Effect of lipopolysaccharide on in vivo and genetic regulation of rat urea synthesis


Dr. Susanne Schouw Nielsen, Department of Medicine V, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark
Tel: +45 89 493 897
Fax: +45 89 492 740
e-mail: schouw@akhphd.au.dk


Abstract: Background: The acute phase response causes a negative nitrogen balance. It is unknown whether this involves regulation of hepatic urea synthesis.

Methods: We examined the in vivo capacity of urea nitrogen synthesis (CUNS), mRNA levels of urea cycle enzyme genes and galactose elimination capacity (GEC) during moderate and severe acute phase response induced by low- and high-dose lipopolysaccharide (LPS) in rats.

Results: Low-dose LPS doubled CUNS (P<0.05), decreased the mRNA level of the rate-limiting urea cycle enzyme (arginino succinate synthetase (ASS) by 26% (P<0.05) and did not change GEC. High-dose LPS did not change CUNS, decreased the mRNA level of the flux-generating enzyme carbamoyl phosphate synthetase (CPS) by 11% (P<0.05) and the rate-limiting urea cycle enzyme (ASS) by 27% (P<0.05) and almost halved GEC (P<0.05).

Conclusion: The moderate acute phase response up-regulated in vivo urea synthesis but had the opposite effect on gene level. The severe acute phase response decreased the functional liver mass that attenuated the increase in urea synthesis.