PMID- 25689821
OWN - NLM
STAT- MEDLINE
DCOM- 20160122
LR  - 20150509
IS  - 1878-4216 (Electronic)
IS  - 0278-5846 (Linking)
VI  - 60
DP  - 2015 Jul 3
TI  - ADIOL protects against 3-NP-induced neurotoxicity in rats: Possible impact of its 
      anti-oxidant, anti-inflammatory and anti-apoptotic actions.
PG  - 36-51
LID - S0278-5846(15)00031-7 [pii]
LID - 10.1016/j.pnpbp.2015.02.005 [doi]
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder with a wide 
      spectrum of cognitive, behavioral and motor abnormalities. The mitochondrial 
      toxin 3-nitropropionic acid (3-NP) effectively induces specific behavioral 
      changes and selective striatal lesions similar to that observed in HD. Some 
      neurosteroids, synthesized in neurons and glial cells, previously showed 
      neuroprotective abilities. 5-Androstene-3beta-17beta-diol (ADIOL) is a major metabolite 
      of dehydroepiandrosterone (DHEA) with previously reported anti-inflammatory, 
      anti-apoptotic and neuroprotective activities. The neuroprotective potential of 
      ADIOL in HD was not previously investigated. Therefore, the present study 
      investigated the neuroprotective effects of ADIOL against 3-NP-induced behavioral 
      changes, oxidative stress, inflammation and apoptosis. Intraperitoneal 
      administration of 3-NP (20mg/kg) for 4 consecutive days in rats caused 
      significant loss in body weight, reduced prepulse inhibition (PPI) of acoustic 
      startle response, locomotor hypoactivity with altered cortical/striatal 
      histological structure, increased cortical/striatal oxidative stress, 
      inflammation and apoptosis. Administration of ADIOL (25mg/kg, s.c.) for two days 
      before 3-NP significantly attenuated the reduction in body weights and PPI, 
      increased locomotor activity and restored cortical/striatal histological 
      structure nearly to normal. Moreover, it displayed anti-oxidant, 
      anti-inflammatory and anti-apoptotic activities as evidenced by the elevation of 
      cortical and striatal reduced glutathione levels, reductions of cortical and 
      striatal malondialdehyde, striatal tumor necrosis factor alpha and interleukin-6 
      levels. Only a small number of iNOS and caspase-3 positive cells were detected in 
      sections from rats pretreated with ADIOL. This study suggests a potential 
      neuroprotective role of ADIOL against 3-NP-induced Huntington's disease-like 
      manifestations. Such neuroprotection can be attributed to its anti-oxidant, 
      anti-inflammatory and anti-apoptotic activities.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Hanna, Diana M F
AU  - Hanna DM
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams 
      University, Cairo, Egypt.
FAU - Tadros, Mariane G
AU  - Tadros MG
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams 
      University, Cairo, Egypt. Electronic address: mirogeogo@yahoo.com.
FAU - Khalifa, Amani E
AU  - Khalifa AE
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams 
      University, Cairo, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20150214
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Antioxidants)
RN  - 0 (Cytokines)
RN  - 0 (Neurotoxins)
RN  - 0 (Nitro Compounds)
RN  - 0 (Propionates)
RN  - 409J2J96VR (Androstenedione)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - 571-36-8 (5-androstene-3,17-dione)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 3.4.22.- (Caspase 3)
RN  - GAN16C9B8O (Glutathione)
RN  - QY4L0FOX0D (3-nitropropionic acid)
SB  - IM
MH  - Analysis of Variance
MH  - Androstenedione/*therapeutic use
MH  - Animals
MH  - Antioxidants/*therapeutic use
MH  - Apoptosis/drug effects
MH  - Body Weight/drug effects
MH  - Caspase 3/metabolism
MH  - Catalase/metabolism
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Glutathione/metabolism
MH  - Male
MH  - Malondialdehyde/metabolism
MH  - Motor Activity/drug effects
MH  - Neurotoxicity Syndromes/*etiology/*prevention & control
MH  - Neurotoxins/*toxicity
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Nitro Compounds/*toxicity
MH  - Propionates/*toxicity
MH  - Rats
MH  - Reflex, Startle/drug effects
OTO - NOTNLM
OT  - 3-Nitropropionic acid
OT  - ADIOL
OT  - Apoptosis
OT  - Neuroinflammation
OT  - Prepulse inhibition
EDAT- 2015/02/18 06:00
MHDA- 2016/01/23 06:00
CRDT- 2015/02/18 06:00
PHST- 2014/11/12 00:00 [received]
PHST- 2015/02/08 00:00 [revised]
PHST- 2015/02/09 00:00 [accepted]
PHST- 2015/02/18 06:00 [entrez]
PHST- 2015/02/18 06:00 [pubmed]
PHST- 2016/01/23 06:00 [medline]
AID - S0278-5846(15)00031-7 [pii]
AID - 10.1016/j.pnpbp.2015.02.005 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jul 3;60:36-51. doi: 
      10.1016/j.pnpbp.2015.02.005. Epub 2015 Feb 14.