SELECTIVE PURKINJE NEURONAL DAMAGE BY ACUTE ACETAMINOPHEN (APAP) INTOXICATION IS ASSOCIATED WITH OXIDATIVE STRESS IN THE CEREBELLUM OF RATS

ALLEGRO, JB; GHANEM, CI; ORBEA, L; MANAUTOU, JE; VIGO, MB; ROMEO, AC

Mar del Plata

Congreso; LXVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2022

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC)

Previously, we have demonstrated that APAP overdosing, which does not result in acute liver failure (ALF), reduces locomotor activity (~50%) and dopaminergic markers. Furthermore, decreased neuronal processes and astrogliosis in brain areas controlling locomotion are also observed. Therefore, the aim of the present work was to evaluate the effect of acute APAP intoxication on the structure and the principal constituent cells of the cerebellum, the main region of the central nervous system governing motor coordination and learning. For this purpose, male Wistar rats were dosed with APAP (1g/kg; i.p., n=5) or vehicle (n=5). 24h later, the cerebellum was processed to examine histopathological changes and the presence of edema. Also, the protein expression of markers of astrocyte structure (Glial fibrillary protein; Gfap), and neuronal structure (Neurofilament heavy; NF200) was determined by Western blotting, and oxidative stress status was also determined indirectly by analysis of nuclear translocation of Nrf2, a master regulator of antioxidant responses. Histological cerebellar tissue analysis by hematoxylin and eosin staining revealed no discernible ultrastructural changes or edema (also confirmed by tissue water content). However, a significantly decreased by 24.5% in the number of Purkinje neurons in the APAP treated group (p