Anti-inflammatory drugs ameliorate opposite enzymatic changes in ileal 5-hydroxytryptamine metabolism in the delayed phase after cisplatin administration to rats

被引：20

作者：

Ju, Chuanxia ^{[1
,2
]}

Hamaue, Naoya ^{[1
]}

Machida, Takuji ^{[1
]}

Liu, Yanxia ^{[1
]}

Iizuka, Kenji ^{[1
]}

Wang, Yue ^{[2
]}

Minami, Masaru ^{[3
]}

Hirafuji, Masahiko ^{[1
]}

机构：

[1] Hlth Sci Univ Hokkaido, Fac Pharmaceut Sci, Dept Pharmacol Sci, Ishikari, Hokkaido 0610293, Japan

[2] Qingdao Univ, Coll Med, Dept Pharmacol, Qingdao 266021, Shandong, Peoples R China

[3] Touei Hosp, Gerontol Unit Oozora, Sapporo, Hokkaido 0070880, Japan

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2008年 / 589卷 / 1-3期

关键词：

cisplatin; 5-hydroxytryptamine (5-HT); tryptophan hydroxylase; monoamine oxidase; cyclooxygenase-2; anti-inflammatory drugs;

D O I：

10.1016/j.ejphar.2008.04.050

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The effects of anti-inflammatory drugs on ileal 5-hydroxytryptamine (5-HT) metabolic dynamics at 72 h after a single administration of cisplatin were investigated in rats. Cisplatin 5 mg/kg i.p. caused pathological changes, with an inflammatory response occurring 72 h after its administration. The inflammatory response was associated with the induction of cyclooxygenase-2, but not cyclooxygenase-1, in the ileal mucosa at 72 h after the cisplatin administration. Daily treatment with meloxicam 3 mg/kg s.c. ameliorated the cisplatin-induced mucosal damage, whereas dexamethasone I mg/kg s.c. did not. Cisplatin administration also caused a significant increase in cyclooxygenase-2 mRNA expression at 72 h after administration, which was blunted by dexamethasone, but not by meloxicam. Cisplatin increased the content of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), but had no effect on 5-HT turnover (5-HIAA/5-HT ratio). Meloxicam and dexamethasone did not significantly decrease 5-HT and 5-HIAA content. Cisplatin significantly decreased monoamine oxidase activity but increased tryptophan hydroxylase (TPH) activity and TPH1 mRNA expression in ileal tissue. Meloxicam and dexamethasone significantly restored the decreased monoamine oxidase activity and inhibited the cisplatin-induced increase in tryptophan hydroxylase activity toward the control levels. These drugs also decreased the cisplatin-induced increase in TPH1 mRNA expression. Neither cisplatin nor the anti-inflammatory drugs had significant effect on mRNA expression of the serotonin re-uptake transporter. These results suggest that the inflammatory response associated with cyclooxygenase-2 induction is involved in the opposite change in ileal tryptophan hydroxylase and monoamine oxidase activities in the delayed phase after single administration of cisplatin to rats. (c) 2008 Elsevier B.V. All rights reserved.

引用

页码：281 / 287

页数：7

共 39 条

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