Zinc protoporphyrin aggravates cerebral ischemic injury following experimental subarachnoid hemorrhage.
This study was aimed to evaluate the influence of an antagonist of heme oxygenase, zinc protoporphyrin IX (ZnPPIX), on the production of endogenous carbon monoxide (CO) and the secondary cerebral injury after subarachnoid hemorrhage (SAH). Wistar rats were divided into non-SAH, SAH, and ZnPPIX groups. Autologus arterial hemolysate was injected into rat cisterna magna to induce SAH. CO and cyclic guanosine monophosphate (cGMP) levels in the brain, and lactate dehydrogenase (LDH) activity in serum were determined 24 hours and 72 hours after cisternal injection. It was found that 24 hours and 72 hours after SAH, the CO contents in SAH group were increased by 20.76% and 37.36%, respectively. CO content in ZnPPIX group was statistically lower than that in SAH group. No obvious change of cGMP content in SAH group was found. However, cGMP content in ZnPPIX group was lower than that in SAH group. Serum LDH activity increased significantly after induction of SAH. LDH activity in ZnPPIX group increased to a greater extent. It was concluded that ZnPPIX aggravates the cerebral injury secondary to experimental SAH by inhibiting the production of endogenous CO. The activation of HO/CO pathway is an intrinsic protective mechanism against cerebral ischemic injury after SAH.
Institute of Microcirculation & Department of Neurology, Affiliated Hospital, Taishan Medical College, Taian, Shandong 271000, China. blsun@tsmc.edu.cn
Bao-Liang
BL
Sun
Wei
W
An
Zuo-Li
ZL
Xia
Cheng-Bi
CB
Zheng
Wen-Xia
WX
Li
Ming-Feng
MF
Yang
Tong
T
Zhao
Wen-Jing
WJ
Ye
D000818:Animals; D002545:Brain Ischemia / Q000209:etiology* / Q000378:metabolism; D002248:Carbon Monoxide / Q000032:analysis / Q000378:metabolism; D006152:Cyclic GMP / Q000032:analysis; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D011524:Protoporphyrins / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013997:Time Factors
D011524:Protoporphyrins; C017803:zinc protoporphyrin; D002248:Carbon Monoxide; D007770:L-Lactate Dehydrogenase; D006419:Heme Oxygenase (Decyclizing); D006152:Cyclic GMP