Hepatoprotective effect of blocking N-methyl-d-aspartate receptors in male albino rats exposed to acute and repeated restraint stress.
Stress affects many organs in addition to the brain, including the liver. We assessed the effects on the liver of blocking N-methyl-d-aspartate (NMDA) glutamate receptors with memantine in acute and repeated restraint stress. Forty-two male albino rats were divided into 7 groups; control, acute restraint stress (ARS), ARS + memantine, repeated restraint stress, repeated restraint + memantine, and positive control groups. We measured serum iron, zinc, alanine transferase and aspartame transferase, hepatic malondialdehyde, tumor necrosis factor-α (TNF-α), glutathione peroxidase, superoxide dismutase, metallothionein content, zinc transporter ZRT/IRT-like protein 14 mRNA expression, and hepcidin expression. We conducted a histopathological evaluation via histological staining and immunostaining for glial fibrillary acidic protein and synaptophysin expression, both of which are markers of hepatic stellate cell (HSC) activation. Both ARS and repeated stress increased markers of hepatic cell injury, oxidative stress, and HSC activation. Blocking NMDA with memantine provided a hepatoprotective effect in acute and repeated restraint stress and decreased hepatic cell injury, oxidative stress, and HSC activation.
a Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Shaimaa Nasr
SN
Amin
b Quality Assurance Department, Hikma Pharmaceuticals, Cairo, Egypt.
Ahmed Amro
AA
El-Aidi
c Department of Histology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Maha Baligh
MB
Zickri
d Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.
Laila Ahmed
LA
Rashed
e Department of Anatomy, Faculty of Medicine, Cairo University, Cairo, Egypt.|f California University of Science and Medicine, School of Medicine, Department of Medical Education, Colton, CA, USA.
Sherif Sabry
SS
Hassan
D000818:Animals; D003094:Collagen / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012149:Restraint, Physical / Q000523:psychology*; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology*; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin; D003094:Collagen; D008559:Memantine
acute stress; contention; foie; liver; memantine; mémantine; repeated stress; restraint; stress aigu; stress répété