PMID- 30022232
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20211204
IS  - 1432-1912 (Electronic)
IS  - 0028-1298 (Linking)
VI  - 391
IP  - 10
DP  - 2018 Oct
TI  - Neuroprotective effect of vildagliptin against cerebral ischemia in rats.
PG  - 1133-1145
LID - 10.1007/s00210-018-1537-x [doi]
AB  - Stroke is the leading cause of death worldwide. Dipeptidyl peptidase-4 (DPP-4) 
      inhibitors are a class of anti-diabetic drugs for treatment of type-2 diabetes 
      mellitus. The aim of this study is to evaluate the possible neuroprotective 
      effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent of its 
      anti-diabetic properties in non-diabetic rats subjected to cerebral ischemia. 
      Anesthetized Wistar rats were subjected to either left middle cerebral artery 
      occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. 
      The other three groups were orally administered vildagliptin at 3 dose levels 
      (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral 
      ischemia/reperfusion and till the end of the study. Neurological deficit scores 
      and motor activity were assessed 24 h following reperfusion. Forty-eight hours 
      following reperfusion, rats were euthanized and their left brain hemispheres were 
      harvested and used in biochemical, histopathological, and immunohistochemical 
      investigations. Vildagliptin pretreatment improved neurological deficit score, 
      locomotor activity, and motor coordination in MCAO rats. Moreover, vildagliptin 
      reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), 
      phosphotylinosital 3 kinase (PI3K), phosphoryated of protein kinase B (p-AKT), 
      and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing 
      protein expression of caspase-3. Also, vildagliptin showed a dose-dependent 
      attenuation in neuronal cell loss and histopathological alterations in MCAO rats. 
      This study proves that vildagliptin exerted a neuroprotective effect in a 
      dose-dependent manner as shown in the attenuation of the infarct area, neuronal 
      cell loss, and histopathological damage in MCAO rats, which may be mediated by 
      attenuating neuronal and motor deficits, its antioxidant property, activation of 
      the PI3K/AKT/mTOR pathway, and its anti-apoptotic effect.
FAU - El-Marasy, Salma A
AU  - El-Marasy SA
AUID- ORCID: 0000-0002-8730-0297
AD  - Department of Pharmacology, National Research Centre, Giza, 12622, Egypt. 
      salma_el_marasy@hotmail.com.
FAU - Abdel-Rahman, Rehab F
AU  - Abdel-Rahman RF
AD  - Department of Pharmacology, National Research Centre, Giza, 12622, Egypt.
FAU - Abd-Elsalam, Reham M
AU  - Abd-Elsalam RM
AD  - Department of Pathology, Faculty of Veterinary medicine, Cairo University, Giza, 
      Egypt.
LA  - eng
PT  - Journal Article
DEP - 20180718
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nitriles)
RN  - 0 (Pyrrolidines)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - GAN16C9B8O (Glutathione)
RN  - I6B4B2U96P (Vildagliptin)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/*analogs & derivatives/pharmacology/therapeutic use
MH  - Animals
MH  - Caspase 3/metabolism
MH  - Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use
MH  - Glutathione/metabolism
MH  - Infarction, Middle Cerebral Artery/*drug therapy/metabolism/pathology
MH  - Locomotion/drug effects
MH  - Male
MH  - Malondialdehyde/metabolism
MH  - Neuroprotective Agents/pharmacology/*therapeutic use
MH  - Nitriles/pharmacology/*therapeutic use
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Pyrrolidines/pharmacology/*therapeutic use
MH  - Rats, Wistar
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Vildagliptin
OTO - NOTNLM
OT  - Caspase-3
OT  - Cerebral ischemia
OT  - Dipeptidyl peptidase-4 inhibitor
OT  - Oxidative stress
OT  - PI3K/AKT/mTOR pathway
OT  - Rats
OT  - Vildagliptin
EDAT- 2018/07/20 06:00
MHDA- 2018/11/27 06:00
CRDT- 2018/07/20 06:00
PHST- 2018/03/22 00:00 [received]
PHST- 2018/07/11 00:00 [accepted]
PHST- 2018/07/20 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
PHST- 2018/07/20 06:00 [entrez]
AID - 10.1007/s00210-018-1537-x [pii]
AID - 10.1007/s00210-018-1537-x [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2018 Oct;391(10):1133-1145. doi: 
      10.1007/s00210-018-1537-x. Epub 2018 Jul 18.