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 journalArticlepeer-review

16 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

All Science Journal Classification (ASJC) codes

  • Pharmacology

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