The Ginkgo biloba extract, EGb 761, fails to reduce brain infarct size in rats after transient, middle cerebral artery occlusion in conditions of unprevented, ischemia-induced fever.
There is much biochemical evidence, but very few studies in animal models of stroke in vivo, to suggest that Ginkgo biloba (EGb 761) may offer neuroprotection against regional, ischemic brain damage; additional investigations are needed to ensure future clinical trials. This study reports the effects of EGb 761 given acutely or chronically before ischemia. Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h and the brain infarct size was assessed 24 h later. Dipyrone (100 mg/kg, i.p.) was injected 30 min before ischemia, and 2.5 and 5.5 h after ischemia, to reduce ischemia-induced fever. EGb 761 (Tebonin) was given acutely (200 mg/kg, p.o., 60 min before ischemia) or chronically (100 mg/kg, p.o., once daily, for 14 days before ischemia). Acute or chronic treatment with EGb 761, either alone or in combination with dipyrone, did not reduce the infarct size compared with saline alone (p > 0.05). Dipyrone failed to prevent ischemia-induced fever during the intra-ischemic period (p > 0.05 vs saline; p < 0.001 vs sham). In the reperfusion phase, dipyrone reduced fever to normothermic levels in the group treated acutely with EGb 761 (p < 0.01 vs saline, p > 0.05 vs sham) but not after chronic EGb 761 (p < 0.01 vs sham), indicating possible pharmacokinetic interaction. In conclusion, within the context of unprevented, ischemia-induced fever, the present results demonstrate that EGb 761 has no significant effect on brain infarct size.
de Lima
Keli Carina Miltus
KC
Department of Pharmacy and Pharmacology, Health Science Center, Pharmaceutical Sciences Post-Graduation Program, State University of Maringá, Av. Colombo, 5790, CEP 87020-900 Maringá, Paraná, Brazil.
Schilichting
Carmen Lúcia Ruiz
CL
Junior
Lourival Augusto Cestari
LA
da Silva
Flávia Munhoz
FM
Benetoli
Arcélio
A
Milani
Humberto
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D004177:Dipyrone / Q000627:therapeutic use; D005334:Fever / Q000188:drug therapy / Q000209:etiology; D020441:Ginkgo biloba; D020244:Infarction, Middle Cerebral Artery / Q000517:prevention & control*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D000096983:Ginkgo Extract
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004177:Dipyrone; D018696:Neuroprotective Agents; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract