The effect of erythropoietin (EPO) on cyclooxygenase-2 (COX-2) and cytochrome-c (CYT-c) in the bleomycin (BLM)-induced pulmonary fibrosis (PF) in rats

Purpose: The enzymes COX-2 and CYT-c are known to be a part of the fibrotic pathway.EPO is a multiple functional cytokine with anti-inflammatory and anti-apoptotic properties. Aim of this study was to investigate the role of EPO on the expression of both enzymes in BLM- induced PF in rats. Methods: Fifty Wistar rats (300gr) were divided into five groups of 10 animals each:1)control animals,2)intratracheal (i.t) and intraperitoneal (i.p) injection of saline (0.5ml/kg),3)BLM hydrochloride (7.5mg/kg) i.t injection,4)BLM hydrochloride (7.5mg/kg) i.t injection followed by EPO i.p injection (2000 iu/kg),5)saline (0.5ml/kg) i.t injection followed by EPO i.p injection (2000 iu/kg). All rats were sacrified after 14 days.Immunohistochemical evaluation was performed for the expression of COX-2 and Cyt-c.A scale of 4 grades was used for the evaluation of the results: 0-25% (A),25-50% (B),50-75% (C),75-100% (D). Results: In groups 1,2 and 5, both COX-2 and CYT-c were expressed in the grade A (80%) and in the grade B (20%). In group 3,COX-2 was expressed in the high grades B (20%),C (60%) and D (20%),and CYT-c only in the two higher grades C (70%) and D (30%). In group 4,both enzymes were expressed only in the low grades A (80% and 70% respectively) and B (20% and 30% respectively). The expression of COX-2 and CYT-c took place in the high grades for BLM group and in the lower grades for BLM+EPO group (p Conclusions: BLM injection followed by EPO resulted in significant lower expression of COX-2 and CYT-c compared with BLM group. The protective mechanisms of EPO on PF must be further clarified.