Antioxidant and antiapoptotic effects of darbepoetin-α against traumatic brain injury in rats
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Submission date: 2013-07-22
Final revision date: 2013-08-30
Acceptance date: 2013-10-04
Online publication date: 2015-10-12
Publication date: 2015-10-31
Arch Med Sci 2015;11(5):1119–1128
Introduction: In this study, we tried to determine whether darbepoetin-α 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 α), 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-α 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-α 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-α 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 α significantly reduced the malondialdehyde levels (p < 0.001). Due to the elevated apoptotic activity following the injury, caspase-3 activity increased significantly. Darbepoetin-α 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-α was shown to be at least as effective as methylprednisolone in protecting brain from oxidative stress, lipid peroxidation and apoptosis.