Ovariectomy aggravates hypersensitivity reactions to paclitaxel in rats

Takeshi Goromaru, Yoshinori Itoh, Toshiaki Sendo, Kenji Kobayashi, Takahisa Yano, Hiroaki Ikesue, Ryozo Oishi

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Abstract

The incidence of hypersensitivity reactions is still a matter of serious concern during chemotherapy with paclitaxel, particularly in patients with ovarian cancer. We recently reported that intravenous injection of paclitaxel causes acute lung injury characterized by vascular hyperpermeability, edema and respiratory dysfunction in rats. In the present study, we investigated the influence of ovariectomy on the paclitaxel-induced acute lung injury in rats. Ovariectomy worsened paclitaxel-induced acute lung injury, which was reversed by 17β-estradiol. The mRNA expression for endothelial nitric oxide synthase was reduced in lungs of ovariectomized rats. To determine the role for nitric oxide, we examined the effects of several agents that modulate nitric oxide concentration on the pulmonary response to paclitaxel. In ovary-intact rats, a nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester exaggerated paclitaxel-induced acute lung injury, while nitric oxide donors such as sodium nitroprusside and isosorbide dinitrate attenuated the lung injury. Sodium nitroprusside was also effective in alleviating the paclitaxel-induced acute lung injury in ovariectomized rats. These findings suggest that ovariectomy enhances the susceptibility to paclitaxel hypersensitivity, in which decrease in estrogen and subsequent reduction in nitric oxide synthesis may be involved.

Original languageEnglish
Pages (from-to)225-230
Number of pages6
JournalCancer Biology and Therapy
Volume4
Issue number2
Publication statusPublished - Feb 2005
Externally publishedYes

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Keywords

  • Estrogen
  • Hypersensitivity
  • Nitric oxide
  • Ovariectomy
  • Paclitaxel
  • Pulmonary edema
  • Vascular permeability

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Goromaru, T., Itoh, Y., Sendo, T., Kobayashi, K., Yano, T., Ikesue, H., & Oishi, R. (2005). Ovariectomy aggravates hypersensitivity reactions to paclitaxel in rats. Cancer Biology and Therapy, 4(2), 225-230.