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 (Po0.05). The VCE treatment also significantly enhanced LC3-II expression and decreased cleaved caspase-3 compared with the sham (Po0.05). Furthermore, BBB scores significantly improved in the VCE-treated group compared with the sham group (on day 14 and 28 after SCI; Po0.05). 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.

Effects of calcitriol on experimental spinal cord injury in rats

“…The levels of oxidative stress and apoptosis are believed to be two of the most important factors involved in post-traumatic degeneration due to destruction of the damaged spinal cord. 3 Therefore, decreasing oxidation stress injury and inhibition of apoptosis are key factors in the therapeutic schedule of SCI. Calcitriol, that is 1,25-dihydroxyvitamin D 3 , is the biologically active metabolite of vitamin D and the predominant Ca 2+ -regulatory steroid hormone, 14 which has a major role in osteoporosis.…”

“…2 Furthermore, oxidative stress and apoptosis were shown to be important factors precipitating posttraumatic degeneration due to secondary destruction of the damaged spinal cord. 3 Although the precise molecular pathway of secondary injury is still controversial, therapeutic strategies that inhibit or delay oxidative stress and apoptosis may contribute to SCI recovery.…”

“…Furthermore, recent evidence suggests that stimulation of autophagy after SCI contributes to nerve cell selfprotection and locomotive recovery. 7 Calcitriol (C 44 H 80 O 4 Si 2 , also known as 1,25-dihydroxyvitamin D 3 ), which has biological functions in bone and calcium metabolism, has a key role in osteoporosis. However, calcitriol has recently been shown to have a number of bioactivities.…”

High-dose ascorbic acid administration improves functional recovery in rats with spinal cord contusion injury

“…12 Therefore, AA has been used for the treatment of many diseases, such as cardiovascular, digestive, respiratory, musclar, immune dysfunction, urogenital and, importantly, neurological diseases. 10,20 In fact, the effect of normaldose AA on SCI was previously investigated, and demonstrated that AA can alleviate the histological features of tissue injury, although it did not show significant effect on the behavioral function of the injured animals. 9 The results suggest that AA has positive effects on SCI; however, its usage at a normal dose has only limited protective effects.…”

“…10,12,19 One of the vital functions of AA is to clear free radicals, therefore exerting protective effect in various injuries. 12 Therefore, AA has been used for the treatment of many diseases, such as cardiovascular, digestive, respiratory, musclar, immune dysfunction, urogenital and, importantly, neurological diseases.…”