PURPOSE: The enzymes COX-2 and CYT-c are well known to be an important part of the complicated fibrotic pathway.EPO is a multiple functional cytokine with anti-inflammatory,anti-apoptotic and antioxidative properties.Aim of this study was to investigate whether EPO plays or not a role in the expression of both enzymes in BLM- induced PF in rats.
METHODS: Fifty Wistar rats (300gr) were divided into five groups. Group 1 (n=10): control animals, Group 2 (n=10): the animals underwent intratracheal (i.t) and intraperitoneal (i.p) injection of saline (0.5ml/kg), Group 3 (n=10): the animals underwent BLM hydrochloride (7.5mg/kg) i.t injection, Group 4 (n=10): the animals underwent BLM hydrochloride (7.5mg/kg) i.t injection followed by EPO i.p injection (2000 iu/kg),Group 5 (n=10): the animals underwent 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 the group of animals which received only BLM (group 3)and in the lower grades for the group of animals which received BLM+EPO (group4) (p<0.001 and p<0.05 respectively).
CONCLUSIONS: BLM injection followed by EPO resulted in significant lower expression of COX-2 and CYT-c compared with the group of animals which was administrated only with BLM.
CLINICAL IMPLICATIONS: The protective mechanisms of EPO on PF must be further investigated in order to clarify as much as possible the role of this cytokine in the treatment of this lethal disease.
DISCLOSURE: The following authors have nothing to disclose: Drosos Tsavlis, Anna Tzoumaka, Georgia Kokaraki, Kokona Kouzi-Koliakos, Anastasia Tektonidou, Ioannis Angomachalelis, Dimitrios Koutsonikolas, Evangelia Spandou
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