The potential toxic effects of chronic doxorubicin treatment on the rat pancreas and the role of ghrelin in this context
Year: 2018
Type: dissertation
Abstract: Introduction: Doxorubicin (DOX), is a chemotherapeutic drug that has potent antineoplastic actions.It is for this reason that it remains one of the most widely used chemotherapeutic agents that has led to an increase in the survival rates of cancer patients.However, DOX's efficacy in treating a variety of cancers is a double-edged sword due to its cumulative, dose-dependent toxicity, particularly in cardiomyocytes.Since DOX's anti-neoplastic activities are separate to the mechanisms underlying its toxicity, there is a need to investigate adjuvant therapies that do not interfere with DOX's ability to kill cancerous cells, but have the potential to protect against its toxicity.Ghrelin, a brain-peptide commonly known for its appetite inducing and growth hormone (GH) releasing actions, has previously been shown to reduce oxidative stress, apoptosis, inflammation and fibrosis, all of which contribute to DOX-induced toxicity, in different contexts.However, over the years, literature has predominantly focused on DOX's effects on the heart, while very few studies are available regarding DOX's effects on the pancreas.Therefore, this study investigated the effects of DOX on the pancreas and whether ghrelin can provide protection against these effects in a model of chronic DOX-induced cardiotoxicity. Materials and Methods:Male Sprague-Dawley were randomly divided into four treatment groups.The vehicle group received 200 μl of physiological saline, the ghrelin group received 100 µg/kg three times a week, the DOX group received 2.5 mg/kg once a week, and the combination group (DOX+ghrelin) received both treatment regimens.All treatments were conducted via intraperitoneal injection over a period of eight weeks.A week after the last injection, animals were euthanised, blood was collected, and organs were harvested.After the pancreata were weighed, they were nonspecifically divided into two sections, where one half was presevered in 4% formaldehyde solution for histological analysis, and the other half was snap frozen in liquid nitrogen for biochemical analysis.Serum inflammatory markers as well as pancreatic hormones insulin and glucagon were measured using a multiplex assay.General morphological changes, collagen deposition, and the number of α-and β-cells were assessed by employing H&E, Masson's Trichrome, and immunohistochemical stains, respectively.In addition to lipid peroxidation, oxidative stress was assessed by the ORAC, SOD and glutathione assays.Finally, Western blotting was utilised to determine the expression of the apoptotic marker, cleaved caspase-3.
Author: Kirsten Lee Scott
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2799545311