Effects of Recombinant Activated Protein C Derived From Drotrecogin-Alpha on Bleomycin-Induced Pulmonary Fibrosis in Rats Compared with Methyl-Prednisolone

OBJECTIVE: In this study, we aimed to test the preventive effects of intraperitoneally administered drotrecogin alpha which is derived from activated protein C (APC), on bleomycin-induced pulmonary fibrosis in rats, and to compare the effects of APC with the effects of methyl-prednisolone, a traditional therapy. MATERIAL AND METHODS: Thirty male Wistar albino rats were randomly allocated into four groups: 1. Saline alone (n=6); 2. Bleomycin+placebo (n=7); 3. Bleomycin+methyl-prednisolone (n=7); 4. Bleomycin+APC (n=10). The rats (except for the control group) were given intratracheal bleomycin (2.5 mg/kg). The bleomycin+APC group was given APC (100 μg/kg/day) and methyl-prednisolone treated rats were injected with 5mg/kg/day methyl-prednisolone intraperitoneally two days before the bleomycin injection; the drug was administered at the same dose for 16 days. All of the rats were killed 14 days after the intratracheal injection of bleomycin. Fibrotic changes in the lungs were demonstrated by analysing the cellular composition of bronchoalveolar lavage fluid, histological evaluation and lung hydroxyproline content.RESULTS: Fibrosis was experimentally induced in the lungs of rats using bleomycin. Fibrosis scores in the bleomycin+methyl-prednisolone and the bleomycin+APC groups were significantly lower than in the bleomycin+placebo group (p<0.05). The scores of the bleomycin+APC group and the bleomycin+methyl-prednisolone group were similar. The lung tissue hydroxyproline contents in the bleomycin+placebo and bleomycin+methyl-prednisolone groups were significantly higher than the control group (p<0.05), but the hydroxyproline content in the bleomycin+APC group was significantly lower than in the other groups (p<0.05). CONCLUSION: Drotrecogin alpha that is derived from recombinant APC has a protective effect on the pulmonary fibrosis induced by bleomycin. The protective effect seen with methyl-prednisolone is similar.