Acetaminophen induces oligodendrocyte precursor cell death and reactive astroglia in a primary mixed glial cell culture

Abstract

Brain damage in acetaminophen (AP) overdose is associated with liver failure but its direct effects has not been evaluated.AimTo study the effect of toxic and non‐toxic doses of AP on astrocyte and oligodendrocyte precursor cell (OPC) viability in a primary mixed glial cell culture.MYMPrimary cultures of mixed glial cells were carried out according to McCarthy and de Vellis (1980). Cells were treated with vehicle (DMSO) or AP (1 and 20 mM). After 48 hs cell viability was assessed; astrocyte marker (GFAP) and OPC marker (PDGFR‐alpha) expression was evaluated by western‐blot (WB) and immunocytochemistry.ResultsThe 1 mM dose of AP did not produce significant differences in cell viability, while 20 mM exposure decreased in 40% cell viability (P<0.001). The 20 mM dose produced the death of the 90% of the OPC in the culture and a decrease of 89% of PDGFR‐alpha expression (P<0.001) with an increase in GFAP optical density/cell and WB expression (47% and 97% respectively) (P<0.05). The 1mM dose did not produce significant changes in GFAP but produce a 25% significant decreased in PDGFR‐alpha expression (p<0.05).ConclusionAP produces direct toxic effects on glial cells characterized by oligodendrocyte death and the induction of reactive astroglia.