Antiretroviral drugs induce oxidative stress and neuronal damage in the central nervous system

摘要: HIV-associated neurocognitive disorder (HAND), characterized by a wide spectrum of behavioral, cognitive, and motor dysfunctions, continues to affect approximately 50 % HIV(+) patients despite the success combination antiretroviral drug therapy (cART) in periphery. Of note, potential toxicity drugs central nervous system (CNS) remains remarkably underexplored may contribute persistence HAND cART era. Previous studies have shown antiretrovirals (ARVs) be neurotoxic peripheral vivo neurons vitro. Alterations lipid protein metabolism, mitochondrial damage, oxidative stress all play role ARV neurotoxicity. We hypothesized that ARVs also induce cellular stresses CNS, ultimately leading neuronal damage contributing changing clinical pathological picture seen HIV-positive In this report, we show are CNS both pigtail macaques rats vivo. Furthermore, vitro, lead accumulation reactive oxygen species (ROS), induction death. Whereas alone caused some activation endogenous antioxidant response augmentation fumaric acid ester, monomethyl fumarate (MMF), blocked ARV-induced ROS generation, damage/death. These findings implicate as contributor underlying mechanisms neurotoxicity will provide an access point for adjunctive therapies complement reduce patient population.