Abstract
We evaluated whether combined treatment with selegiline, a selective MAO-B inhibitor, and EGb 761, a standard extract of Ginkgo biloba, has synergistic effects against ischemic reperfusion injury (IRI) in gerbils. Interestingly, we observed that pretreatment with EGb 761 significantly attenuated selegiline-induced hyperactivity. This finding paralleled striatal fos-related antigen immunoreactivity (FRA-IR) in mice. Four minutes of bilateral carotid artery occlusion caused substantial cell loss in the CA1 of the hippocampus 5 days post-ischemic insult. Pretreatment with EGb 761, with or without selegiline, significantly attenuated this neuronal loss. Combined treatment with EGb 761 plus selegiline was more efficacious in preventing this loss. Synaptosomal formations of protein carbonyl, lipid peroxidation (malondialdehyde (MDA) + 4-hydroxyalkenal (4-HDA)), and reactive oxygen species (ROS) in the hippocampus remained elevated 5 days post-ischemic insult. The antioxidant effects appeared to be most significant in the group treated with EGb 761 plus selegiline. This combined treatment produced more significant attenuation of IRI-induced alterations in intramitochondrial calcium accumulation, the mitochondrial transmembrane potential, and mitochondrial Mn-superoxide dismutase-like immunoreactivity (Mn-SOD-IR) than either treatment alone. Our results suggest that co-administration of EGb 761 and selegiline produces significant neuroprotective effects via suppression of oxidative stress and mitochondrial dysfunction without affecting neurological function.
| Original language | English |
|---|---|
| Pages (from-to) | 157-170 |
| Number of pages | 14 |
| Journal | Neurochemistry International |
| Volume | 45 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 01-07-2004 |
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All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience
- Cell Biology
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Selegiline potentiates the effects of EGb 761 in response to ischemic brain injury. / Kwon, Y. S.; Ann, H. S.; Nabeshima, T.; Shin, E. J.; Kim, W. K.; Jhoo, J. H.; Jhoo, W. K.; Wie, M. B.; Kim, Y. S.; Jang, K. J.; Kim, H. C.
In: Neurochemistry International, Vol. 45, No. 1, 01.07.2004, p. 157-170.Research output: Contribution to journal › Article
TY - JOUR
T1 - Selegiline potentiates the effects of EGb 761 in response to ischemic brain injury
AU - Kwon, Y. S.
AU - Ann, H. S.
AU - Nabeshima, T.
AU - Shin, E. J.
AU - Kim, W. K.
AU - Jhoo, J. H.
AU - Jhoo, W. K.
AU - Wie, M. B.
AU - Kim, Y. S.
AU - Jang, K. J.
AU - Kim, H. C.
PY - 2004/7/1
Y1 - 2004/7/1
N2 - We evaluated whether combined treatment with selegiline, a selective MAO-B inhibitor, and EGb 761, a standard extract of Ginkgo biloba, has synergistic effects against ischemic reperfusion injury (IRI) in gerbils. Interestingly, we observed that pretreatment with EGb 761 significantly attenuated selegiline-induced hyperactivity. This finding paralleled striatal fos-related antigen immunoreactivity (FRA-IR) in mice. Four minutes of bilateral carotid artery occlusion caused substantial cell loss in the CA1 of the hippocampus 5 days post-ischemic insult. Pretreatment with EGb 761, with or without selegiline, significantly attenuated this neuronal loss. Combined treatment with EGb 761 plus selegiline was more efficacious in preventing this loss. Synaptosomal formations of protein carbonyl, lipid peroxidation (malondialdehyde (MDA) + 4-hydroxyalkenal (4-HDA)), and reactive oxygen species (ROS) in the hippocampus remained elevated 5 days post-ischemic insult. The antioxidant effects appeared to be most significant in the group treated with EGb 761 plus selegiline. This combined treatment produced more significant attenuation of IRI-induced alterations in intramitochondrial calcium accumulation, the mitochondrial transmembrane potential, and mitochondrial Mn-superoxide dismutase-like immunoreactivity (Mn-SOD-IR) than either treatment alone. Our results suggest that co-administration of EGb 761 and selegiline produces significant neuroprotective effects via suppression of oxidative stress and mitochondrial dysfunction without affecting neurological function.
AB - We evaluated whether combined treatment with selegiline, a selective MAO-B inhibitor, and EGb 761, a standard extract of Ginkgo biloba, has synergistic effects against ischemic reperfusion injury (IRI) in gerbils. Interestingly, we observed that pretreatment with EGb 761 significantly attenuated selegiline-induced hyperactivity. This finding paralleled striatal fos-related antigen immunoreactivity (FRA-IR) in mice. Four minutes of bilateral carotid artery occlusion caused substantial cell loss in the CA1 of the hippocampus 5 days post-ischemic insult. Pretreatment with EGb 761, with or without selegiline, significantly attenuated this neuronal loss. Combined treatment with EGb 761 plus selegiline was more efficacious in preventing this loss. Synaptosomal formations of protein carbonyl, lipid peroxidation (malondialdehyde (MDA) + 4-hydroxyalkenal (4-HDA)), and reactive oxygen species (ROS) in the hippocampus remained elevated 5 days post-ischemic insult. The antioxidant effects appeared to be most significant in the group treated with EGb 761 plus selegiline. This combined treatment produced more significant attenuation of IRI-induced alterations in intramitochondrial calcium accumulation, the mitochondrial transmembrane potential, and mitochondrial Mn-superoxide dismutase-like immunoreactivity (Mn-SOD-IR) than either treatment alone. Our results suggest that co-administration of EGb 761 and selegiline produces significant neuroprotective effects via suppression of oxidative stress and mitochondrial dysfunction without affecting neurological function.
UR - http://www.scopus.com/inward/record.url?scp=11144356904&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=11144356904&partnerID=8YFLogxK
U2 - 10.1016/j.neuint.2003.10.005
DO - 10.1016/j.neuint.2003.10.005
M3 - Article
C2 - 15082233
AN - SCOPUS:11144356904
VL - 45
SP - 157
EP - 170
JO - Neurochemistry International
JF - Neurochemistry International
SN - 0197-0186
IS - 1
ER -