Pemirolast reduces cisplatin-induced kaolin intake in rats

Yoko Tatsushima, Nobuaki Egashira, Naohiro Matsushita, Kentaro Kurobe, Takehiro Kawashiri, Takahisa Yano, Ryozo Oishi

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Emesis is the most feared side effect in patients who are undergoing cancer chemotherapy. In particular, cisplatin causes severe acute and delayed emesis. Although early vomiting is well controlled by 5-hydroxytryptamine 3 (5-HT 3) receptor antagonists, delayed-phase vomiting is not sufficiently controlled. Substance P is thought to be involved in the development of emesis, and tachykinin NK1 receptor antagonists can inhibit delayed vomiting. We previously have reported that substance P is involved in the paclitaxel-induced hypersensitivity reaction in rats, and anti-allergic agent pemirolast reduces these reactions via inhibition of substance P release. In the present study, we investigated the effect of pemirolast on cisplatin-induced kaolin intake, which is an index of nausea/vomiting in the rat. Cisplatin (5 mg/kg, i.p.) induced kaolin intake and reduced normal feed intake from days 1 to 5 after injection. Cisplatin-induced kaolin intake was significantly reduced by co-administration of ondansetron (2 mg/kg, i.p.), a 5-HT3 receptor antagonist, and dexamethasone (2 mg/kg, i.p.) from days 1 to 5. Similarly, pemirolast (10 mg/kg, p.o.) and the tachykinin NK1 receptor antagonist aprepitant (10 and 30 mg/kg, p.o.) significantly reduced cisplatin-induced kaolin intake on days 3 and 4. Moreover, pemirolast at the same dose significantly reversed the cisplatin-induced increase in the cerebrospinal fluid level of substance P in rats. These results suggest that substance P is involved in cisplatin-induced kaolin intake in rats, and pemirolast reduces kaolin intake by inhibition of substance P release.

Original languageEnglish
Pages (from-to)57-62
Number of pages6
JournalEuropean Journal of Pharmacology
Volume661
Issue number1-3
DOIs
Publication statusPublished - Jul 1 2011

Fingerprint

pemirolast
Kaolin
Cisplatin
Vomiting
Substance P
Tachykinin Receptors
Receptors, Serotonin, 5-HT3
aprepitant
Serotonin 5-HT3 Receptor Antagonists
Ondansetron
Anti-Allergic Agents
Paclitaxel
Nausea
Dexamethasone
Cerebrospinal Fluid

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Pemirolast reduces cisplatin-induced kaolin intake in rats. / Tatsushima, Yoko; Egashira, Nobuaki; Matsushita, Naohiro; Kurobe, Kentaro; Kawashiri, Takehiro; Yano, Takahisa; Oishi, Ryozo.

In: European Journal of Pharmacology, Vol. 661, No. 1-3, 01.07.2011, p. 57-62.

Research output: Contribution to journalArticle

Tatsushima, Yoko ; Egashira, Nobuaki ; Matsushita, Naohiro ; Kurobe, Kentaro ; Kawashiri, Takehiro ; Yano, Takahisa ; Oishi, Ryozo. / Pemirolast reduces cisplatin-induced kaolin intake in rats. In: European Journal of Pharmacology. 2011 ; Vol. 661, No. 1-3. pp. 57-62.
@article{73aaea03534640ef8d6a76798d490be7,
title = "Pemirolast reduces cisplatin-induced kaolin intake in rats",
abstract = "Emesis is the most feared side effect in patients who are undergoing cancer chemotherapy. In particular, cisplatin causes severe acute and delayed emesis. Although early vomiting is well controlled by 5-hydroxytryptamine 3 (5-HT 3) receptor antagonists, delayed-phase vomiting is not sufficiently controlled. Substance P is thought to be involved in the development of emesis, and tachykinin NK1 receptor antagonists can inhibit delayed vomiting. We previously have reported that substance P is involved in the paclitaxel-induced hypersensitivity reaction in rats, and anti-allergic agent pemirolast reduces these reactions via inhibition of substance P release. In the present study, we investigated the effect of pemirolast on cisplatin-induced kaolin intake, which is an index of nausea/vomiting in the rat. Cisplatin (5 mg/kg, i.p.) induced kaolin intake and reduced normal feed intake from days 1 to 5 after injection. Cisplatin-induced kaolin intake was significantly reduced by co-administration of ondansetron (2 mg/kg, i.p.), a 5-HT3 receptor antagonist, and dexamethasone (2 mg/kg, i.p.) from days 1 to 5. Similarly, pemirolast (10 mg/kg, p.o.) and the tachykinin NK1 receptor antagonist aprepitant (10 and 30 mg/kg, p.o.) significantly reduced cisplatin-induced kaolin intake on days 3 and 4. Moreover, pemirolast at the same dose significantly reversed the cisplatin-induced increase in the cerebrospinal fluid level of substance P in rats. These results suggest that substance P is involved in cisplatin-induced kaolin intake in rats, and pemirolast reduces kaolin intake by inhibition of substance P release.",
author = "Yoko Tatsushima and Nobuaki Egashira and Naohiro Matsushita and Kentaro Kurobe and Takehiro Kawashiri and Takahisa Yano and Ryozo Oishi",
year = "2011",
month = "7",
day = "1",
doi = "10.1016/j.ejphar.2011.04.026",
language = "English",
volume = "661",
pages = "57--62",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1-3",

}

TY - JOUR

T1 - Pemirolast reduces cisplatin-induced kaolin intake in rats

AU - Tatsushima, Yoko

AU - Egashira, Nobuaki

AU - Matsushita, Naohiro

AU - Kurobe, Kentaro

AU - Kawashiri, Takehiro

AU - Yano, Takahisa

AU - Oishi, Ryozo

PY - 2011/7/1

Y1 - 2011/7/1

N2 - Emesis is the most feared side effect in patients who are undergoing cancer chemotherapy. In particular, cisplatin causes severe acute and delayed emesis. Although early vomiting is well controlled by 5-hydroxytryptamine 3 (5-HT 3) receptor antagonists, delayed-phase vomiting is not sufficiently controlled. Substance P is thought to be involved in the development of emesis, and tachykinin NK1 receptor antagonists can inhibit delayed vomiting. We previously have reported that substance P is involved in the paclitaxel-induced hypersensitivity reaction in rats, and anti-allergic agent pemirolast reduces these reactions via inhibition of substance P release. In the present study, we investigated the effect of pemirolast on cisplatin-induced kaolin intake, which is an index of nausea/vomiting in the rat. Cisplatin (5 mg/kg, i.p.) induced kaolin intake and reduced normal feed intake from days 1 to 5 after injection. Cisplatin-induced kaolin intake was significantly reduced by co-administration of ondansetron (2 mg/kg, i.p.), a 5-HT3 receptor antagonist, and dexamethasone (2 mg/kg, i.p.) from days 1 to 5. Similarly, pemirolast (10 mg/kg, p.o.) and the tachykinin NK1 receptor antagonist aprepitant (10 and 30 mg/kg, p.o.) significantly reduced cisplatin-induced kaolin intake on days 3 and 4. Moreover, pemirolast at the same dose significantly reversed the cisplatin-induced increase in the cerebrospinal fluid level of substance P in rats. These results suggest that substance P is involved in cisplatin-induced kaolin intake in rats, and pemirolast reduces kaolin intake by inhibition of substance P release.

AB - Emesis is the most feared side effect in patients who are undergoing cancer chemotherapy. In particular, cisplatin causes severe acute and delayed emesis. Although early vomiting is well controlled by 5-hydroxytryptamine 3 (5-HT 3) receptor antagonists, delayed-phase vomiting is not sufficiently controlled. Substance P is thought to be involved in the development of emesis, and tachykinin NK1 receptor antagonists can inhibit delayed vomiting. We previously have reported that substance P is involved in the paclitaxel-induced hypersensitivity reaction in rats, and anti-allergic agent pemirolast reduces these reactions via inhibition of substance P release. In the present study, we investigated the effect of pemirolast on cisplatin-induced kaolin intake, which is an index of nausea/vomiting in the rat. Cisplatin (5 mg/kg, i.p.) induced kaolin intake and reduced normal feed intake from days 1 to 5 after injection. Cisplatin-induced kaolin intake was significantly reduced by co-administration of ondansetron (2 mg/kg, i.p.), a 5-HT3 receptor antagonist, and dexamethasone (2 mg/kg, i.p.) from days 1 to 5. Similarly, pemirolast (10 mg/kg, p.o.) and the tachykinin NK1 receptor antagonist aprepitant (10 and 30 mg/kg, p.o.) significantly reduced cisplatin-induced kaolin intake on days 3 and 4. Moreover, pemirolast at the same dose significantly reversed the cisplatin-induced increase in the cerebrospinal fluid level of substance P in rats. These results suggest that substance P is involved in cisplatin-induced kaolin intake in rats, and pemirolast reduces kaolin intake by inhibition of substance P release.

UR - http://www.scopus.com/inward/record.url?scp=79956222398&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79956222398&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2011.04.026

DO - 10.1016/j.ejphar.2011.04.026

M3 - Article

C2 - 21539837

AN - SCOPUS:79956222398

VL - 661

SP - 57

EP - 62

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-3

ER -