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

• Grant number: 20/01080-1
• Support Opportunities: 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 Investigator: Luís Fernando Barbisan
• Grantee: Sara Gomes Espírito Santo
• Host 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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANTO, SARA GOMES ESPIRITO; MONTE, MARINA GAIATO; POLEGATO, BERTHA FURLAN; BARBISAN, LUIS FERNANDO; ROMUALDO, GUILHERME RIBEIRO. Protective Effects of Omega-3 Supplementation against Doxorubicin-Induced Deleterious Effects on the Liver and Kidneys of Rats. Molecules, v. 28, n. 7, p. 14-pg., 2023-04-01. (20/01080-1)