Effects of the combined administration of vitamins C and E on the oxidative stress status and programmed cell death pathways after experimental spinal cord injury.

ABSTRACT

STUDY DESIGN: Experimental, controlled, animal study. OBJECTIVES: To assess the effects of vitamins C and E (VCE) treatment on oxidative stress and programmed cell deaths after rat spinal cord injury (SCI), as well as functional recovery. SETTING: Taiwan. METHODS: Fifty-four Sprague-Dawley rats were used for the experimental procedure. In the sham group, laminectomy at T10 was performed, followed by impactor contusion of the spinal cord. In the control group, only a laminectomy was performed without contusion. Oxidative stress status was assessed by measuring the spinal cord tissue content of superoxide dismutase (SOD) and gluthatione peroxidase (GSH-Px) activities. We also evaluated the effects of combined VCE treatment using western blot to analyze expression of cleaved caspase-3 and microtubule-associated protein light chain 3 (LC3), and the Basso, Beattie and Bresnahan (BBB) scale to evaluate functional outcomes. RESULTS: Combined treatment of VCE significantly counteracted the effects of spinal cord contusion on oxidative stress represented by activities of SOD and GSH-Px (P<0.05). The VCE treatment also significantly enhanced LC3-II expression and decreased cleaved caspase-3 compared with the sham (P<0.05). Furthermore, BBB scores significantly improved in the VCE-treated group compared with the sham group (on day 14 and 28 after SCI; P<0.05). CONCLUSIONS: The combined administration of VCE was clearly capable of modulating the antioxidant effects, and of reducing apoptosis and increasing autophagy at the lesion epicenter leading to an improved functional outcome. Use of such clinically ready drugs could help earlier clinical trials in selected cases of human SCIs.