Pre-Treatment with Amifostine Protects against Cyclophosphamide-Induced Disruption of Taste in Mice

Nabanita Mukherjee,Jeffrey L Spees,Brittany L Carroll,Eugene R Delay,John I Glendinning

doi:10.1371/journal.pone.0061607

Abstract

Cyclophosphamide (CYP), a commonly prescribed chemotherapy drug, has multiple adverse side effects including alteration of taste. The effects on taste are a cause of concern for patients as changes in taste are often associated with loss of appetite, malnutrition, poor recovery and reduced quality of life. Amifostine is a cytoprotective agent that was previously shown to be effective in preventing chemotherapy-induced mucositis and nephrotoxicity. Here we determined its ability to protect against chemotherapy-induced damage to taste buds using a mouse model of CYP injury. We conducted detection threshold tests to measure changes in sucrose taste sensitivity and found that administration of amifostine 30 mins prior to CYP injection protected against CYP-induced loss in taste sensitivity. Morphological studies showed that pre-treatment with amifostine prevented CYP-induced reduction in the number of fungiform taste papillae and increased the number of taste buds. Immunohistochemical assays for markers of the cell cycle showed that amifostine administration prevented CYP-induced inhibition of cell proliferation and also protected against loss of mature taste cells after CYP exposure. Our results indicate that treatment of cancer patients with amifostine prior to chemotherapy may improve their sensitivity for taste stimuli and protect the taste system from the detrimental effects of chemotherapy.

Highlights

Chemotherapy for cancer often has side effects such as alopecia, nausea, nephrotoxicity and taste alterations [1,2]
AMF protects against CYP-induced deficits in taste sensitivity Existing clinical literature suggests that chemotherapy drugs may elevate taste thresholds [8]
Our behavioral data revealed two periods of taste deficits after CYP administration, we examined the lingual epithelium for potential changes that might correspond to the observed disruptions in taste function

Summary

Introduction

Chemotherapy for cancer often has side effects such as alopecia, nausea, nephrotoxicity and taste alterations [1,2]. Cyclophosphamide (CYP), a chemotherapy drug, is prescribed worldwide for various types of cancer either by itself or in combination with other drugs [3]. As a DNA-alkylating agent, CYP can damage the DNA of target cells by forming intra-strand or inter-strand cross linkages [4,5]. Proliferating cells are especially sensitive to CYP due to conformational changes in DNA. CYP affects healthy normal cells undergoing division as well as rapidly proliferating cancerous cells.

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Conclusion