Effects of manganese complexes of curcumin and diacetylcurcumin on kainic acid-induced neurotoxic responses in the rat hippocampus.
This study aimed to investigate the mechanism underlying the protective effects of manganese complexes of curcumin (Cp-Mn) and diacetylcurcumin (DiAc-Cp-Mn) on kainic acid (KA)-induced excitotoxicity in the rat hippocampus. Systemic injection of KA (10 mg/kg, i.p.) caused seizures and increased the expression of neurotoxic markers, immediate early genes [c-jun, cyclooxygenase 2 (COX-2), brain-derived neurotrophic factor (BDNF), and heat shock protein 70 (hsp70)] and a delayed response gene [inducible nitric oxide synthase (iNOS)], which were measured at 6 and 72 h after KA injection, respectively, in the hippocampus. Pretreatment with Cp-Mn (50 mg/kg, i.p.) and DiAc-Cp-Mn (50 mg/kg, i.p.) but not with curcumin (50 mg/kg, i.p.) delayed the onset of KA-induced seizure without affecting the seizure score. KA injection induced c-Fos immunoreactivity in DG, CA1, and CA3 hippocampal regions, the expression of which peaked at 6 h after injection. Cp-Mn and DiAc-Cp-Mn treatment significantly decreased c-Fos expression elicited by KA. Moreover, Cp-Mn and DiAc-Cp-Mn administration suppressed the KA-induced expression of c-jun, COX-2, BDNF, and iNOS mRNA, whereas curcumin attenuated only iNOS mRNA expression. No compounds tested had an effect on KA-induced hsp70 expression. It is therefore likely that in addition to radical scavenging and SOD-like activities, the suppression of potential neuronal injury marker expression by Cp-Mn and DiAc-Cp-Mn, contributes to the neuroprotective activities of these compounds, which are superior to those of curcumin, on KA-induced excitotoxicity in the hippocampus. These results suggest the beneficial effects of Cp-Mn, and DiAc-Cp-Mn on the treatment of excitotoxicity-induced neurodegenerative diseases.
Sumanont
Yaowared
Y
Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
Murakami
Yukihisa
Y
Tohda
Michihisa
M
Vajragupta
Opa
O
Watanabe
Hiroshi
H
Matsumoto
Kinzo
K
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D016923:Cell Death / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control