title: Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.
abstract: Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells in region specific manner. The study is also revealing the rationale for its clinical use in cognitive impairment and other neurological diseases.
authors.affiliation: Toxicology Division, CSIR-Central Drug Research Institute, Lucknow, India; sarika_singh@cdri.res.in.
authors.forename: Dinesh Kumar
authors.initials: DK
authors.lastname: Verma
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Joshi
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Kunumuri Sivarama
authors.initials: KS
authors.lastname: Raju
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wahajuddin
authors.affiliation: Toxicology Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Rama Kant
authors.initials: RK
authors.lastname: Singh
authors.affiliation: Toxicology Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Sarika
authors.initials: S
authors.lastname: Singh
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001931:Brain Mapping; D005978:Glutathione / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010889:Piracetam / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000494:pharmacology
chemical_list: D012402:Rotenone; D005978:Glutathione; D010889:Piracetam