Oxycodone suppresses the lipopolysaccharide-induced neuroinflammation by downregulating nuclear factor-κB in hippocampal astrocytes of Sprague-Dawley rats.

Abstract

Neuroinflammation is a common pathogenic mechanism in several neurodegenerative diseases, and glial cells are the primary inflammatory mediators of the central nervous system (CNS). Acute neuronal injury, infection, and chronic neurodegeneration may induce astrocyte activation, which is a response characterized by hyperproliferation and release of multiple inflammatory signaling factors. The opioid analgesic oxycodone has demonstrated anti-inflammatory efficacy in peripheral tissue, but its effects on the CNS have not been studied. We evaluated the inhibitory effects of oxycodone on astrocyte activation and proinflammatory mediator production in response to lipopolysaccharide (LPS). Our results showed that oxycodone (5-20 μg/ml) dose-dependently inhibited the LPS-induced astrocytosis, as measured by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide and bromodeoxyuridine assays, as well as the overexpression of glial fibrillary acidic protein, which are two hallmarks of reactive astrogliosis in neurodegenerative diseases. Oxycodone also decreased both the mRNA and protein expression levels of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β. Besides, oxycodone increased the expression of the nuclear factor kappa-B (NF-κB) endogenous inhibitor IκB-α, and blocked NF-κB translocation to the nucleus. The anti-inflammatory efficacy of oxycodone on rat astrocytes increased with pretreatment duration. These results suggest that oxycodone can suppress neuroinflammation by inhibiting NF-κB signaling in astrocytes. Targeting the astrocytic NF-κB-mediated inflammatory response may be an effective therapeutic strategy against diseases involving neuroinflammatory damage.