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