Effect of paraquat on plasma fibronectin, serum free hydroxyproline, serum ceruloplasmin and lung collagen content in monkeys.
The purpose of this study was to characterize paraquat toxicity in monkeys and to determine the feasibility of using the monkey as an animal model for the study of paraquat-induced pulmonary fibrosis in humans. Sixteen Japanese monkeys (Macaca fuscata), more than 3.5 years of age, with bodyweight ranging from 3.2 kg to 10.2 kg, were randomly divided into two groups. They were administered paraquat dichloride (PQ) by injection (s.c.) at a dose of 2.0 mg/kg bodyweight (12 monkeys) or s.c. saline, at a dose of 0.2 ml/kg bodyweight (control group, 4 monkeys), every two days for a period of four to five times. Eight monkeys (66.7%) from the PQ treatment groups expired due to subchronic PQ toxicity from days 11 to 35. Four monkeys (33.3%) from the PQ treatment group and all four monkeys from the control group survived the observation period of 66 days. On day 66, all of the surviving monkeys were sacrificed and examined for possible histopathological changes and the lung hydroxyproline content was determined. Our results indicate that the concentration of free hydroxyproline and plasma fibronectin did not vary significantly. The serum ceruloplasmin for the monkeys of the PQ treatment groups was significantly increased from day 14 to 21, compared to the control group. Also the total lung collagen of both the expired and surviving monkeys in the PQ treatment groups was elevated significantly, compared to the control group. The monkeys can provide extensive opportunities for research on the mechanism and the treatment of PQ poisoning in man.
Department of Pharmacology, School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
T
T
Masaoka
F
F
Akahori
S
S
Arai
K
K
Sakaguchi
D000818:Animals; D002570:Ceruloplasmin / Q000097:blood*; D003094:Collagen / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D006909:Hydroxyproline / Q000097:blood*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008251:Macaca; D008297:Male; D009391:Nephelometry and Turbidimetry; D010269:Paraquat / Q000633:toxicity*; D013056:Spectrophotometry, Ultraviolet
D005353:Fibronectins; D003094:Collagen; D002570:Ceruloplasmin; D010269:Paraquat; D006909:Hydroxyproline