The possible effect of coenzyme Q10 and captopril on acetaminophen-induced encephalopathy in rats: possible influence on autophagy, antioxidant and Na+/K+ ATPase
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Medical Physiology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
Medical Physiology Department, Faculty of Medicine, Jouf University, Sakaka, Saudi Arabia
Histology and Cell Biology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
Submission date: 2020-01-10
Final revision date: 2020-04-13
Acceptance date: 2020-04-17
Online publication date: 2020-11-09
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.

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.

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.

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