Effects of oral administrated capsaicin in the intestinal mucositis induced by the chemotherapy drug irinotecan hydrochloridrate (CPT-11) in C57BL/6J mice

• Grant number: 23/02741-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: May 31, 2024
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Luís Fernando Barbisan
• Grantee: Daniela Kuniyoshi
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Malignant neoplasms hold the second place among the main causes of mortality worldwide, and the main therapeutic alternatives include surgical interventions, radiotherapy and chemotherapy. Although these interventions are beneficial, they result in many side effects that reduce their efficiency and increase treatment costs. Among the adverse effects of the use of chemotherapy drugs, the intestinal mucositis is one of them and little is known about how bioactive food components (BFCs) can interfere with its clinical evolution. Among the BFCs, capsaicin (CAP) is the main alkaloid responsible for the pungency of Capsicum genus fruits, which includes several peppers and hot peppers species used in cooking. Thus, this study will evaluate whether CAP oral administration interferes with the evolution of intestinal mucositis induced irinotecan (CPT-11). Thus, male C57BL/6J mice will be allocated into five groups: Group 1 (n=8) - single doses of CPT-11 (75 mg/kg, intraperitoneally (i.p.) and corn oil (CAP vehicle) by intragastric administration (i.g.) for six consecutive days; Groups 2 and 3 (n=8/each) - single doses of CPT-11 (75 mg/kg, i.p.) and CAP (12.5 and 25 mg/kg, i.g.), respectively, for six consecutive days; Group 4 (n=5) - single doses of saline (CPT-11 vehicle, i.p.) and CAP (25 mg/kg, i.g.) for six consecutive days; Group 5 (n=5) - single doses of saline solution (CPT-11 vehicle, i.p.) and corn oil (CAP vehicle, i.g.) for six consecutive days. Peripheral blood samples will be collected from the retro-orbital plexus, four hours after the last IRT application for DNA damage analysis in leukocytes (Comet assay). In the following day, the animals will be euthanized, and blood (serum), liver, kidneys and intestines will be collected and processed histologically. Small intestine samples will be stored (-80ºC) for myeloperoxidase activity analysis. Hematoxylin and eosin (HE)-stained liver and kidney sections will be analyzed for the evidence of toxicity, along with the determination of alanine aminotransferase (ALT) and creatinine and urea plasma levels. Histopathologic and morphometric (villi and crypt height) analysis will be performed on the small intestine (duodenum and ileum) and large intestine (proximal colon) in HE-stained sections. Other sections will be stained with Schiff periodic acid/Alcian blue, and goblet cells will be counted in these intestinal segments. Immunohistochemistry will also be performed for Ki-67(cell proliferation), ³H2Ax (DNA damage), and CD68 (macrophages) in intestine sections.