PMID- 34780009
OWN - NLM
STAT- MEDLINE
DCOM- 20220211
LR  - 20220211
IS  - 1568-5608 (Electronic)
IS  - 0925-4692 (Linking)
VI  - 29
IP  - 6
DP  - 2021 Dec
TI  - Protective effects of atorvastatin and rosuvastatin on 
      3,4-methylenedioxymethamphetamine (MDMA)-induced spatial learning and memory 
      impairment.
PG  - 1807-1818
LID - 10.1007/s10787-021-00891-y [doi]
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) or "Ecstasy", which has been used for 
      recreational purposes, is shown to impair memory and brain functions. Statins, 
      beyond their efficient cholesterol-lowering impact through inhibition of HMG-COA 
      reductase enzyme, possess multiple actions referred to as pleiotropic effects. In 
      this regard, we aimed to investigate the neuroprotective effects of atorvastatin 
      and rosuvastatin on MDMA-induced neurotoxicity. Adult male Wistar rats received 
      atorvastatin (5, 10, and 20 mg/kg; orally) and rosuvastatin (5, 10, 20 mg/kg; 
      orally) for 21 consecutive days. Then, spatial memory and learning were evaluated 
      by Morris water maze (MWM) test. Rats were intraperitoneally injected with MDMA 
      (2.5, 5, and 10 mg/kg) 30 min before the first training session in 4 training 
      days of MWM task. Afterward, rats were euthanized and their hippocampuses were 
      dissected to evaluate reactive oxygen species (ROS) production, lipid 
      peroxidation (LPO), and caspase-3 and -9 activities. Our findings showed that 
      MDMA (5 and 10 mg/kg) significantly impaired spatial memory functions and 
      dramatically increased ROS production, LPO, and caspase-3 and -9 activities 
      compared to control. Also, atorvastatin (5, 10, and 20 mg/kg) and rosuvastatin 
      (20 mg/kg) significantly improved memory performances and inhibited the elevation 
      of ROS, LPO, and caspase-3 and -9 activities induced by MDMA. In conclusion, the 
      results indicated that MDMA-induced cognitive impairment is followed by oxidative 
      stress and activation of apoptotic pathways in the hippocampus. However, 
      atorvastatin and rosuvastatin suppressed these deleterious consequences of MDMA 
      and revealed protective effects against activation of pathways leading to cell 
      damage.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
FAU - Eslami, Seyyed Majid
AU  - Eslami SM
AD  - Department of Pharmacology, School of Medicine, AJA University of Medical 
      Sciences, Tehran, Iran.
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University 
      of Medical Sciences, Tehran, Iran.
FAU - Khorshidi, Laleh
AU  - Khorshidi L
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University 
      of Medical Sciences, Tehran, Iran.
FAU - Ghasemi, Maryam
AU  - Ghasemi M
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University 
      of Medical Sciences, Tehran, Iran.
FAU - Rashidian, Amir
AU  - Rashidian A
AD  - Department of Pharmacology, School of Medicine, Tehran University of Medical 
      Sciences, Tehran, Iran.
FAU - Mirghazanfari, Mahdi
AU  - Mirghazanfari M
AD  - Department of Physiology and Iranian Medicine, School of Medicine, AJA University 
      of Medical Sciences, Tehran, Iran.
FAU - Nezhadi, Akram
AU  - Nezhadi A
AD  - Neuroscience Research Center, AJA University of Medical Sciences, Tehran, Iran.
FAU - Chamanara, Mohsen
AU  - Chamanara M
AUID- ORCID: 0000-0002-6201-2918
AD  - Department of Pharmacology, School of Medicine, AJA University of Medical 
      Sciences, Tehran, Iran. Chamanaramohsen@gmail.com.
AD  - Toxicology Research Center, AJA University of Medical Sciences, Tehran, Iran. 
      Chamanaramohsen@gmail.com.
FAU - Mirjani, Ruhollah
AU  - Mirjani R
AD  - Department of Genetics and Advanced Medical Technology, Faculty of Medicine, AJA 
      University of Medical Sciences, Tehran, Iran. mirjani.r@gmail.com.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20211115
PL  - Switzerland
TA  - Inflammopharmacology
JT  - Inflammopharmacology
JID - 9112626
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 83MVU38M7Q (Rosuvastatin Calcium)
RN  - A0JWA85V8F (Atorvastatin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Atorvastatin/administration & dosage/*pharmacology
MH  - Cognitive Dysfunction/chemically induced/prevention & control
MH  - Dose-Response Relationship, Drug
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - Maze Learning/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*toxicity
MH  - Neuroprotective Agents/administration & dosage/*pharmacology
MH  - Neurotoxicity Syndromes/etiology/prevention & control
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species/metabolism
MH  - Rosuvastatin Calcium/administration & dosage/*pharmacology
MH  - Spatial Learning/drug effects
MH  - Spatial Memory/drug effects
OTO - NOTNLM
OT  - Ecstasy
OT  - MDMA
OT  - Neuroprotection
OT  - Oxidative stress
OT  - Spatial learning and memory
OT  - Statin
EDAT- 2021/11/16 06:00
MHDA- 2022/02/12 06:00
CRDT- 2021/11/15 12:30
PHST- 2021/04/06 00:00 [received]
PHST- 2021/11/01 00:00 [accepted]
PHST- 2021/11/16 06:00 [pubmed]
PHST- 2022/02/12 06:00 [medline]
PHST- 2021/11/15 12:30 [entrez]
AID - 10.1007/s10787-021-00891-y [pii]
AID - 10.1007/s10787-021-00891-y [doi]
PST - ppublish
SO  - Inflammopharmacology. 2021 Dec;29(6):1807-1818. doi: 10.1007/s10787-021-00891-y. 
      Epub 2021 Nov 15.