Increase of the brain uptake index for L-ornithine in rats with hepatic encephalopathy

We measured the brain uptake index (BUI) for radiolabelled L-ornithine (ORN) in rats with acute hepatic encephalopathy (HE) induced by two (onset stage) or three (comatous stage) administrations of a hepatotoxin-thioacetamide (TAA). In the comatose group, an increase of the BUI to 275% of control was measured at 24 h post-treatment. In the onset group, the BUI for ORN increased gradually with time: it reached 220% of control at 7 days post-treatment and 442% of control at 21 days post-treatment. HE did not raise the BUI for a blood-brain barrier (BBB) non-penetrable amino acid L-aspartate (ASP), indicating that HE activates ORN transport but does not produce BBB leakage. ORN transport through BBB was not increased in rats with hyperammonemia comparable to that accompanying HE, but was induced without liver damage. Considering recent evidence that ORN acting intracerebrally ameliorates pathophysiological symptoms of HE, increased transport ORN across BBB should facilitate HE therapy based on systemic administration of this amino acid.