PMID- 33231568
OWN - NLM
STAT- MEDLINE
DCOM- 20210513
LR  - 20210513
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 12
IP  - 24
DP  - 2020 Nov 20
TI  - Pentoxifylline enhances antioxidative capability and promotes mitochondrial 
      biogenesis for improving age-related behavioral deficits.
PG  - 25487-25504
LID - 10.18632/aging.104155 [doi]
AB  - Pentoxifylline (PTX) is a non-specific phosphodiesterase inhibitor with 
      pleiotropic effects that is routinely used to treat peripheral vascular disease. 
      In this study, we tested whether PTX could also counteract the detrimental 
      effects of aging in the brain. To accomplish that, we treated aged rats with PTX 
      and measured resulting behavioral alterations as well as changes in dopaminergic 
      neurochemical levels, oxidative balance markers, mitochondrial function, nuclear 
      factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator activated 
      receptor-gamma coactivator 1-alpha (PGC-1alpha) and downstream gene expression, and 
      cyclic adenosine monophosphate (cAMP) content in the brain. The results 
      demonstrated that PTX improved motor and cognitive deficits and restored levels 
      of dopamine and its metabolites in the brains of aged rats. PTX also reduced 
      malondialdehyde levels and increased the GSH/GSSG ratio, mitochondrial ATP, 
      nuclear Nrf2, and cAMP levels, and upregulated PGC-1alpha, nuclear respiratory factor 
      1, and mitochondrial transcription factor A expression in the substantia nigra 
      and hippocampus of aged rats. Thus, increased nuclear Nrf2 levels and 
      upregulation of PGC-1alpha, which enhance antioxidative capability and promote 
      mitochondrial biogenesis, may be responsible for PTX-induced amelioration of 
      behavioral deficits in aged rats.
FAU - Wang, Yu
AU  - Wang Y
AD  - Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China.
FAU - Kang, Yunxiao
AU  - Kang Y
AD  - Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China.
FAU - Qi, Chunxiao
AU  - Qi C
AD  - Department of Anatomy, Hebei Medical University, Shijiazhuang 050017, China.
FAU - Zhang, Tianyun
AU  - Zhang T
AD  - Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China.
FAU - Zhao, Hui
AU  - Zhao H
AD  - Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China.
FAU - Ji, Xiaoming
AU  - Ji X
AD  - Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China.
FAU - Yan, Wensheng
AU  - Yan W
AD  - Department of Sports Medicine, Hebei Sport University, Shijiazhuang 050017, 
      China.
FAU - Huang, Yuanxiang
AU  - Huang Y
AD  - Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China.
FAU - Cui, Rui
AU  - Cui R
AD  - Department of Anatomy, Hebei Medical University, Shijiazhuang 050017, China.
FAU - Zhang, Guoliang
AU  - Zhang G
AD  - Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China.
AD  - Department of Anatomy, Hebei Medical University, Shijiazhuang 050017, China.
FAU - Shi, Geming
AU  - Shi G
AD  - Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China.
AD  - Neuroscience Research Center, Hebei Medical University, Shijiazhuang 050017, 
      China.
AD  - Hebei Key Laboratory of Neurodegenerative Disease Mechanism, Hebei Medical 
      University, Shijiazhuang 050017, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201120
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Antioxidants)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - SD6QCT3TSU (Pentoxifylline)
SB  - IM
MH  - Aging/*drug effects/metabolism
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Behavior, Animal/*drug effects
MH  - Brain/*drug effects/metabolism
MH  - Male
MH  - Maze Learning/drug effects
MH  - Mitochondria/*drug effects
MH  - Organelle Biogenesis
MH  - Pentoxifylline/*pharmacology
MH  - Phosphodiesterase Inhibitors/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC7803534
OTO - NOTNLM
OT  - aged rats
OT  - antioxidative capability
OT  - mitochondrial biogenesis
OT  - pentoxifylline
COIS- CONFLICTS OF INTEREST: The authors declare that there are no conflicts of 
      interest.
EDAT- 2020/11/25 06:00
MHDA- 2021/05/14 06:00
PMCR- 2020/12/31
CRDT- 2020/11/24 12:11
PHST- 2020/05/06 00:00 [received]
PHST- 2020/09/09 00:00 [accepted]
PHST- 2020/11/25 06:00 [pubmed]
PHST- 2021/05/14 06:00 [medline]
PHST- 2020/11/24 12:11 [entrez]
PHST- 2020/12/31 00:00 [pmc-release]
AID - 104155 [pii]
AID - 10.18632/aging.104155 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2020 Nov 20;12(24):25487-25504. doi: 10.18632/aging.104155. 
      Epub 2020 Nov 20.