Hyperammonaemia induces mitochondrial dysfunction and neuronal cell death.

ABSTRACT:

Background & aims

In cirrhosis, astrocytic swelling is believed to be the principal mechanism of ammonia neurotoxicity leading to hepatic encephalopathy (HE). The role of neuronal dysfunction in HE is not clear. We aimed to explore the impact of hyperammonaemia on mitochondrial function in primary co-cultures of neurons and astrocytes and in acute brain slices of cirrhotic rats using live cell imaging.

Methods

To primary cocultures of astrocytes and neurons, low concentrations (1 and 5 μM) of NH₄Cl were applied. In rats with bile duct ligation (BDL)-induced cirrhosis, a model known to induce hyperammonaemia and minimal HE, acute brain slices were studied. One group of BDL rats was treated twice daily with the ammonia scavenger ornithine phenylacetate (OP; 0.3 g/kg

SUBMITTER: Angelova PR 

PROVIDER: S-EPMC9278080 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature