title: Curcumin supplementation improves mitochondrial and behavioral deficits in experimental model of chronic epilepsy.
abstract: 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 PTZ 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.
authors.affiliation: Department of Biochemistry, Panjab University, Chandigarh 160014, India.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Kaur
authors.affiliation: Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Amanjit
authors.initials: A
authors.lastname: Bal
authors.affiliation: Department of Biochemistry, Panjab University, Chandigarh 160014, India. Electronic address: sandhir@pu.ac.in.
authors.forename: Rajat
authors.initials: R
authors.lastname: Sandhir
mesh_terms: D000818:Animals; D003292:Convulsants / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000187:drug effects / Q000378:metabolism; D004827:Epilepsy / Q000188:drug therapy* / Q000523:psychology; D007696:Kindling, Neurologic / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D051336:Mitochondrial Membranes / Q000187:drug effects; D025261:Mitochondrial Proton-Translocating ATPases / Q000187:drug effects / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D010433:Pentylenetetrazole / Q000494:pharmacology; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000187:drug effects / Q000378:metabolism
chemical_list: D003292:Convulsants; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; C474451:F1F0-ATP synthase; D025261:Mitochondrial Proton-Translocating ATPases; D003474:Curcumin; D010433:Pentylenetetrazole
keywords: Chronic epilepsy; Cognition; Curcumin; Mitochondria; Oxidative stress