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Effects of omega 3 supplementation on hepatotoxicity and nephrotoxicity induced by doxorubicin in Wistar rats

Grant number: 20/01080-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2020
Effective date (End): February 28, 2021
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal researcher:Luís Fernando Barbisan
Grantee:Sara Gomes Espírito Santo
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The use of the doxorubicin (DOX) chemotherapy, frequently recommended to the treatment of many types of human solid tumors, leads to several side effects, including cardiotoxicity, hepatotoxicity and nephrotoxicity. The increased oxidative stress is the main DOX-related mechanism of toxicity. On the other hand, the search for dietary interventions in order to attenuate DOX-induced side effects is still relevant. Therefore, the study will evaluate the protective effects of omega 3 (É-3) supplementation on DOX-induced hepatotoxicity and nephrotoxicity in rats. Wistar male rats (n=40) will be allocated in 4 experimental groups (10 animals/group): control, É-3, DOX and DOX+É-3. The É-3 (400 mg/kg/day) will be daily administered via gavage for six consecutive weeks. After the two fist weeks of É-3 administration, there will be a single DOX administration (3.5 mg/kg, intraperitoneal, 1x/week) for four weeks, totalizing 6 weeks of experiment. At the end of the experiment, the animals will be euthanized, and blood, liver and kidney samples will be collected. The genotoxicity (comet assay) will be evaluated in peripheric blood samples and biochemical analyses will be performed in serum (alanine aminotransferase, creatinine and urea). Liver and kidney will be sampled for collagen morphometry (Picro Sirius red), and histopathological (HE) and immunohistochemical (Ki-67, i.e. proliferation, phosphorylated histone H2A.X, i.e. DNA damage and caspase-3, i.e. apoptosis) analysis. Lipid hydroperoxide, and Bcl-2, NF-ºB and Nrf2 (immunoblotting) also will be evaluated in both liver and kidney. Incidence data will be analyzed by Chi-square test or Fisher's exact test. Other data will be analyzed by One-Way ANOVA or Kruskal-Wallis. The level of significance adopted will be p<0,05.

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