Effect of gamma-oryzanol (yOz) on doxorubicin-induced acute toxicity in soleus muscle of rats

• Grant number: 21/11369-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2022
• End date: March 31, 2023
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Camila Renata Corrêa
• Grantee: Aline Campos de Souza
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The chemotherapy doxorubicin (DOX) is important in the treatment of neoplasms because of its action on the DNA. However, the continuous use of this drug has adverse effects on patients, including toxicity on the soleus muscle. Therefore, since the soleus muscle is considered a sensitive model to oxidative stress and has various structural and metabolic functions, it is necessary to investigate some mechanisms that lead to this toxicity, so that the development of prevention therapies is possible in patients with cancer who use this medication. This way, the objective of this work will be to verify the effect of yoZ on the acute toxicity induced by doxorubicin in the soleus muscle of rats. Male Wistar rats (n=32) will be initially randomized into two groups: Control (C, n=16) which will receive daily corn oil by gavage, and the yOz group (G, n=16), which will receive daily yOz, at a concentration of 381mg/Kg, diluted in corn oil also via gavage. Seven days after this procedure, the animals will be redistributed again into four groups: The animals in the control group (n=16) will receive: Control (C, n=8), intraperitoneal injection with PBS and DXO (D, n=8 ) intraperitoneal injection of 4mg/Kg of DXO (Doxorubicin Hydrochloride (Rubidox) from the Chemical Pharmaceutical Laboratory Bergamo Ltda); animals in the yOz group (n=16) will receive: yOz (n=8) intraperitoneal injection (IP) with PBS and yOz + DXO (n=8), intraperitoneal injection of 4mg/Kg of DXO. 24 hours after this procedure, the animals will be anesthetized (IP) with ketamine hydrochloride 200mg/kg + xylazine 30mg/kg and then euthanized. Blood and soleus muscle will be collected for analysis. The bioavailability of yOz in plasma and soleus muscle will be evaluated by high-performance chromatography (HPLC). In muscle, hydrophilic antioxidant capacity, lipid oxidative damage (malondialdehyde), and protein carbonylation will be evaluated. Statistical analysis will be performed using SigmaStat version 2.0 (JandelScientific Software, San Rafael, CA, USA). Parametric data will be presented as mean ± standard deviation and comparisons between groups will be performed by parametric analysis of variance (ANOVA) and complemented with Bonferroni's posthoc test. Non-parametric data will be presented as median and interquartile (p25 and p75) and the test to be used will be the Kruskal-Wallis, complemented by Dunn's posthoc test. Differences will be considered significant when p < 0.05. The study was approved by the local ethics committee under number 1336/2019.(AU)