Hepatic cytoprotection by prostaglandins: Theories unlimited
Article first published online: 5 DEC 2005
Copyright © 1988 American Association for the Study of Liver Diseases
Volume 8, Issue 4, pages 969–970, July/August 1988
How to Cite
Levine, R. A. (1988), Hepatic cytoprotection by prostaglandins: Theories unlimited. Hepatology, 8: 969–970. doi: 10.1002/hep.1840080443
- Issue published online: 5 DEC 2005
- Article first published online: 5 DEC 2005
16,16 Dimethyl prostaglandin E2 (dmPGE2), a known cytoprotective agent, was examined for its ability to alter the course of fulminant hepatitis in an experimental model of fulminant viral hepatitis, murine hepatitis virus type 3 (MHV-3). Fully susceptible BALB/cJ mice, infected with 100 50% lethal doses (LD50) of MHV-3 developed histologic and biochemical evidence of fulminant hepatitis, as evidenced by massive hepatic necrosis with hypoglycemia, metabolic acidosis, and a markedly elevated serum alanine aminotransferase (ALT) (mean, 1,402 ± 619 IU/liter). In contrast, animals treated with dmPGE2 either before or after infection (up to 48 h) demonstrated a marked reduction in both histologic and biochemical evidence of liver damage as characterized by normal blood glucose, total CO2, and ALT determinations (mean ALT, 63 ± 40 IU/liter). Treatment of infected mice with PGF2 demonstrated no cytoprotective effects. High titers of infectious virus were recovered from the livers of both dmPGE2-treated and -untreated animals throughout the course of infection.
In a parallel in vitro study, dmPGE2 (10−4–10−8 M) demonstrated a similar cytoprotective effect on monolayers of isolated cultured hepatocytes from fully susceptible BALB/cJ mice infected at a multiplicity of infection of 0.1, 1.0, and 10.0. In addition, splenic macrophages recovered from infected and untreated BALB/cJ mice demonstrated a marked augmentation in procoagulant activity (PCA) from a basal 10 ± 5 mU/106 splenic macrophages to a maximum of 615 ± 102 mU/106 splenic macrophages, whereas no increase in macrophage PCA was detected in infected animals treated with dmPGE2. These results suggest that dmPGE2, without detectably altering viral replication or infectivity in vivo, confers a marked cytoprotective effect on hepatocytes both in vivo and in vitro, and prevents the induction of macrophage PCA in vivo in fully susceptible BALB/cJ mice after murine hepatitis virus type 3 infection.