Effects of Wasabi (Wasabia japonica) and allyl isothiocyanate on irinotecan (CPT-11)-induced intestinal mucositis in rodents

• Grant number: 23/06144-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2023
• End date: September 30, 2024
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Luís Fernando Barbisan
• Grantee: Ana Clara Gemignani
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Irinotecan hydrochloride (CPT-11) is widely used for the treatment of various malignant neoplasms. CPT-11 is responsible for several side effects, including intestinal mucositis (IM). During CPT-11-induced MI, it would be important to assess how foods or bioactive/nutraceutical compounds can influence its evolution. Wasabi (Wasabia japonica), especially its rhizome, is widely used as an ingredient in oriental cuisine. Wasabi has already demonstrated in vivo and in vitro anti-inflammatory effects, which can be attributed to its most abundant bioactive compound, allyl isothiocyanate (AITC), or to the combination of various compounds in the rhizome. Thus, for the first time, we will evaluate whether wasabi or AITC attenuates the development of CPT-11-induced IM in rodents. Thus, female C57BL6/J mice will receive daily single doses of CPT-11 (75 mg/kg body weight, intraperitoneal) for 5 days, and will be treated with daily single doses of wasabi (0.5 or 1 g/kg body weight, intragastric) or AITC (dose to be determined) also for 5 days. AITC will be proportional to the amount of this same compound in the wasabi, which will be determined by gas chromatography-mass spectrometry (GC/MS). Peripheral blood samples will be collected for genotoxicity analysis, while serum will be analyzed for alanine aminotransferase, urea and creatinine. Histopathological and morphometric analyses (hematoxylin and eosin) will be performed on small intestine and colon tissue slides, as well as counting of goblet cells (periodic acid-Schiff/Alcian blue) and determination of Ki-67 (cell proliferation), ³H2Ax (DNA damage), and CD68 (macrophages) markers by immunohistochemistry. Other samples of small intestine will be used for myeloperoxidase activity analysis and immunoblotting for Nrf2 and p65.