PMID- 21463622
OWN - NLM
STAT- MEDLINE
DCOM- 20110909
LR  - 20131121
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 659
IP  - 2-3
DP  - 2011 Jun 1
TI  - Modulation of nitrergic pathway by sesamol prevents cognitive deficits and 
      associated biochemical alterations in intracerebroventricular streptozotocin 
      administered rats.
PG  - 177-86
LID - 10.1016/j.ejphar.2011.03.026 [doi]
AB  - Alzheimer's disease is a neurodegenerative disorder characterized by progressive 
      cognitive decline and widespread loss of neurons and their synapses in the 
      cerebral cortex and hippocampus. Increasing evidence indicates that factors such 
      as oxidative-nitrergic stress, glutathione depletion, impaired protein metabolism 
      and cholinergic deficit can interact in a vicious cycle, which is central to 
      Alzheimer's disease pathogenesis. Intracerebroventricular (i.c.v.) streptozotocin 
      induced-cognitive impairment has been widely used as an experimental paradigm to 
      study Alzheimer's disease. In the present study, i.c.v. streptozotocin produced 
      significant cognitive deficits as measured in Morris water maze and elevated plus 
      maze task coupled with increased serum TNF-alpha levels and marked rise in brain 
      acetylcholinesterase and oxidative-nitrergic stress in female Wistar rats. 
      Sesamol (5-hydroxy-1,3-benzodioxole or 3,4-methylenedioxyphenol), a potent 
      anti-oxidant and anti-inflammatory molecule markedly improved cognitive 
      impairment, reduced acetylcholinesterase activity, TNF-alpha levels and attenuated 
      oxidative-nitrergic stress in brain of i.c.v.-streptozotocin treated rats. 
      Administration of L-arginine (125 mg/kg i.p), a nitric oxide donor, alone to 
      i.c.v.-streptozotocin treated rats accentuated behavioral and biochemical 
      deficits and also abolished the protective effect of sesamol (8 mg/kg). L-NAME 
      (10 mg/kgi.p.), a non-specific NOS inhibitor significantly restored all the 
      behavioral and biochemical indices in i.c.v.-streptozotocin rats. Moreover, 
      combination of L-NAME with sub-effective dose of sesamol (4 mg/kg) potentiated 
      its protective effect. Our findings demonstrate the effectiveness of sesamol in 
      preventing intracerebroventricular streptozotocin-induced cognitive deficits by 
      modulating nitrergic signaling and oxido-inflammatory cascade.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Misra, Shubham
AU  - Misra S
AD  - Pharmacology Research Laboratory, University Institute of Pharmaceutical 
      Sciences, UGC Center of Advanced Study, Panjab University, Chandigarh-160014, 
      India.
FAU - Tiwari, Vinod
AU  - Tiwari V
FAU - Kuhad, Anurag
AU  - Kuhad A
FAU - Chopra, Kanwaljit
AU  - Chopra K
LA  - eng
PT  - Journal Article
DEP - 20110402
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Antioxidants)
RN  - 0 (Benzodioxoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Neurotoxins)
RN  - 0 (Phenols)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 5W494URQ81 (Streptozocin)
RN  - 94IEA0NV89 (sesamol)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Acetylcholinesterase/metabolism
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Arginine/pharmacology
MH  - Behavior, Animal/drug effects/physiology
MH  - Benzodioxoles/*pharmacology
MH  - Cognition Disorders/*chemically induced/metabolism/physiopathology/*prevention & 
      control
MH  - Drug Administration Routes
MH  - Drug Interactions
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Lipid Peroxidation/drug effects
MH  - Maze Learning/drug effects
MH  - Motor Activity/drug effects/physiology
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Neurotoxins/administration & dosage/toxicity
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase/antagonists & inhibitors
MH  - Phenols/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/*drug effects
MH  - Streptozocin/*administration & dosage/*toxicity
MH  - Stress, Physiological/drug effects
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2011/04/06 06:00
MHDA- 2011/09/10 06:00
CRDT- 2011/04/06 06:00
PHST- 2010/09/22 00:00 [received]
PHST- 2011/02/25 00:00 [revised]
PHST- 2011/03/21 00:00 [accepted]
PHST- 2011/04/06 06:00 [entrez]
PHST- 2011/04/06 06:00 [pubmed]
PHST- 2011/09/10 06:00 [medline]
AID - S0014-2999(11)00338-4 [pii]
AID - 10.1016/j.ejphar.2011.03.026 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2011 Jun 1;659(2-3):177-86. doi: 10.1016/j.ejphar.2011.03.026. 
      Epub 2011 Apr 2.