Effect of Citrus Bergamia by-product on systemic oxidative damage triggered by acute dose of doxorubicin

• Grant number: 23/09457-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2023
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Camila Renata Corrêa
• Grantee: Felipe Berretta
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Cancer is one of the leading causes of death worldwide. In Brazil, an increase in the rate of cases of the disease is estimated, making the search for efficient therapeutic strategies relevant. Among the treatments, doxorubicin (DOX) is an effective and widely used drug, but its toxicity causes great concern, since it affects several organs such as the heart, liver and kidneys. Oxidative stress is pointed out as one of the main mechanisms of DOX toxicity, therefore, in the search to reduce the toxic effects of this drug, researchers have evaluated the intervention with bioactive compounds derived from plants, such as flavonoids and carotenoids, which have antioxidant properties. Citrus bergamia has shown antioxidant and anti-inflammatory potential in in vitro and in vivo studies. Therefore, the objective of this work is to verify the systemic antioxidant effect of the by-product of Citrus bergamia (Endoberg®) in an acute experimental model of doxorubicin. Wistar rats will be initially randomized into two groups: Control (C, n=16) that will receive drinking water daily by gavage, and the Citrus bergamia group, commercially called Endoberg® (CE, n=16), that will receive this citrus daily in the concentration of 250 mg/Kg, diluted in drinking water also via gavage. Seven days after the treatments, the animals will be redistributed into four groups again: Control (C, n=8), intraperitoneal injection with PBS; DOX group (D, n=8), intraperitoneal injection of 4mg/Kg of DOX (Doxorubicin Hydrochloride (Rubidox) from the Pharmaceutical Chemical Laboratory Bergamo Ltda); CE (n=8), intraperitoneal (IP) injection with PBS; and CE + DOX (n=8), intraperitoneal injection of 4mg/Kg of DOX. 48 hours after this procedure, the animals will be anesthetized (IP) with ketamine hydrochloride 200mg/kg + xylazine 30mg/kg and then euthanized. Blood, liver, kidneys and heart will be collected for oxidative stress analysis such as: lipid peroxidation by malondialdehyde, protein carbonylation and oxidation, antioxidant capacity and tissue morphology by hematoxylin and eosin (HE) staining. Parametric data will be presented as mean ± standard deviation and comparisons between groups will be performed by two-way ANOVA with Tukey's post-hoc test. Nonparametric data will be presented as median and interquartile semi-range and comparisons between groups will be performed using the Kruskal-Wallis test with Dunn's post-hoc test. P values <0.05 will be considered statistically significant. Statistical analysis will be performed using SigmaStat software version 3.5 (Systat Software Inc., San Jose, California, United States).