Introduction: Induction of autophagy could protect against acetaminophen
(APAP)-induced hepatotoxicity; however, little is known about the role
of autophagy in APAP-induced encephalopathy (APAP-E). This study aimed
to evaluate the effects of coenzyme Q10 (CoQ10) and captopril on APAP-E.
Material and methods: Forty-eight rats were randomly allotted to 4 equal
groups: control, an APAP-E, coenzyme Q10-treated (CoQ10-treated), and
captopril-treated groups. Behavioral tests were conducted. Serum ammonia
and total antioxidant capacity (TAC) and hippocampal Na+/K+ ATPase activity
were measured. The expression levels of hippocampal microtubule-associated
protein light chain 3 (LC3-II) and beclin-1 mRNA were detected using
quantitative polymerase chain reaction (qPCR). General histological, immunohistochemical
staining for glial fibrillary acid protein (GFAP) and electron
microscopy (EM) of the hippocampus were performed.
Results: In the APAP-E group, serum ammonia was increased significantly,
hippocampal LC3-II and beclin-1 mRNA were elevated insignificantly, while
serum TAC and the activity of hippocampal Na+/K+ ATPase were reduced significantly
compared with the control group. APAP-E rats showed remarkable
degenerative changes in CA1 pyramidal neurons in the form of electron-
dense cytoplasm with ill-defined nuclei and accumulation of lysosomal
structure-like dense bodies. Increased immunoreactivity of astrocytes for
GFAP was observed. Treatment with either CoQ10 or captopril significantly
reduced ammonia levels, increased hippocampal LC3-II and beclin-1 mRNA,
increased serum TAC and Na+/K+ ATPase activity, and noticeably ameliorated
the hippocampal neuronal changes. EM revealed restoration of the normal
structure of pyramidal neurons. These effects were more obvious in
CoQ10-treated than captopril-treated rats.
Conclusions: CoQ10 and captopril have neuroprotective effects on APAP-E
via enhancing LC3-II, beclin-1 mRNA expression, serum TAC level and hippocampal
Na+/K+ ATPase activity.