Tempol reduces injury area in rat model of spinal cord contusion injury through suppression of iNOS and COX-2 expression.
The present study focused on the biologic effects of tempol on anti-inflammatory and nitric oxide generation in contusion spinal cord injury (SCI). The animal model of SCI was induced by dropping a 10-g rod (2.0 mm in diameter) at a height of 25 mm. Tempol was injected intraperitoneally a dose of 100 mg/kg at 15 min before SCI. Controls was injected with saline. The contused spinal segments were removed according to time courses, and the expression level of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was analyzed along with the size of irreversibly damaged region. After SCI, the relative amounts of COX-2 and iNOS mRNA were peaked at 8 h after post-injury, and then decreased up to 7 days post-injury, and normal level at 14 days. Expression of COX-2 protein was peaked at 8 h post-injury. With the tempol pre-treatment, the immunoreactivity of COX-2 and nitrotyrosine in paraffin-embedded tissue slices was profoundly decreased. The irreversibly damaged area of the spinal cord was peaked at 3 days after SCI. With tempol pre-treatment, the irreversibly damaged area shows a statistically significant decrease at 3 days after SCI. These evidences indicate that tempol pre-treatment reduces irreversibly damaged area on the contusion SCI in rat. The mechanisms of biologic reactions of tempol might be related to the decreased expressions of COX-2 and iNOS in spinal cord cells, neurons and glia. It is expected that the tempol effect on the SCI is not only antioxidant activity but also anti-inflammatory reaction.
College of Environmental Science and Engineering, Yangzhou University, Yangzhou, 225127, China, hhquan@yzu.edu.cn.
Hong-Hua
HH
Quan
Ku-Seong
KS
Kang
Yoon-Kyung
YK
Sohn
Ming
M
Li
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D004195:Disease Models, Animal; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013113:Spin Labels; D013119:Spinal Cord Injuries / Q000201:enzymology* / Q000473:pathology
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D003497:Cyclic N-Oxides; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013113:Spin Labels; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C001803:tempol