Quercetin Promotes Functional Recovery Following Acute Spinal Cord Injury

Abstract

We tested the hypothesis that quercetin, a potent Fe(2+)-chelating flavonoid, would decrease secondary damage following spinal cord trauma. MRI studies using the relaxation of the T1 proton signal caused by Fe(2+) ions and the dose-dependent reversal of this effect by addition of quercetin in aqueous solution were used to guide us to the dosage of quercetin to be used in animal experimentations. Forty-four male Wistar rats were used in two experimental series to test the hypothesis that administration of quercetin improves recovery of motor function after acute traumatic spinal cord injury. Animals were subjected to laminectomy and subjected to an extradural 40-g force clip compression for 5 sec at T7. Quercetin or saline was administered intraperitoneally 1 h after injury and then every 12 hr thereafter. Recovery of motor function was assessed using BBB scores at weekly intervals for 4 weeks. A dose of 2.5 micromoles quercetin/kg body weight did not result in significantly better functional outcome, whereas doses ranging from 5 to 100 micromoles quercetin/kg body weight resulted in a significantly better functional outcome with half or more of the animals walking, although with deficit; in contrast, no animals walked in the group of saline-treated animals. No significant differences in behavioral outcome were seen amongst the doses ranging from 5 to 100 micromol/kg, nor was there a difference if animals were treated for 4 or 10 days. Therapeutic outcome was coincident with more efficient iron clearance, suggesting that one possible mechanism whereby quercetin decreases secondary damage is through iron chelation.

Comparative effects of flavonoids on oxidant scavenging and ischemia-reperfusion injury in cardiomyocytes

“…With epidemiological evidence supporting that flavonoids reduce the risk of coronary artery disease (Hertog et al, 1993;Renaud and de Lorgeril, 1992), recent interest has been directed toward their therapeutic potential in the acute stages of the diseases (Rossi et al, 2003;Schultke et al, 2003). Our current study shows that five distinct flavonoids confer varied cardioprotection against ischemia/reperfusion injury, depending on the treatment timing.…”

Ceruloplasmin Protects Injured Spinal Cord from Iron-Mediated Oxidative Damage

“…These effects of the chelator in wild-type mice are likely independent of Cp. Previous work using iron chelators in spinal cord injury include studies on the polyphenolic compound quercetin, which also has antioxidant and other antiinflammatory effects (Schültke et al, 2003), and studies using a combination of an iron chelator and a mitotic inhibitor for fibroblast proliferation in a model of spinal cord hemisection to reduce the collagen scar induced by meningeal cells (Hermanns et al, 2001;Klapka et al, 2005). In contrast to these studies, our work addresses the issue of iron homeostasis and detoxification, which has not been addressed previously.…”

Tempol, a Nitroxide Antioxidant, Improves Locomotor and Histological Outcomes after Spinal Cord Contusion in Rats

“…Consistent with a role of glutathione synthesis, the cysteine prodrug, OTC, also increases pools of cysteine and glutathione and improves locomotor recovery and spares spinal cord tissue in spinal cord compression injury (Kamencic et al, 2001). Quercitin has similar effects on spinal compression injury and may act by chelating iron released by injury so that the generation of toxic levels of hydroxyl radicals by Haber Weiss/Fenton reactions from superoxide and hydrogen peroxide is inhibited (Schultke et al, 2003).…”

“…A variety of agents such as methylprednisolone (Behrmann et al, 1994;Hall, 2001), cycloheximide (Liu et al, 1997), L-2-oxothiazolidine-4-carboxylate (OTC; Kamencic et al, 2001), and quercitin (Schultke et al, 2003) have been used to oppose ROS-mediated neurodegeneration following spinal cord injury. In the case of methylprednisolone, the steroid has been thought to act as a free radical scavenger, since supraphysiological amounts are administered to achieve neuroprotection.…”