Similarity and difference in the acute lung injury induced by a radiographic contrast medium and an anticancer agent paclitaxel in rats.
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 PaO2. Dexamethasone inhibited plasma extravasation induced by the two compounds. In contrast, histamine H1 and H2 antagonists attenuated the effects of ioxaglate without inhibiting those of paclitaxel. On the other hand, a neurokinin NK1 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.
Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. yositou@st.hosp.kyushu-u.ac.jp
Yoshinori
Y
Itoh
Toshiaki
T
Sendo
Toshio
T
Hirakawa
Takeshi
T
Goromaru
Naoko
N
Sakai
Hitoo
H
Nakano
Ryozo
R
Oishi
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D003287:Contrast Media / Q000009:adverse effects*; D003937:Diagnosis, Differential; D004342:Drug Hypersensitivity / Q000503:physiopathology* / Q000517:prevention & control*; D004417:Dyspnea / Q000139:chemically induced; D006632:Histamine / Q000494:pharmacology*; D007485:Ioxaglic Acid / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D017239:Paclitaxel / Q000009:adverse effects*; D011654:Pulmonary Edema / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D003287:Contrast Media; D013373:Substance P; D006632:Histamine; D017239:Paclitaxel; D007485:Ioxaglic Acid