Effect of dehydroproline as a collagen synthetic inhibitor in paraquat-induced pulmonary fibrosis in beagle dogs.
To investigate the effect of 3,4-DL-dehydroproline (DHP) on paraquat (PQ)-induced pulmonary fibrosis in beagle dogs, 25 beagles without distinction of sex were allocated at random into 2 groups; 17 dogs were PQ-dosed and 8 were saline-dosed. The 17 dogs were given 1 mg PQ/kg/d sc for 7-11 d; 14 of the 17 had decreased body weight on day 11 and were selected, 2 of which were determined at random and necropsied. The remaining 12 dogs were randomly divided into 2 groups of 6 dogs each (DHP-treated or saline-treated). They received either 25 mg DHP/kg/d sc or saline for 14 d and were sacrificed for measurement of lung lipid peroxide and lung hydroxyproline (Hyp) concentrations on day 25 or 180 after the PQ administrations started. Two of the 17 dogs (11.8%) given 1 mg PQ/kg/d sc died on days 9 and 11 of the administration. One dog (5.9%) had no signs of PQ toxicity including no decrease in body weight. The remaining 14 dogs (82.4%) had decreased body weight until day 11 of the PQ administrations. No significant differences in erythrocyte superoxide dismutase, blood catalase and serum-lipid peroxide occurred from the PQ dosing; however, lung lipid peroxide increased 4-fold. On day 180 the lung lipid peroxide of the PQ + saline treated group was still 4-times elevated, while the PQ + DHP treated group had about 1/2 that value. Lung Hyp concentrations in the PQ dosed dogs were significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Akahori
F
F
Department of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
Nagata
T
T
Masaoka
T
T
Okinaka
T
T
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000097:blood; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004285:Dogs; D005260:Female; D006909:Hydroxyproline / Q000032:analysis; D008054:Lipid Peroxides / Q000032:analysis; D008297:Male; D010269:Paraquat / Q000506:poisoning*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D013482:Superoxide Dismutase / Q000097:blood
D008054:Lipid Peroxides; C002195:3,4-dehydroproline; D003094:Collagen; D011392:Proline; D002374:Catalase; D013482:Superoxide Dismutase; D010269:Paraquat; D006909:Hydroxyproline