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OBJECTIVE: The study's aim was to evaluate Brazilian Brown Propolis (BBP) and Artepillin C (ARC) chemopreventive action in Wistar rats' colons. METHODS: Fifty male Wistar rats were divided into ten experimental groups, including control groups, groups with and without 1,2-dimethylhydrazine (DMH) induction, and BBP, ARC, and ARC enriched fraction (EFR) treatments, for sixteen weeks. Aberrant crypt foci (ACF) were classified as hyperplastic or dysplastic, and proliferating cell nuclear antigen (PCNA) expression was quantified. RESULT: ACF amounts in experimental groups (induced or not) decreased in both colon portions, while the isolated Aberrant Crypt (AC) number increased. Experimental groups of animals showed higher hyperplasia and dysplasia amounts compared with control groups. The ACF dysplastic amount present in groups induced and treated, in both colon portions, had similar values to IDMH (DMH induction group without treatment). In addition, DMH was effective in ACF inducing and there was positive staining for PCNA in basal and upper dysplastic foci portions in all experimental groups, in the mitotic index (MI) evaluation. To conclude, considering all the experimental groups, the one treated with EFR (fraction enriched with ARC) had the lowest rates of cell proliferation. CONCLUSION: BBP and its derivatives prevented crypt cell clonal expansion.

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Although studies show that pesticides, especially insecticides, may be toxic to humans, publications on the neurological effects of fungicides are scarce. As fungicides are used widely in Brazil, it is necessary to gather evidence to support actions aimed at safely using of these chemicals. We investigated through a systematic review of publications on the use of fungicides and consequences of exposure related to nervous system diseases or neurological disorders in humans. The protocol review was registered on PROSPERO and followed the guidelines of the PRISMA-Statement. As far as it is known, there is no apparent systematic review in the literature on this topic. The search was comprised of the following databases: PubMed; Web of Science; Scopus and EMBASE, using groups of Mesh terms and strategies specific to each database. Thirteen articles were selected for this review. Regarding the substances analyzed in the studies, some reported the use of fungicides in general, without separating them by type, while others summarized the categories of all pesticides by their function (insecticides, herbicides, fungicides, etc.) or chemical class (dithiocarbamate, dicarboximide, inorganic, etc.). However, most of the articles referred to fungicides that contain the metal manganese (Mn) in their composition. As for neurological disorders, articles addressed Parkinson's disease (PD), neurodevelopmental outcomes, extrapyramidal syndrome resembling PD, cognitive disorders, depression, neural tube defects, motor neurone disease, and amyotrophic lateral sclerosis. Most investigations pointed to exposure to fungicides, mainly maneb and mancozeb, leading to the development of at least one neurological disease, which suggests the need for further multicentric clinical trials and prospective studies for greater clarity of the research problem.

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Abstract Aims: To identify the histopathological alterations in organs of Wistar rats to evaluate toxic effects of use of Annonamuricata Raw Leaf Extract (AMRLE) alone or in association with DMBA. Settings and Design: Sixty female Wistar rats were used, separated into groups and treated with a single dose of 65 mg/kg of DMBA and/or with 50; 100 and 200 mg/kg of AMRLE. Hematoxylin-Eosin (HE) and 1% methylene blue stains were used in the histopathological analysis and quantification of Aberrant Crypts (ACs) and Aberrant Crypt Focus (ACF). Fischer and Kruskal Wallis tests were used in the statistical analysis. Results: The administration of 65 mg/kg of DMBA and/or 50, 100 and 200 mg/kg of AMRLE did not influence weight development. Some histopathological alterations (hepatic steatosis; inflammatory foci in the liver, kidney and lung; pulmonary lymphoid hyperplasia, ectasia and hyperplasia in mammary gland epithelium) and the development of ACs and ACF in the intestinal colon were observed in all groups, except in the group negative control, with no statistical difference between analysed groups. Conclusions: Histopathological alterations and the formation of ACs and ACF did not show a statistically significant difference between the groups analysed. However, although AMRLE has antioxidant effects due to the presence of phenolic components, there was still the formation of some pathological processes that may be related to the isolated toxic action of DMBA and/or associated with other components of AMRLE, since these changes were not seen in the negative control group.

Resumen Objetivos: Identificar las alteraciones histopatológicas en órganos de ratas Wistar para evaluar los efectos tóxicos del uso del Extracto de Hoja Cruda de Annona muricata (AMRLE) solo o en asociación con DMBA. Configuración y diseño: Se utilizaron sesenta ratas hembras Wistar, se separaron en grupos y se trataron con una dosis única de 65 mg/kg de DMBA y/o con 50, 100 y 200 mg/kg de AMRLE. Se utilizaron tinciones de hematoxilina-eosina (HE) y azul de metileno al 1% en el análisis histopatológico y la cuantificación de criptas aberrantes (CA) y focus de criptas aberrantes (FCA). En el análisis estadístico se utilizaron las pruebas de Fischer y Kruskal Wallis. Resultados: La administración de 65 mg/kg de DMBA y/o 50, 100 y 200 mg/kg de AMRLE no influyó en el desarrollo del peso. Se observaron algunas alteraciones histopatológicas (esteatosis hepática; focus inflamatórios en el hígado, riñón y pulmón; hiperplasia, ectasia en epitelio de la glándula mamaria e hiperplasia linfoide pulmonar) y el desarrollo de CA y FCA en el colon intestinal en todos los grupos, excepto en el grupo control negativo, sin diferencias estadísticas entre los grupos analizados. Conclusiones: Las alteraciones histopatológicas y la formación de CA y FCA no mostraron diferencias estadísticamente significativas entre los grupos analizados. Sin embargo, aunque AMRLE tiene efectos antioxidantes debido a la presencia de componentes fenólicos, aún existe la formación de algunos procesos patológicos que pueden estar relacionados con la acción tóxica aislada del DMBA y/o asociados con otros componentes de AMRLE, ya que estos cambios no fueron observados en el grupo control negativo.

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INTRODUCTION: Aberrant Crypt (AC) and Aberrant Crypt Focus (ACF) are considered pre-neoplasic lesions, ranging from hyperplasia to different degrees of dysplasia in the colon. This work aimed to evaluate and quantify the chemopreventive activity of Zingiber officinale essential oil in the colorectal region of Wistar rats. MATERIALS AND METHODS: We extracted the essential oil from ginger rhizomes and carried out ACF induction, in rats, with 1.2 Dimethylhydrazine (DMH) at a 20 mg/kg dose. The experimental groups were GI (negative control); GII (positive induction control); GIII (DMH + essential oil); GIV (DMH +5-Florouracil) and GV (essential oil). The histological techniques used were methylene blue, hematoxylin-eosin (HE) dyeing, and immunohistochemistry (IHQ). RESULTS: The major essential oil compounds were citral (17.25%), δ-citral (10.25%), camphene (9.55%), α-zingiberene (7.57%), nerol (6.37%) and plelandrene (6.83%). For the presence of AC or ACF, we did not observe them in GI and GV, while in GII and GIII, they were observed, in high values, in both regions, but only in the distal region, there was a significant difference between them. For GIV, for both regions, there were significant lower numbers of AC when compared to GIII. As observed, with HE, there were hyperplastic and dysplastic ACF in the proximal and distal portions of the colon. For IHQ analyses, there were positively PCNA antibody marked cells in all experimental groups. Yet, there was no significant correlation of mitotic index among them. Moreover, the results of GIII compared to GIV were very similar. CONCLUSION: In this sense, the Zingiber officinale essential oil has good antioxidant potential because it presents a mixture of monoterpene and sesquiterpene compounds. Thus, it is able to develop a chemoprotective effect, as it presented similar results to the standard drug, showing cell proliferation control.

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