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Study of the influence of diterpene manool on doxorubicin-induced genotoxicity and its relation to NF-kB gene expression

Grant number: 19/06903-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2019
Effective date (End): December 31, 2020
Field of knowledge:Health Sciences - Pharmacy - Toxicological Analysis
Principal Investigator:Denise Crispim Tavares Barbosa
Grantee:Tabata Rodrigues Esperandim
Home Institution: Pró-Reitoria Adjunta de Pesquisa e Pós-Graduação. Universidade de Franca (UNIFRAN). Franca , SP, Brazil

Abstract

Salvia officinalis L. is a woody perennial subshrub, native to the Mediterranean region, popularly known as sage. This species is widely distributed in the world and can be used in both culinary and medicinal preparations. S. officinalis presents different biological properties, such as: antispasmodic, antimicrobial, anti-inflammatory and carminative. Among the most abundant metabolites of S. officinalis, the diterpene manool is outstanding, which demonstrated a selective cytotoxic effect between normal and tumoral cell lines. In addition, it presented chemopreventive effect against mutagenic methyl methanesulfonate induced damage in human hepatocarcinoma cell line (HepG2). Therefore, in view of the biological properties of S. officinalis and diterpene manool, one of its major substances, the present work aims to evaluate the influence of manool on the genotoxicity induced by doxorubicin (DXR) in Swiss mice, as well as to study the its mechanism of action by analyzing the expression of the NF-kB gene in renal tissue. In addition, the study aims to evaluate the hepatotoxicity of the manool and/or DXR treatments through the biochemical measurement of serum levels of the alanine aminotransferase and aspartate aminotransferase enzymes. The peripheral blood micronucleus test will be used to study the cytotoxic, genotoxic and antigenotoxic effect of manool. The animals will be treated with three different doses of manool (low, intermediate and high) followed by administration of the DXR. Genotoxicity and antigenotoxicity will be assessed by the frequency of micronucleated polychromatic erythrocytes. The cytotoxicity of the treatments will be evaluated considering the ratio of polychromatic erythrocytes to total erythrocytes. Analysis of NF-kB gene expression in renal tissue of animals submitted to different treatments will be conducted by immunohistochemistry. Therefore, the study in question will allow a better understanding of the action of manool in the organism, becoming possible the safe and effective use in future therapeutic applications.