Impact of agmatine on cerebral astrocyte reactivity, neurodegeneration, and oxidative stress in bile duct-ligated rats.

Hepatic encephalopathy (HE) is a severe neurological disorder arising from liver disease, often studied using the bile duct ligation (BDL) model. This condition leads to cholestasis, triggering oxidative stress, liver damage, and fibrosis. Agmatine (AGM), an endogenous polyamine known for its neuroprotective effects, has shown potential in treating various neurological and psychological disorders due to its anti-inflammatory and antioxidant properties. This study investigates the potential of AGM to mitigate liver and brain injury in a rat model of BDL-induced HE. Adult male Wistar rats were divided into four groups: a Sham group, a BDL group, and two BDL + AGM groups (receiving 40 mg/kg and 80 mg/kg AGM, respectively). AGM was administered via oral gavage, starting from the second week post-surgery and continuing for four weeks. At the end of the study, the animals were sacrificed; brain and liver tissues, along with blood samples, were collected for analysis. Glial fibrillary acidic protein (GFAP) immunohistochemistry staining was performed to assess astrocyte reactivity. Brain oxidative stress, liver function, and fibrosis were assessed. The BDL animals exhibited significantly increased liver damage markers, liver tissue fibrosis, and brain oxidative stress markers. Astrogliosis was evident in the hippocampus of BDL rats. However, AGM treatment ameliorated these effects, improving superoxide dismutase (SOD) and Malonaldehyde (MDA) levels, and reducing liver dysfunction. AGM also reduced hippocampal astrogliosis and cerebellar Purkinje cell degeneration in BDL rats. These findings suggest that AGM holds potential as a therapeutic agent for mitigating liver and brain damage associated with hepatic encephalopathy.