Abstract
Excessively generated reactive oxygen species are associated with age-related neurodegenerative diseases. We investigated whether scavenging of reactive oxygen species in the brain by orally administered redox nanoparticles, prepared by self-assembly of redox polymers possessing antioxidant nitroxide radicals, facilitates the recovery of cognition in 17-week-old senescence-accelerated prone (SAMP8) mice. The redox polymer was delivered to the brain after oral administration of redox nanoparticles via a disintegration of the nanoparticles in the stomach and absorption of the redox polymer at small intestine to the blood. After treatment for one month, levels of oxidative stress in the brain of SAMP8 mice were remarkably reduced by treatment with redox nanoparticles, compared to that observed with low-molecular-weight nitroxide radicals, resulting in the amelioration of cognitive impairment with increased numbers of surviving neurons. Additionally, treatment by redox nanoparticles did not show any detectable toxicity. These findings indicate the potential of redox polymer nanotherapeutics for treatment of the neurodegenerative diseases.
Highlights
Aging increases the risk of neurodegenerative diseases, such as Alzheimer’s disease (AD), which mostly affect quality of life in the elderly
After oral administration of RNPN, a sharp triplet electron spin resonance (ESR) signal was observed in the stomach, indicating that the disintegration of RNPN in the stomach and exposure of nitroxide radical from the core of RNPN occurred owing to the acidic microenvironment
We confirmed that orally administered TEMPOL is eliminated within 1 h from the blood [7], which is in sharp contrast to orally administered RNPN
Summary
Aging increases the risk of neurodegenerative diseases, such as Alzheimer’s disease (AD), which mostly affect quality of life in the elderly. The average human life span has increased because of progress in medical and health care, the socioeconomic burden of the elderly is a concern in developed countries. The production of ROS dramatically increases, and endogenous antioxidants fail to completely scavenge all of the ROS, followed by production of oxidative components. An increase in the oxidative stress in the brain is reported to be involved in aging-related neural dysfunction and/or learning and memory deficiency [1]. Previous studies have suggested that an increase in the expression of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), in the brain is involved in aging-related neural dysfunction and/or learning and memory deficiency in animals. The promising low-molecularweight (LMW) antioxidant, vitamin E, was reported to show slight efficacy such as slowing of functional decline, in clinical trials of AD, a complete recovery was not observed [2, 3]
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