Ammonia increases RNA oxidation in cultured astrocytes and brain in vivo

Oxidative stress plays a major role in cerebral ammonia toxicity and the pathogenesis of hepatic encephalopathy (HE) but the mechanisms leading to impaired protein function are still not fully understood. Here we show that ammonia induces a rapid RNA oxidation in cultured rat astrocytes, vital mouse brain slices and rat brain in vivo. Also hypoosmolarity increased RNA oxidation in cultured astrocytes, indicating that astrocyte swelling is a potential trigger. Amongst the oxidized RNA species the 18S-rRNA and the mRNA coding for the glutamate/aspartate transporter (GLAST), but not the abundant β-actin mRNA were i…