Cyclophosphamide-induced disruption of umami taste functions and taste epithelium

• Published in: Neuroscience Vol. 192; pp. 732 - 745
• Main Authors: Mukherjee, N, Delay, E.R
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 29-09-2011; Elsevier
• Subjects: animal psychophysics; Animals; Antineoplastic Agents - toxicity; Biological and medical sciences; chemotherapy; Cyclophosphamide - toxicity; cytotoxicity; Fundamental and applied biological sciences. Psychology; Male; Mice; Mice, Inbred C57BL; Neurology; Olfactory system and olfaction. Gustatory system and gustation; Taste - drug effects; taste acuity; Taste Buds - drug effects; taste cell renewal; umami; Vertebrates: nervous system and sense organs; MSG; TSC; umami; inosine 5′-monophosphate; conditioned taste aversion; chemotherapy; IMP; animal psychophysics; taste acuity; stimulus associated with reinforcement; stimulus associated with punishment; CTA; S; taste cell renewal; ANOVA; taste sensory cell; cyclophosphamide; monosodium glutamate; CYP; cytotoxicity; Analysis of variance; Chemotherapy; Cyclophosphamide; Treatment; Gustation; Cytotoxicity; Taste; Gustative system; Psychophysics
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2011.07.006

Abstract Clinical studies have reported taste dysfunctions developing in patients undergoing chemotherapy. This adverse side effect is a major concern for the doctors and patients because disrupted taste can reduce appetite, cause malnutrition, delay recovery, and affect quality of life. Cyclophosphamide (CYP) is a common atenoplastic drug used during chemotherapy and is thought to affect taste through learned tasted aversions. This study asked whether CYP also alters umami taste sensory functions and disrupts taste epithelium of mice. Behavioral tests focused on taste acuity, assessed by the ability of mice to discriminate between the taste qualities of two umami substances, monosodium glutamate (MSG) and inosine 5′-monophosphate (IMP), and taste sensitivity, assessed by detection thresholds of MSG and IMP, after an IP injection (75 mg/kg) of CYP. The behavioral results revealed a two-phase disturbance in taste acuity and loss of sensitivity, the first phase occurring within 2–4 days after injection and the second occurring 9–12 days after injection. The number of fungiform papillae (with and without pores) decreased immediately after injection and did not begin to recover until 12 days after injection. Circumvallate taste buds began to show disturbances by 8 days after injection and evidence of recovery beginning 12 days after injection. Von Ebner glands were smaller and secreted less saliva 4 days postinjection but not later. These findings suggest the initial behavioral deficits may be because of cytotoxic effects of the drug on taste sensory tissues, whereas the second phase may be because of a disturbance of the taste cell replacement cycle.