1. Pentoxifylline enhances antioxidative capability and promotes mitochondrial biogenesis for improving age-related behavioral deficits
- Author
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Tianyun Zhang, Hui Zhao, Geming Shi, Rui Cui, Yuanxiang Huang, Yu Wang, Guoliang Zhang, Wensheng Yan, Yunxiao Kang, Chunxiao Qi, and Xiaoming Ji
- Subjects
Male ,medicine.medical_specialty ,Aging ,mitochondrial biogenesis ,Phosphodiesterase Inhibitors ,Substantia nigra ,Antioxidants ,Pentoxifylline ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Cyclic adenosine monophosphate ,NRF1 ,Phosphodiesterase inhibitor ,Maze Learning ,Organelle Biogenesis ,Behavior, Animal ,Chemistry ,Dopaminergic ,Brain ,Cell Biology ,TFAM ,aged rats ,Mitochondria ,Rats ,Endocrinology ,pentoxifylline ,Mitochondrial biogenesis ,antioxidative capability ,medicine.drug ,Research Paper - 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.
- Published
- 2020