcrônica da Luehea divaricata Martus et Zuccarini / Effects of acute and subchronic administration of Luehea divaricata Martus et Zuccarini

As cascas de Luehea divaricata Martus et Zuccarini (Tiliaceae) são usadas na medicina popular como antinflamatório e como anti-rumático. O objetivo deste trabalho foi determinar o efeito toxicológico subcrônico do extrato bruto hidroalcoólico (70 por cento) (CHE) em ratos, pela via oral e intraperitonial.

Antiulcerogenic activity of some sesquiterpene lactones isolated from Artemisia annua.

Artemisinin 1, dihydro-epideoxyarteannuin B 2 and deoxyartemisinin 3 were isolated from the sequiterpene lactone-enriched fraction obtained from the crude ethanolic extract of Artemisia annua L. These compounds were tested on ethanol and indomethacin-induced ulcer models. Compound 1 did not afford cytoprotection under the experimental models tested. Only compounds 2 and 3 decreased the ulcerative lesion index produced by ethanol and indomethacin in rats. These compounds did not demonstrate antiulcerogenic activity when tested on the ethanol-induced ulcer model, with previous administration of indomethacin, suggesting that the antiulcerogenic activity is a consequence of prostaglandin synthesis increase.