Alpha-Mangostin Partially Preserves Expression of Ammonia-Metabolizing Enzymes in Thioacetamide- Induced Fibrotic and Cirrhotic Rats
Montinee Khunvirojpanich MSc*, Udomsri Showpittapornchai PhD**, Primchanien Moongkarndi PhD***, Wisuit Pradidarcheep PhD**
Affiliation : * Department of Science, Biomedical Sciences, Mahidol University International College, Nakhon Pathom, Thailand ** Department of Anatomy, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand *** Department of Microbiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand
Background : Ammonia metabolizing enzymes, carbamyol phosphate synthetase (CPS) and glutamine synthetase (GS), are
expressed in the periportal and pericentral hepatocytes, respectively. CPS and GS function complementary to ensure complete
ammonia detoxification. Immunohistochemical analysis confirmed the decline of both CPS and GS in cirrhotic rat liver
induced by thioacetamide (TAA). Alpha-mangostin (AM), a major derivative of xanthone from mangosteen, has been reported
to possess a wide range of pharmacological properties.
Objective : To examine the preventive effects of AM on CPS and GS expression in fibrotic and cirrhotic rats induced by TAA
over sixteen weeks.
Material and Method: Twenty-four male Wistar rats were divided into 4 groups of 6 animals each. Group 1 was for control.
Group 2 was for pure TAA treatment. Group 3 was for pure AM administration. Group 4, prevention group, was concurrently
treated with TAA and AM. Immunohistochemical technique was employed in order to elucidate the expression of CPS and GS
in each animal group.
Results : Immunohistochemical staining for CPS and GS showed an increasing decline from week eight to sixteen under pure-
TAA condition. Fibrous bridgings, nodule formations, and regenerative nodules were detected. Pure-AM condition yielded
strongly CPS and GS-stained hepatocytes in a fashion similar to the control. Results from the prevention group showed a
decreasing decline of CPS and GS immuno-reactivity from week eight to sixteen as compared to pure-TAA condition. Fewer
fibrous portal-caval bridgings were observed at week eight and CPS-positive hepatocytes were found in continuous rings.
Conclusion : Alpha-mangostin could partially preserve the normal expression of ammonia-metabolizing enzymes under
TAA-induced fibrotic and cirrhotic conditions.
Keywords : Cirrhosis, Glutamine synthetase, Carbamoyl phosphate synthetase, Thioacetamide, Alpha-mangostin
