Peplomycin sulfate and pulmonary fibrosis: hydroxyproline, uronic acid, proline hydroxylase and glucosamine 6-phosphate synthetase in lungs of hamsters treated with peplomycin.
Effect of peplomycin sulfate (PLM) on pulmonary fibrosis was examined. Hydroxyproline, uronic acid, proline hydroxylase (EC 1.14.11.2) and glucosamine 6-phosphate synthetase (EC 2.6.1.16) in lungs of hamsters treated with PLM were studied and compared with those of hamsters treated with bleomycin (BLM). PLM, when administered intraperitoneally, one injection daily for 10 consecutive days, at either a high- (5 mg/kg) or low- (2.8 mg/kg) dosage-level, caused no significant increase of lung hydroxyproline and uronic acid as compared with controls. BLM on the other hand effected a significant increase in lung hydroxyproline on the high-dosage level (5 mg/kg) but not on the low-dosage level (2.8 mg/kg). In contrast, when administering PLM intratracheally, the concentrations of hydroxyproline in lungs increased 20% over the control levels. A transient increase of proline hydroxylase and glucosamine 6-phosphate synthetase also occurred shortly after the instillation. These increases were also observed in the corresponding groups treated with BLM, which confirmed the previous observations by other investigators. However, the magnitude of the increase was relatively lower in those values of PLM as compared with those of BLM. These data suggested that (1) PLM, when administered with multiple dosages intraperitoneally, showed no significant effect on the elevation of lung hydroxyproline; (2) PLM, when administered with a dose intratracheally, induced pulmonary fibrosis similar to that caused by BLM. However, the hydroxyproline accumulation in lungs of PLM-treated hamsters was less than in those of the BLM-treated; (3) The fibrotic effect on the lungs caused by either PLM or BLM was probably attributed to acceleration of the syntheses of collagen and acidic glycosaminoglycans.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D002238:Carbohydrate Epimerases / Q000378:metabolism*; D006224:Cricetinae; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000378:metabolism*; D006909:Hydroxyproline / Q000032:analysis*; D007700:Kinetics; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008647:Mesocricetus; D017663:Peplomycin; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000503:physiopathology; D013329:Structure-Activity Relationship; D013997:Time Factors; D014574:Uronic Acids / Q000032:analysis*
D000900:Anti-Bacterial Agents; D014574:Uronic Acids; D001761:Bleomycin; D017663:Peplomycin; D011393:Procollagen-Proline Dioxygenase; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); D002238:Carbohydrate Epimerases; D006909:Hydroxyproline