Protection against kainate neurotoxicity by ginsenosides: attenuation of convulsive behavior, mitochondrial dysfunction, and oxidative stress.
We previously demonstrated that kainic acid (KA)-mediated mitochondrial oxidative stress contributed to hippocampal degeneration and that ginsenosides attenuated KA-induced neurotoxicity and neuronal degeneration. Here, we examined whether ginsenosides affected KA-induced mitochondrial dysfunction and oxidative stress in the rat hippocampus. Treatment with ginsenosides attenuated KA-induced convulsive behavior dose-dependently. KA treatment increased lipid peroxidation and protein oxidation and decreased the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio to a greater degree in the mitochondrial fraction than in the hippocampal homogenate. KA treatment resulted in decreased Mn-superoxide dismutase expression and diminished the mitochondrial membrane potential. Furthermore, KA treatment increased intramitochondrial Ca(2+) and promoted ultrastructural degeneration in hippocampal mitochondria. Treatment with ginsenosides dose-dependently attenuated convulsive behavior and the KA-induced mitochondrial effects. Protection appeared to be more evident in mitochondria than in tissue homogenates. Collectively, the results suggest that ginsenosides prevent KA-induced neurotoxicity by attenuating mitochondrial oxidative stress and mitochondrial dysfunction.
Shin
Eun-Joo
EJ
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, South Korea.
Jeong
Ji Hoon
JH
Kim
A-Young
AY
Koh
Young Ho
YH
Nah
Seung-Yeoul
SY
Kim
Won-Ki
WK
Ko
Kwang Ho
KH
Kim
Hyun Ji
HJ
Wie
Myung-Bok
MB
Kwon
Yong Soo
YS
Yoneda
Yukio
Y
Kim
Hyoung-Chun
HC
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D036145:Ginsenosides / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D007608:Kainic Acid / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism
D000927:Anticonvulsants; D000975:Antioxidants; D036145:Ginsenosides; D018696:Neuroprotective Agents; D013482:Superoxide Dismutase; D005978:Glutathione; D007608:Kainic Acid; D002118:Calcium