Assessment of hepatic prostaglandin E2 level in carbamazepine induced liver injury.
Endocr Regul
; 56(1): 22-30, 2022 Feb 18.
Article
in En
| MEDLINE
| ID: mdl-35180822
ABSTRACT
Objective. Carbamazepine (CBZ), a widely used antiepileptic drug, is one major cause of the idiosyncratic liver injury along with immune reactions. Conversely, prostaglandin E2 (PGE2) demonstrates a hepatoprotective effect by regulating immune reactions and promoting liver repair in various types of liver injury. However, the amount of hepatic PGE2 during CBZ-induced liver injury remains elusive. In this study, we aimed to evaluate the hepatic PGE2 levels during CBZ-induced liver injury using a mouse model. Methods. Mice were orally administered with CBZ at a dose of 400 mg/kg for 4 days, and 800 mg/kg on the 5th day. Results. Plasma alanine transaminase (ALT) level increased in some of mice 24 h after the last CBZ administration. Although median value of hepatic PGE2 amount in the CBZ-treated mice showed same extent as vehicle-treated control mice, it exhibited significant elevated level in mice with severe liver injury presented by a plasma ALT level >1000 IU/L. According to these results, mice had a plasma ALT level >1000 IU/L were defined as responders and the others as non-responders in this study. Even though, the hepatic PGE2 levels increased in responders, the hepatic expression and enzyme activity related to PGE2 production were not upregulated when compared with vehicle-treated control mice. However, the hepatic 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression and activity decreased significantly in responders when compared with control mice. Conclusions. These results indicate that elevated hepatic PGE2 levels can be attributed to the downregulation of 15-PGDH expression under CBZ-induced liver injury.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chemical and Drug Induced Liver Injury
/
Chemical and Drug Induced Liver Injury, Chronic
Type of study:
Etiology_studies
Limits:
Humans
Language:
En
Journal:
Endocr Regul
Journal subject:
ENDOCRINOLOGIA
Year:
2022
Document type:
Article
Affiliation country:
Japón