Antioxidant and antiapoptotic effects of darbepoetin-alpha against traumatic brain injury in rats

作者:Kertmen Hayri; Gurer Bora*; Yilmaz Erdal Resit; Kanat Mehmet Ali; Arikok Ata Turker; Erguder Berrin Imge; Hasturk Askin Esen; Ergil Julide; Sekerci Zeki
来源:Archives of Medical Science, 2015, 11(5): 1119-1128.
DOI:10.5114/aoms.2015.54869

摘要

Introduction: In this study, we tried to determine whether darbepoetin-alpha would protect the brain from oxidative stress and apoptosis in a rat traumatic brain injury model.
Material and methods: The animals were randomized into four groups; group 1 (sham), group 2 (trauma), group 3 (darbepoetin a), group 4 (methylprednisolone). In the sham group only the skin incision was performed. In all the other groups, a moderate traumatic brain injury modelwas applied.
Results: Following trauma both glutathione peroxidase, superoxide dismutase levels decreased (p < 0.001 for both); darbepoetin-a increased the activity of both antioxidant enzymes (p = 0.001 and p < 0.001 respectively). Trauma caused significant elevation in the nitric oxide synthetase and xanthine oxidase levels (p < 0.001 for both). Administration of darbepoetin-a significantly decreased the levels of nitric oxide synthetase and xanthine oxidase (p < 0.001 for both). Also, trauma caused significant elevation in the nitric oxide levels (p < 0.001); darbepoetin-a administration caused statistically significant reduction in the nitric oxide levels (p < 0.001). On the other hand, malondialdehyde levels were increased following trauma (p < 0.001), and darbepoetin a significantly reduced the malondialdehyde levels (p < 0.001). Due to the elevated apoptotic activity following the injury, caspase-3 activity increased significantly. Darbepoetin-a treatment significantly inhibited apoptosis by lowering the caspase-3 activity (p < 0.001). In the darbepoetin group, histopathological score was lower than the trauma group (p = 0.016).
Conclusions: In this study, darbepoetin-a was shown to be at least as effective as methylprednisolone in protecting brain from oxidative stress, lipid peroxidation and apoptosis.

  • 出版日期2015