Curcumin supplementation improves mitochondrial and behavioral deficits in experimental model of chronic epilepsy

被引:33
作者
Kaur, Harpreet [1 ]
Bal, Amanjit [2 ]
Sandhir, Rajat [1 ]
机构
[1] Panjab Univ, Dept Biochem, Chandigarh 160014, India
[2] Postgrad Inst Med Educ & Res, Dept Histopathol, Chandigarh 160012, India
关键词
Curcumin; Chronic epilepsy; Mitochondria; Cognition; Oxidative stress; NEURONAL CELL-DEATH; OXIDATIVE STRESS; INDUCED SEIZURES; IN-VIVO; DYSFUNCTION; MEMORY; HIPPOCAMPUS; GLUTAMATE; MECHANISM; DISEASE;
D O I
10.1016/j.pbb.2014.08.001
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
The present study was aimed to investigate the potential beneficial effect of curcumin, a polyphenol with pleiotropic properties, on mitochondrial dysfunctions, oxidative stress and cognitive deficits in a kindled model of epilepsy. Kindled epilepsy was induced in rats by administering a sub-convulsive dose of pentylenetetrazole (PTZ, 40 mg/kg body weight) every alternate day for 30 days. PTZ administered rats exhibited marked cognitive deficits assessed using active and passive avoidance tasks. This was accompanied by a significant decrease in NADH:cytochrome-c reductase (complex I) and cytochrome-c oxidase (complex IV) activities along with an increase in ROS, lipid peroxidation and protein carbonyls. The levels of glutathione also decreased in the cortex and hippocampus. Electron micrographs revealed disruption of mitochondrial membrane integrity with distorted cristae in PTZ treated animals. Histopathological examination showed pyknotic nuclei and cell loss in the hippocampus as well as in the cortex of PTZ treated animals. Curcumin administration at a dose of 100 mg/kg, p.o. throughout the treatment paradigm was able to ameliorate cognitive deficits with no significant effect on seizure score. Curcumin was able to restore the activity of mitochondrial complexes. In addition, significant reduction in ROS generation, lipid peroxidation and protein carbonyls was observed in VIZ animals supplemented with curcumin. Moreover, glutathione levels were also restored in PTZ treated rats supplemented with curcumin. Curcumin protected mitochondria from seizure induced structural alterations. Further, the curcumin supplemented PTZ rats had normal cell morphology and reduced cell loss. These results suggest that curcumin supplementation has potential to prevent mitochondrial dysfunctions and oxidative stress with improved cognitive functions in a chronic model of epilepsy. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:55 / 64
页数:10
相关论文
共 93 条
  • [1] Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature
    Anand, Preetha
    Thomas, Sherin G.
    Kunnumakkara, Ajaikumar B.
    Sundaram, Chitra
    Harikumar, Kuzhuvelil B.
    Sung, Bokyung
    Tharakan, Sheeja T.
    Misra, Krishna
    Priyadarsini, Indira K.
    Rajasekharan, Kallikat N.
    Aggarwal, Bharat B.
    [J]. BIOCHEMICAL PHARMACOLOGY, 2008, 76 (11) : 1590 - 1611
  • [2] GLUTAMATE-INDUCED NEURONAL DEATH - A SUCCESSION OF NECROSIS OR APOPTOSIS DEPENDING ON MITOCHONDRIAL-FUNCTION
    ANKARCRONA, M
    DYPBUKT, JM
    BONFOCO, E
    ZHIVOTOVSKY, B
    ORRENIUS, S
    LIPTON, SA
    NICOTERA, P
    [J]. NEURON, 1995, 15 (04) : 961 - 973
  • [3] Asadi-Shekaari Majid, 2012, Avicenna Journal of Medical Biotechnology, V4, P155
  • [4] Whole mitochondrial DNA variations in hippocampal surgical specimens and blood samples with high-throughput sequencing: A case of mesial temporal lobe epilepsy with hippocampal sclerosis
    Azakli, Hulya
    Gurses, Candan
    Arikan, Muzaffer
    Aydoseli, Aydin
    Aras, Yavuz
    Sencer, Altay
    Gokyigit, Aysen
    Bilgic, Bilge
    Ustek, Duran
    [J]. GENE, 2013, 529 (01) : 190 - 194
  • [5] Cyclooxygenase-2 selective inhibitors aggravate kainic acid induced seizure and neuronal cell death in the hippocampus
    Baik, EJ
    Kim, EJ
    Lee, SH
    Moon, CH
    [J]. BRAIN RESEARCH, 1999, 843 (1-2) : 118 - 129
  • [6] Intracellular ROS Protection Efficiency and Free Radical-Scavenging Activity of Curcumin
    Barzegar, Abolfazl
    Moosavi-Movahedi, Ali A.
    [J]. PLOS ONE, 2011, 6 (10):
  • [7] Brustovetsky N, 2003, J NEUROSCI, V23, P4858
  • [8] CAVAZOS JE, 1994, J NEUROSCI, V14, P3106
  • [9] Gabapentin, A GABA analogue, enhances cognitive performance in mice
    Celikyurt, Ipek Komsuoglu
    Mutlu, Oguz
    Ulak, Guner
    Akar, Furuzan Yildiz
    Erden, Faruk
    [J]. NEUROSCIENCE LETTERS, 2011, 492 (02) : 124 - 128
  • [10] The potential role of mitochondrial dysfunction in seizure-associated cell death in the hippocampus and epileptogenesis
    Chen, Shang-Der
    Chang, Alice Y. W.
    Chuang, Yao-Chung
    [J]. JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 2010, 42 (06) : 461 - 465