BACKGROUND: The ratio of ornithine carbamoyltransferase (OCT) to alanine aminotransferase (ALT) or glutamate dehydrogenase (GDH) in serum has been suggested as an indicator for the diagnosis of hepatocellular carcinoma and alcoholic liver disease, respectively. However, the mechanisms responsible for the increase in these ratios are still unclear. METHODS: Wistar rats were pretreated with lipopolysaccharide (LPS) or gadolinium chloride (GD) before being administered with thioacetamide (TAA, 200 mg/kg, ip). Serum OCT and ALT levels were compared with control values. Half-lives of the enzymes in circulation were evaluated after the intravenous injection of the purified enzymes into rats with or without the pretreatment. RESULTS: The serum level of OCT at 24 h after the administration of TAA was significantly lower in the LPS-treated group, and not influenced by pretreatment with GD. The half-life of OCT was prolonged from 1.06+/-0.14 to 2.07+/-0.29 h (p<0.05) by the pretreatment with GD, but not influenced by the administration of LPS. No change was observed in the clearance of GDH or ALT among the pretreatments. CONCLUSIONS: Leakage into and clearance from the circulation of OCT are influenced by whether Kupffer cells are activated or not. OCT alone or in combination with other markers may be a useful indicator for Kupffer cell activation as well as mitochondrial damage in hepatic cells.
BACKGROUND: The ratio of ornithine carbamoyltransferase (OCT) to alanine aminotransferase (ALT) or glutamate dehydrogenase (GDH) in serum has been suggested as an indicator for the diagnosis of hepatocellular carcinoma and alcoholic liver disease, respectively. However, the mechanisms responsible for the increase in these ratios are still unclear. METHODS:Wistar rats were pretreated with lipopolysaccharide (LPS) or gadolinium chloride (GD) before being administered with thioacetamide (TAA, 200 mg/kg, ip). Serum OCT and ALT levels were compared with control values. Half-lives of the enzymes in circulation were evaluated after the intravenous injection of the purified enzymes into rats with or without the pretreatment. RESULTS: The serum level of OCT at 24 h after the administration of TAA was significantly lower in the LPS-treated group, and not influenced by pretreatment with GD. The half-life of OCT was prolonged from 1.06+/-0.14 to 2.07+/-0.29 h (p<0.05) by the pretreatment with GD, but not influenced by the administration of LPS. No change was observed in the clearance of GDH or ALT among the pretreatments. CONCLUSIONS: Leakage into and clearance from the circulation of OCT are influenced by whether Kupffer cells are activated or not. OCT alone or in combination with other markers may be a useful indicator for Kupffer cell activation as well as mitochondrial damage in hepatic cells.
Authors: D M Longo; G T Generaux; B A Howell; S Q Siler; D J Antoine; D Button; A Caggiano; A Eisen; J Iaci; R Stanulis; T Parry; M Mosedale; P B Watkins Journal: Clin Pharmacol Ther Date: 2017-05-27 Impact factor: 6.875