Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways

Alzheimer’s disease (AD) is a devastating illness with limited therapeutic interventions. The aim of this study is to investigate the pathophysiological mechanisms underlying AD and explore the potential neuroprotective effects of cocoa, either alone or in combination with other nutraceuticals, in an animal model of aluminum-induced AD. Rats were divided into nine groups: control, aluminum chloride (AlCl3) alone, AlCl3 with cocoa alone, AlCl3 with vinpocetine (VIN), AlCl3 with epigallocatechin-3-gallate (EGCG), AlCl3 with coenzyme Q10 (CoQ10), AlCl3 with wheatgrass (WG), AlCl3 with vitamin (Vit) B complex, and AlCl3 with a combination of Vit C, Vit E, and selenium (Se). The animals were treated for five weeks, and we assessed behavioral, histopathological, and biochemical changes, focusing on oxidative stress, inflammation, Wnt/GSK-3β/β-catenin signaling, ER stress, autophagy, and apoptosis. AlCl3 administration induced oxidative stress, as evidenced by elevated levels of malondialdehyde (MDA) and downregulation of cellular antioxidants (Nrf2, HO-1, SOD, and TAC). AlCl3 also upregulated inflammatory biomarkers (TNF-α and IL-1β) and GSK-3β, leading to increased tau phosphorylation, decreased brain-derived neurotrophic factor (BDNF) expression, and downregulation of the Wnt/β-catenin pathway. Furthermore, AlCl3 intensified C/EBP, p-PERK, GRP-78, and CHOP, indicating sustained ER stress, and decreased Beclin-1 and anti-apoptotic B-cell lymphoma 2 (Bcl-2) expressions. These alterations contributed to the observed behavioral and histological changes in the AlCl3-induced AD model. Administration of cocoa, either alone or in combination with other nutraceuticals, particularly VIN or EGCG, demonstrated remarkable amelioration of all assessed parameters. The combination of cocoa with nutraceuticals attenuated the AD-mediated deterioration by modulating interrelated pathophysiological pathways, including inflammation, antioxidant responses, GSK-3β-Wnt/β-catenin signaling, ER stress, and apoptosis. These findings provide insights into the intricate pathogenesis of AD and highlight the neuroprotective effects of nutraceuticals through multiple signaling pathways

Chronic toxicity test with sea urchin Echinometra lucunter and Lytechinus variegatus (Echinodermata: Echinoidea), exposed to light-stick - flag paternoster used for longline surface fishing

In this work, the chronic toxicity of a mixture of light-stick chemicals and water was tested. The light-stick is used in fishery activities to catch swordfish. The tubes were collected on the beaches of the Costa dos Coqueiros - BA, Brazil, in the period from 14th to 31st July 2007. The method used was a short chronic toxicity test where embryos of the sea urchins Echinometra lucunter and Lytechinus variegatus were exposed to a stock solution consisting of the supernatant formed from a mixture of sea water and the orange-colored light-stick chemical. After a preliminary test, concentrations defined were 0.002, 0.003, 0.01, 0.02, 0.1, 1.0% of stock solution. The final test ran for 36 hours for E. Lucunter and 24 hours for L. variegatus with 4 replicates for each concentration. The value of EC50 - 36h was 0.062% with confidence limits ranging from 0.042 to 0.079% and the EC50 - 24h was 0.011% with confidence limits ranging from 0.009 to 0.014%, i.e., the chemical mix present in the light-stick is potentially toxic. So, as these flags are commonly used for fishing there is potential danger in their disposal in the open ocean.<br>O objetivo deste trabalho foi avaliar a toxicidade crônica da água do mar em contato com o líquido contido no light-stick, sinalizador utilizado em pesca de espinhel de superfície para a captura de espadarte. Os tubos foram coletados nas praias da Costa dos Coqueiros - BA, no período de 14 a 31 de Julho de 2007. O método utilizado para a verificação da toxicidade crônica foi o teste de curta duração com embriões de ouriço-do-mar Echinometra lucunter e Lytechinus variegatus, os ensaios foram realizados com solução estoque que consiste do sobrenadante formado a partir de uma mistura de água do mar com o líquido do sinalizador de coloração laranja. Após um teste preliminar as concentrações definidas foram 0.002; 0.003; 0.01; 0.02; 0.1; 1.0%. O teste definitivo teve duração de 36 horas para E. lucunter e 24 horas para L. variegatus, sendo preparadas 4 réplicas para cada concentração. O valor da CE50 - 36h encontrado foi de 0.062% com limites de aceitabilidade variando de 0.042 a 0.079% e a CE50 - 24h encontrada foi de 0.011% com limites de aceitabilidade variando de 0.009 a 0.014%, ou seja, os compostos químicos presentes no light-stick são potencialmente tóxicos. Portanto já que esses sinalizadores são utilizados comumente como petrechos de pesca há a necessidade de que eles sejam recolhidos, pois podem causar efeitos adversos quando abrem nos oceanos