The antioxidant effects of melatonin in surgical brain injury in rats.
BACKGROUND
Surgical brain injury (SBI) to normal brain tissue can occur as inevitable sequelae of neurosurgical operations. SBI can contribute to post-operative complications such as brain edema following blood-brain barrier (BBB) disruption leading to neurological deficits. Melatonin is a commonly used drug with known antioxidant properties and neuroprotective effects in experimental animal studies (Chen et al., J Pineal Res 41:175-182, 2006; Chen et al., J Pineal Res 40(3):242-250, 2006; Cheung, J Pineal Res 34:153-160, 2003; Lee et al., J Pineal Res 42(3):297-309, 2007; Reiter et al., Exp Biol Med (Maywood) 230(2):104-117, 2005).


METHODS
We tested different concentrations of melatonin (5 mg/kg, 15 mg/kg and 150 mg/kg) administered 1 hour before surgery for neuroprotection against SBI using a rodent model. Post-operative assessment included brain water content (brain edema), lipid peroxidation assays (oxidative stress), and neurological assessment.


RESULTS
The results showed a trend in decreasing brain edema with lower doses of melatonin (5 mg/kg and 15 mg/ kg), however, high concentration of melatonin (150 mg/kg) significantly increased brain edema compared to all other groups. This deleterious effect of high-dose melatonin was also observed in lipid-peroxidation assay wherein lower-dose melatonin (15 mg/kg) attenuated oxidative stress, but high-dose melatonin (150 mg/kg) increased oxidative stress as compared to vehicle-treated group. Furthermore, high-dose melatonin also worsened neurological outcomes compared to other groups whereas; the low-dose melatonin group (15 mg/kg) showed some improved neurological parameters.


CONCLUSIONS
The study suggests that low-dose melatonin may provide neuroprotective effects against SBI. Further studies are needed to confirm this. More importantly, the findings of the study stress the need to carefully reassess safety issues with high doses of melatonin, which is considered to be a practically non-toxic drug.
Lee
Steve
S
Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, CA, USA. steveparklee@yahoo.com
Jadhav
Vikram
V
Ayer
Robert
R
Rojas
Hugo
H
Hyong
Amy
A
Lekic
Tim
T
Stier
Gary
G
Martin
Robert
R
Zhang
John H
JH
D000704:Analysis of Variance; D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D001930:Brain Injuries / Q000150:complications / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015227:Lipid Peroxidation / Q000187:drug effects; D008550:Melatonin / Q000627:therapeutic use*; D009460:Neurologic Examination / Q000379:methods; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats
D018696:Neuroprotective Agents; D008550:Melatonin