Agmatine (decarboxylated arginine), a modulator of liver cell homeostasis and proliferation

Agmatine interferes with polyamine metabolism and cell growth in cell culture. When absorbed from the gastrointestinal tract, it is accumulated in the liver. Based on these facts, the aim of the present study was to investigate the effects of agmatine on the proliferation of rat and human hepatoma cells and on regeneration of rat liver after partial two-thirds hepatectomy. In cultured cells of the rat and human hepatoma cell lines McRH7777 and HepG2 respectively, agmatine reduced ATP and protein contents (50% inhibition in the range of 169-569 microM) which were determined as estimates for the cell number. This antiproliferative action was not due to an effect on ornithine decarboxylase antizyme, since its intracellular concentration was not significantly changed by agmatine. In addition, agmatine metabolism by diamine oxidase seems not to be involved in the inhibition of cell growth and proliferation because the diamine oxidase inhibitor aminoguanidine did not alter agmatine's antiproliferative action. After two-thirds hepatectomy, daily administration of 250 mg and 500 mg agmatine to rats for 6 days by gavage reduced the weight gain of the remnant liver on day 7 by 19.5+/-0.9% and 22.3+/-1.5% respectively. The decrease in regeneration correlated with a pronounced accumulation of agmatine in the liver. Hence, the present data provide evidence of an involvement of agmatine in liver cell growth.