The long-term evaluation of pulmonary toxicity following isolated lung perfusion with melphalan in the rat.
The present study was conducted to evaluate the long-term pulmonary toxicity of isolated lung perfusion (ILP) with melphalan in the rat model. F344 rats were treated by ILP with 1 mg of melphalan or buffered hespan (BHE). The rats in the melphalan group were sacrificed randomly 30, 60, 90, 120, 150, and 180 days after the perfusion. Pulmonary toxicity was evaluated by pathological analysis. In the melphalan group, light and electron microscopic findings revealed perivascular and peribronchial edema, and septal thickening with cellular infiltration of the interstitial space 30 days after the perfusion, but all of these changes had disappeared by 60 days. Azan stain showed a slight increase of the connective tissue at the alveolar wall in the melphalan group, but no progressive pulmonary interstitial fibrosis was observed after 180 days. Transmission electron microscopy showed minimal proliferation of the type II pneumocytes of normal appearance in the melphalan group. In conclusion, the long-term pulmonary toxicity of ILP with melphalan is acceptable; however clinical trials of this therapy need to be conducted.
Ueda
K
K
First Department of Surgery, Yamaguchi University School of Medicine, Japan.
Sugi
K
K
Li
T S
TS
Saeki
K
K
Nawata
S
S
Esato
K
K
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008558:Melphalan / Q000633:toxicity*; D010477:Perfusion; D051381:Rats; D011916:Rats, Inbred F344
D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan