A new antioxidant compound H-290/51 attenuates upregulation of constitutive isoform of heme oxygenase (HO-2) following trauma to the rat spinal cord.
Influence of a new antioxidant compound H-290/51 on carbon monoxide (CO) production following spinal cord injury was examined using immunohistochemistry of the constitutive isoform of heme oxygenase-2 (HO-2) in a rat model. Subjection of rats to 5 h spinal cord injury by making an incision into the right dorsal horn of the T10-11 segments resulted in upregulation of HO-2 in the injured and adjacent T9 and T12 segments. At this time, disruption of the blood-spinal cord barrier (BSCB) permeability, edema formation and cell injury were more pronounced. Pretreatment with H-290/51 (50 mg/kg, p.o., 30 min before trauma) significantly attenuated the HO-2 immunoreactivity along with breakdown of the BSCB permeability, edema and cell injury. These results for the first time demonstrate that the antioxidant compound H-290/51 is capable of attenuating HO-2 expression and thereby influencing CO production. Furthermore, our observations indicate that oxidative stress is involved in CO production, as reflected by HO-2 expression, which is injurious to the cord and H-290/51 exerts powerful neuroprotective effects in spinal cord injury.
Sharma
H S
HS
Laboratory of Neuroanatomy, Department of Medical Cell Biology, Biomedical Centre, Uppsala University, Uppsala, Sweden.
Alm
P
P
Sjöquist
P O
PO
Westman
J
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002248:Carbon Monoxide / Q000378:metabolism*; D004487:Edema / Q000473:pathology / Q000503:physiopathology*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000201:enzymology* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
D000975:Antioxidants; C088233:H290-51; D007211:Indoles; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2