Similarity and difference in the acute lung injury induced by a radiographic contrast medium and an anticancer agent paclitaxel in rats

• Published in: Toxicology letters Vol. 152; no. 1; pp. 27 - 34
• Main Authors: Itoh, Yoshinori, Sendo, Toshiaki, Hirakawa, Toshio, Goromaru, Takeshi, Sakai, Naoko, Nakano, Hitoo, Oishi, Ryozo
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 30.08.2004; Amsterdam Elsevier Science
• Subjects: Acute lung injury; Animals; Antineoplastic Agents, Phytogenic - adverse effects; Biological and medical sciences; Contrast Media - adverse effects; Diagnosis, Differential; Drug Hypersensitivity - physiopathology; Drug Hypersensitivity - prevention & control; Drug toxicity and drugs side effects treatment; Dyspnea - chemically induced; Histamine; Histamine - pharmacology; Ioxaglic Acid - adverse effects; Lung - drug effects; Lung - pathology; Male; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Paclitaxel; Paclitaxel - adverse effects; Pharmacology. Drug treatments; Pulmonary Edema - chemically induced; Radiocontrast medium; Rat; Rats; Rats, Sprague-Dawley; Substance P; Substance P - pharmacology; Acute lung injury; Histamine; Rat; Substance P; Radiocontrast medium; Paclitaxel; Antineoplastic agent; Terpenoid; Peptides; Similarity; Acute; Lung; Rodentia; Peptide hormone; Respiratory system; Neuropeptide; Vertebrata; Mammalia; Taxane derivatives; Animal; Diterpene; Neurotransmitter; Antimitotic
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2004.03.022

Paclitaxel is one of the most frequently used anticancer agents but its use is sometimes limited because of the incidence of severe hypersensitivity reactions. The clinical symptoms of the reactions, including dyspnea and pulmonary edema, are similar to those induced by iodinated contrast medium during radiographic examination. Therefore, the premedication for the prophylaxis of hypersensitivity reactions to paclitaxel is carried out in accordance with that for radiographic contrast medium. In the present study, we compared the effects of paclitaxel and an iodinated radiocontrast medium ioxaglate on vascular permeability and pulmonary function in rats. Both paclitaxel (15 mg/kg) and ioxaglate (4 g iodine/kg) caused perivascular edema, plasma extravasation and decrease in arterial PaO 2. Dexamethasone inhibited plasma extravasation induced by the two compounds. In contrast, histamine H 1 and H 2 antagonists attenuated the effects of ioxaglate without inhibiting those of paclitaxel. On the other hand, a neurokinin NK 1 antagonist (LY303870: 0.5 mg/kg) significantly inhibited the pulmonary responses induced by paclitaxel but not by ioxaglate. Therefore, it is suggested that paclitaxel and ioxaglate cause similar acute lung injury but the mechanisms are different between the two compounds, in which histamine and substance P are involved in the pulmonary dysfunction induced by ioxaglate and paclitaxel, respectively. These findings also raise a possibility that more effective premedication is required for the prophylaxis of paclitaxel hypersensitivity.