Inhibitory effects of subcutaneous dexamethasone treatment on rat pulmonary toxicity of KW-2149, a new mitomycin C analogue.
An experimental model for pulmonary toxicity of KW-2149, a new mitomycin C analogue, was established and the inhibitory effects of dexamethasone (DM) were investigated. KW-2149 was given to male rats 3 or 5 times at weekly intervals by intravenous injection of 3.28 or 8.2 mg/kg. As a suitable model for pulmonary toxicity, the dose of 3.28 mg/kg per week for 3 weeks was selected, this causing exudative pleural effusion in all animals but no deaths. For preventing this toxicity, DM was injected subcutaneously 3 times every week at 0.5, 1.0, 2.5 or 5.0 mg/kg. The 0.5 mg/kg dose was sufficient to completely prevent development of pleural effusions. Combined DM treatment may be an effective chemotherapy for KW-2149 induced pulmonary toxicity.
Takaba
K
K
Toxicological Research Laboratories, Kyowa Hakko Kogyo Co. Ltd, Ube, Yamaguchi, Japan. katsumi.takaba@kyowa.co.jp
Furumoto
H
H
Ikegami
J
J
Suzuki
K
K
Takahashi
J
J
Hara
T
T
Ishii
A
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001485:Basement Membrane / Q000187:drug effects / Q000648:ultrastructure; D001835:Body Weight / Q000187:drug effects; D019963:Clinical Chemistry Tests; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004347:Drug Interactions; D004417:Dyspnea / Q000139:chemically induced / Q000188:drug therapy; D004727:Endothelium / Q000187:drug effects / Q000648:ultrastructure; D005938:Glucocorticoids / Q000627:therapeutic use*; D006403:Hematologic Tests; D007279:Injections, Subcutaneous; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008937:Mitomycins / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010996:Pleural Effusion / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000903:Antibiotics, Antineoplastic; D005938:Glucocorticoids; D008937:Mitomycins; C057625:KW 2149; D003907:Dexamethasone