Prevention of kainic acid-induced changes in nitric oxide level and neuronal cell damage in the rat hippocampus by manganese complexes of curcumin and diacetylcurcumin.

Abstract

Curcumin is a natural antioxidant isolated from the medicinal plant Curcuma longa Linn. We previously reported that manganese complexes of curcumin (Cp-Mn) and diacetylcurcumin (DiAc-Cp-Mn) exhibited potent superoxide dismutase (SOD)-like activity in an in vitro assay. Nitric oxide (NO) is a free radial playing a multifaceted role in the brain and its excessive production is known to induce neurotoxicity. Here, we examined the in vivo effect of Cp-Mn and DiAc-Cp-Mn on NO levels enhanced by kainic acid (KA) and L-arginine (L-Arg) in the hippocampi of awake rats using a microdialysis technique. Injection of KA (10 mg/kg, i.p.) and L-Arg (1000 mg/kg, i.p.) significantly increased the concentration of NO and Cp-Mn and DiAc-Cp-Mn (50 mg/kg, i.p.) significantly reversed the effects of KA and L-Arg without affecting the basal NO concentration. Following KA-induced seizures, severe neuronal cell damage was observed in the CA1 and CA3 subfields of hippocampal 3 days after KA administration. Pretreatment with Cp-Mn and DiAc-Cp-Mn (50 mg/kg, i.p.) significantly attenuated KA-induced neuronal cell death in both CA1 and CA3 regions of rat hippocampus compared with vehicle control, and Cp-Mn and DiAc-Cp-Mn showed more potent neuroprotective effect than their parent compounds, curcumin and diacetylcurcumin. These results suggest that Cp-Mn and DiAc-Cp-Mn protect against KA-induced neuronal cell death by suppression of KA-induced increase in NO levels probably by their NO scavenging activity and antioxidative activity. Cp-Mn and DiAc-Cp-Mn have an advantage to be neuroprotective agents in the treatment of acute brain pathologies associated with NO-induced neurotoxicity and oxidative stress-induced neuronal damage such as epilepsy, stroke and traumatic brain injury.

• Authors: Yaowared Sumanont, Yukihisa Murakami, Michihisa Tohda, Opa Vajragupta, Hiroshi Watanabe, Kinzo Matsumoto
• Journal: Life sciences (Life Sci) Vol. 78 Issue 16 Pg. 1884-91 (Mar 13 2006) ISSN: 0024-3205 [Print] Netherlands
• PMID: 16266725 (Publication Type: Journal Article)

Chemical References

• Excitatory Amino Acid Agonists
• Neuroprotective Agents
• Nitric Oxide
• Manganese
• diacetylcurcumin
• Arginine
• Curcumin
• Kainic Acid

Topics

• Animals
• Apoptosis (drug effects)
• Arginine (pharmacology)
• Curcumin (analogs & derivatives, chemistry, therapeutic use)
• Excitatory Amino Acid Agonists (toxicity)
• Hippocampus (drug effects, metabolism)
• Kainic Acid (toxicity)
• Male
• Manganese (chemistry, therapeutic use)
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (therapeutic use)
• Nitric Oxide (metabolism)
• Oxidative Stress
• Rats
• Rats, Wistar
• Seizures (chemically induced, metabolism, prevention & control)