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Research Paper|Volume 12, Issue 24|pp 25487—25504

Pentoxifylline enhances antioxidative capability and promotes mitochondrial biogenesis for improving age-related behavioral deficits

Yu Wang1, Yunxiao Kang1, Chunxiao Qi2, Tianyun Zhang1, Hui Zhao1, Xiaoming Ji1, Wensheng Yan3, Yuanxiang Huang1, Rui Cui2, Guoliang Zhang1,2, Geming Shi1,4,5
  • 1Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China
  • 2Department of Anatomy, Hebei Medical University, Shijiazhuang 050017, China
  • 3Department of Sports Medicine, Hebei Sport University, Shijiazhuang 050017, China
  • 4Neuroscience Research Center, Hebei Medical University, Shijiazhuang 050017, China
  • 5Hebei Key Laboratory of Neurodegenerative Disease Mechanism, Hebei Medical University, Shijiazhuang 050017, China
Received: May 6, 2020Accepted: September 9, 2020Published: November 20, 2020
https://doi.org/10.18632/aging.104155

Copyright: © 2020 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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-1α) 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-1α, 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-1α, which enhance antioxidative capability and promote mitochondrial biogenesis, may be responsible for PTX-induced amelioration of behavioral deficits in aged rats.