Cyclophosphamide and the taste system: Effects of dose fractionation and amifostine on taste cell renewal.
Amifostine
/ pharmacology
Animals
Antineoplastic Agents
/ administration & dosage
Cell Count
Cell Proliferation
/ drug effects
Cyclophosphamide
/ administration & dosage
Dose-Response Relationship, Drug
Humans
Immunohistochemistry
Male
Mice
Mice, Inbred C57BL
Phospholipase C beta
/ metabolism
Protective Agents
/ pharmacology
Synaptosomal-Associated Protein 25
/ metabolism
Taste
/ drug effects
Taste Buds
/ drug effects
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
31
01
2019
accepted:
22
03
2019
entrez:
5
4
2019
pubmed:
5
4
2019
medline:
3
1
2020
Statut:
epublish
Résumé
Chemotherapy often causes side effects that include disturbances in taste functions. Cyclophosphamide (CYP) is a chemotherapy drug that, after a single dose, elevates murine taste thresholds at times related to drug-induced losses of taste sensory cells and disruptions of proliferating cells that renew taste sensory cells. Pretreatment with amifostine can protect the taste system from many of these effects. This study compared the effects of a single dose (75 mg/kg) of CYP with effects generated by fractionated dosing of CYP (5 doses of 15 mg/kg), a dosing approach often used during chemotherapy, on the taste system of mice using immunohistochemistry. Dose fractionation prolonged the suppressive effects of CYP on cell proliferation responsible for renewal of taste sensory cells. Fractionation also reduced the total number of cells and the proportion of Type II cells within taste buds. The post-injection time of these losses coincided with the life span of Type I and II taste cells combined with lack of replacement cells. Fractionated dosing also decreased Type III cells more than a single dose, but loss of these cells may be due to factors related to the general health and/or cell renewal of taste buds rather than the life span of Type III cells. In general, pretreatment with amifostine appeared to protect taste cell renewal and the population of cells within taste buds from the cytotoxic effects of CYP with few observable adverse effects due to repeated administration. These findings may have important implications for patients undergoing chemotherapy.
Identifiants
pubmed: 30947285
doi: 10.1371/journal.pone.0214890
pii: PONE-D-19-03112
pmc: PMC6448888
doi:
Substances chimiques
Antineoplastic Agents
0
Protective Agents
0
Snap25 protein, mouse
0
Synaptosomal-Associated Protein 25
0
Cyclophosphamide
8N3DW7272P
Phospholipase C beta
EC 3.1.4.11
Plcb2 protein, mouse
EC 3.1.4.11
Amifostine
M487QF2F4V
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0214890Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC012829
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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