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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.
Life Sci. 2006 Mar 13; 78(16):1884-91.LS

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+Show Affiliations

Division of Medicinal Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16266725

Citation

Sumanont, Yaowared, et al. "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." Life Sciences, vol. 78, no. 16, 2006, pp. 1884-91.
Sumanont Y, Murakami Y, Tohda M, et al. 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. Life Sci. 2006;78(16):1884-91.
Sumanont, Y., Murakami, Y., Tohda, M., Vajragupta, O., Watanabe, H., & Matsumoto, K. (2006). 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. Life Sciences, 78(16), 1884-91.
Sumanont Y, et al. 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. Life Sci. 2006 Mar 13;78(16):1884-91. PubMed PMID: 16266725.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Sumanont,Yaowared, AU - Murakami,Yukihisa, AU - Tohda,Michihisa, AU - Vajragupta,Opa, AU - Watanabe,Hiroshi, AU - Matsumoto,Kinzo, Y1 - 2005/11/02/ PY - 2005/03/01/received PY - 2005/08/27/accepted PY - 2005/11/4/pubmed PY - 2006/4/12/medline PY - 2005/11/4/entrez SP - 1884 EP - 91 JF - Life sciences JO - Life Sci VL - 78 IS - 16 N2 - 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. SN - 0024-3205 UR - https://www.unboundmedicine.com/medline/citation/16266725/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_ DB - PRIME DP - Unbound Medicine ER -