Serum DNA polymerase β as an indicator for fatal liver injury of rat induced by d-galactosamine hydrochloride and lipopolysaccharide

• Published in: Biochimica et biophysica acta Vol. 1380; no. 3; pp. 369 - 376
• Main Authors: Kato, Osamu, Fukuda, Yoshihide, Hayakawa, Tetsuo, Izuta, Shunji, Yoshida, Shonen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 08.05.1998
• Subjects: Alanine Transaminase - blood; Animals; Biomarkers - blood; d-Galactosamine hydrochloride; DNA Polymerase beta - blood; DNA polymerase β; Dose-Response Relationship, Drug; Galactosamine - toxicity; Hepatic Encephalopathy - blood; Hepatic Encephalopathy - chemically induced; Hepatic Encephalopathy - enzymology; Hepatic failure; Lipopolysaccharide; Lipopolysaccharides - toxicity; Liver - enzymology; Liver - pathology; Male; Predictive Value of Tests; Prognosis; Rats; Rats, Wistar; Serum aminotransferase; Time Factors; Hepatic failure; Lipopolysaccharide; d-Galactosamine hydrochloride; DNA polymerase β; Serum aminotransferase
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/S0304-4165(98)00008-7

DNA polymerase β (pol β) is a nuclear enzyme that is tightly bound to chromatin. Release of the pol β activity into serum, therefore, may indicate the occurrence of massive destruction of cell nuclei in organs or tissues. In the present study, we made a liver injury model rat by the intraperitoneal injection of d-galactosamine hydrochloride (GalN, 500 mg/kg) and lipopolysaccharide (LPS, 100 μg/kg). Serum from the GalN/LPS-treated rats showed a high level of pol β activity up to 118 pmol/0.5 μl serum (4700 cpm) at 12 h after the treatment, while the control rat serum showed the back ground level (3.8 pmol/0.5 μl, 150±70 cpm). The serum pol β activity was sensitive to inhibition by 2′,3′-dideoxyTTP and by an anti-rat pol β antibody. Among 30 rats treated with GalN/LPS, 10 rats died within 120 h (dead group). Serum pol β activity in the dead group was as high as 23.0±19.5 pmol/0.5 μl (925±778 cpm) at 10 h after the treatment, while in alive group ( n=20), it was 3.7±3.2 pmol. Levels of the serum pol β activity correlated well with the prognosis of GalN/LPS-treated rats based on an analysis of the receiver-operator characteristic curves.