Neuroprotective effects of alpha-lipoic acid in experimental spinal cord injury in rats.
BACKGROUND
Oxidative stress is a mediator of secondary injury to the spinal cord following trauma.


OBJECTIVE
To investigate the putative neuroprotective effect of alpha-lipoic acid (LA), a powerful antioxidant, in a rat model of spinal cord injury (SCI).


METHODS
Wistar albino rats were divided as control, vehicle-treated SCI, and LA-treated SCI groups. To induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10 was used. Injured animals were given either 50 mg/kg LA or saline at 30 minutes postinjury by intraperitoneal injection. At 7 days postinjury, neurologic examination was performed, and rats were decapitated. Spinal cord samples were taken for histologic examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and DNA fragmentation. Formation of reactive oxygen species in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique.


RESULTS
SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in luminol CL and MDA levels, MPO activity, and DNA damage. Furthermore, LA treatment reversed all these biochemical parameters as well as SCI-induced histopathologic alterations. Conversely, impairment of the neurologic function caused by SCI remained unchanged.


CONCLUSIONS
The present study suggests that LA reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, glutathione depletion, and DNA fragmentation.
Marmara University School of Pharmacy, Department of Pharmacology, Istanbul, Turkey. haletoklu@yahoo.com
Hale Z
HZ
Toklu
Tayfun
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Hakan
Hasan
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Celik
Necat
N
Biber
Can
C
Erzik
Ayliz V
AV
Ogunc
Dilek
D
Akakin
Esra
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Cikler
Sule
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Cetinel
Mehmet
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Ersahin
Goksel
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Sener
D000704:Analysis of Variance; D000818:Animals; D053938:DNA Fragmentation / Q000187:drug effects*; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use*
D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D008063:Thioctic Acid; D009195:Peroxidase; D005978:Glutathione