P: 73 Acetate Attenuates the Astrocyte Swelling and Brain Edema in Severe Liver Failure

Abstract

BACKGROUND: Astrocyte swelling and brain edema are major complications of severe liver failure. Ammonia plays a major role in the development of astrocyte swelling/brain edema in this condition. However, current therapies have not thus far improved the outcome of liver failure induced astrocyte swelling/brain edema. Since acetate has been shown to have neuroprotective effect in other neurological conditions, likely though increased energy production, we examined whether acetate similarly protect cell swelling in cultured astrocytes post-ammonia exposure. We also examined whether treatment of rats with glyceryl triacetate (GTA), an acetate precursor, which is known to increase circulating, as well as tissue levels of acetate, alleviates the brain edema induced by the liver toxin thioacetamide (TAA). METHODS: Astrocyte cell volume was estimated by measuring the intracellular water space using 3-O-methylglucose. Brain water content was measured by using the gravimetric method. RESULTS: Exposure of astrocyte cultures to pathological concentrations of ammonia (NH4Cl; 5 mM) for 24 h significantly increased cell swelling. Co-treatment of ammonia with acetate reduced such swelling in a dose-dependent manner. Further, treatment of rats with TAA (250 mg/kg bw) for 3 days increased the brain water content, and that pretreatment of (intragastrically) TAA-treated rats with GTA (7.5 g/kg bw), attenuated brain edema. CONCLUSIONS: These findings strongly suggest that acetate supplementation will exert salutary effects in reducing brain edema in patients with severe liver failure.