PMID- 30300655
OWN - NLM
STAT- MEDLINE
DCOM- 20181214
LR  - 20211204
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 212
DP  - 2018 Nov 1
TI  - Effect of valproic acid alone or combined with low dose gamma irradiation in 
      modulating PTZ-induced convulsions in rats involving AKT/m-TOR pathway.
PG  - 261-266
LID - S0024-3205(18)30624-6 [pii]
LID - 10.1016/j.lfs.2018.10.007 [doi]
AB  - AIM: The current study evaluates the anticonvulsant effect of valproic acid (VPA) 
      alone or combined with low dose gamma-irradiation (LDR) against 
      pentylenetetrazol-induced convulsions in rats. MATERIAL AND METHODS: Five groups 
      of rats were used, group I served as normal control, group II served as PTZ- 
      control and the other three groups were pretreated with single LDR(o.5 Gy), 
      VPA(150 mg/kg i.p.5 days) and VPA with LDR respectively before PTZ injection. 
      Racine score, latency and duration of convulsions were assessed. Evaluation of 
      brain neurotransmitters (glutamate and GABA) as well as AKT/m-TOR pathway 
      (protein kinase B [AKT], mammalian target of rapamycin [m-TOR], protein S6 and 
      caspase 3). Measurement of oxidative stress (Malondialdehyde, glutathione and 
      nitric oxide) was carried out. Histopathological examinations of hippocampi were 
      done. KEY FINDINGS: PTZ resulted in behavioural changes (high Racine score, long 
      seizure duration and short latency).PTZ enhanced oxidative stress state (high MDA 
      and NO, as well as low GSH) compared to normal control. VPA alone or combined 
      with LDR ameliorated, the convulsions and caused significant improvement in 
      behavioural changes and other tested parameters compared to normal control. 
      Histopathological examination of hippocampi was carried out to adjoin the 
      biochemical changes. Certain changes were observed after PTZ injection. However, 
      normal pictures of the other tested groups. SIGNIFICANCE: The previously 
      mentioned findings support that LDR purveyed novel anticonvulsant activity which 
      could offer a possible contributor in the basic treatment of convulsions. This 
      effect might be due to modulation of AkT/m-TOR pathway, reduction of oxidative 
      stress and modulation of neurotransmitters.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Lotfy, Dina M
AU  - Lotfy DM
AD  - Department of drug radiation research, National Centre for Radiation Research and 
      Technology, Atomic Energy Authority, Cairo, Egypt. Electronic address: 
      pharmadinaa@yahoo.com.
FAU - Safar, Marwa M
AU  - Safar MM
AD  - Department of pharmacology and toxicology, faculty of pharmacy, Cairo University, 
      Kasr El-Aini St., Cairo 11562, Egypt; Department of Pharmacology and 
      Biochemistry, The British University in Egypt, Suez Desert Road, P.O. Box 43, El 
      Sherouk City, Cairo 11837, Egypt.
FAU - Mohamed, Seham H
AU  - Mohamed SH
AD  - Department of drug radiation research, National Centre for Radiation Research and 
      Technology, Atomic Energy Authority, Cairo, Egypt.
FAU - Kenawy, Sanaa A
AU  - Kenawy SA
AD  - Department of pharmacology and toxicology, faculty of pharmacy, Cairo University, 
      Kasr El-Aini St., Cairo 11562, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20181006
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Anticonvulsants)
RN  - 0 (Convulsants)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - WM5Z385K7T (Pentylenetetrazole)
SB  - IM
MH  - Animals
MH  - Anticonvulsants/*pharmacology
MH  - Convulsants/toxicity
MH  - *Gamma Rays
MH  - Gene Expression Regulation/drug effects/radiation effects
MH  - Male
MH  - Pentylenetetrazole/*toxicity
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Seizures/chemically induced/metabolism/*therapy
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Valproic Acid/*pharmacology
OTO - NOTNLM
OT  - Brain neurotransmitters
OT  - Convulsions
OT  - Low dose gamma irradiation
OT  - Pentylenetetrazole
OT  - Rapamycin
OT  - Valproic acid
EDAT- 2018/10/10 06:00
MHDA- 2018/12/15 06:00
CRDT- 2018/10/10 06:00
PHST- 2018/08/17 00:00 [received]
PHST- 2018/09/29 00:00 [revised]
PHST- 2018/10/05 00:00 [accepted]
PHST- 2018/10/10 06:00 [pubmed]
PHST- 2018/12/15 06:00 [medline]
PHST- 2018/10/10 06:00 [entrez]
AID - S0024-3205(18)30624-6 [pii]
AID - 10.1016/j.lfs.2018.10.007 [doi]
PST - ppublish
SO  - Life Sci. 2018 Nov 1;212:261-266. doi: 10.1016/j.lfs.2018.10.007. Epub 2018 Oct 
      6.