Tags

Type your tag names separated by a space and hit enter

Etoposide prevents apoptosis in mouse liver with D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure resulting in reduction of lethality.
Hepatology 2001; 33(6):1441-50Hep

Abstract

D-Galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury is an experimental model of fulminant hepatic failure in which tumor necrosis factor alpha (TNF-alpha) plays a pivotal role. We examined the effects of etoposide on GalN/LPS-induced fulminant hepatic failure. Mice were given an intraperitoneal dose of GalN (800 microg/g body weight)/LPS (100 ng/g body weight) with and without intraperitoneal etoposide (10 microg/g body weight) treatment. Liver injury was assessed biochemically and histologically. TNF-alpha levels in the serum, and apoptosis of hepatocytes and CPP32/caspase-3 in the liver, were determined. GalN/LPS treatment caused lethal liver injury in 87% of animals (13 of 15). The effect was associated with significant increases in TNF-alpha and alanine transaminase (ALT) levels in serum, the number of apoptotic hepatocytes, CPP32/caspase-3 activity, and TNF receptor 1 (TNFR1) mRNA expression in the liver. Etoposide (10 microg/g body weight) was given 3 times (at 50, 26, and 4 hours before GalN/LPS administration). Treatment of GalN/LPS-treated mice with etoposide reduced apoptosis of hepatocytes, resulting in reduction of lethality (13% [2 of 15]), while another topoisomerase II inhibitor, IRCF-193, showed no significant effect. The antilethal effect of etoposide was also confirmed in GalN/TNF-alpha-induced fulminant hepatic failure. Etoposide treatment reduced CPP32/caspase-3 activity in the liver, although it did not alter the serum TNF-alpha levels or hepatic TNFR1 mRNA expressions. In addition, etoposide treatment enhanced the mRNA and protein expression of Bcl-xL, an antiapoptotic molecule in the liver. The present findings suggest that etoposide prevents endotoxin-induced lethal liver injury by up-regulation of Bcl-xL, and that etoposide could be useful for the treatment of TNF-alpha-mediated liver diseases.

Authors+Show Affiliations

Department of Internal Medicine II, Miyazaki Medical College, Miyazaki, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11391533

Citation

Nakama, T, et al. "Etoposide Prevents Apoptosis in Mouse Liver With D-galactosamine/lipopolysaccharide-induced Fulminant Hepatic Failure Resulting in Reduction of Lethality." Hepatology (Baltimore, Md.), vol. 33, no. 6, 2001, pp. 1441-50.
Nakama T, Hirono S, Moriuchi A, et al. Etoposide prevents apoptosis in mouse liver with D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure resulting in reduction of lethality. Hepatology. 2001;33(6):1441-50.
Nakama, T., Hirono, S., Moriuchi, A., Hasuike, S., Nagata, K., Hori, T., ... Tsubouchi, H. (2001). Etoposide prevents apoptosis in mouse liver with D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure resulting in reduction of lethality. Hepatology (Baltimore, Md.), 33(6), pp. 1441-50.
Nakama T, et al. Etoposide Prevents Apoptosis in Mouse Liver With D-galactosamine/lipopolysaccharide-induced Fulminant Hepatic Failure Resulting in Reduction of Lethality. Hepatology. 2001;33(6):1441-50. PubMed PMID: 11391533.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Etoposide prevents apoptosis in mouse liver with D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure resulting in reduction of lethality. AU - Nakama,T, AU - Hirono,S, AU - Moriuchi,A, AU - Hasuike,S, AU - Nagata,K, AU - Hori,T, AU - Ido,A, AU - Hayashi,K, AU - Tsubouchi,H, PY - 2001/6/8/pubmed PY - 2001/6/29/medline PY - 2001/6/8/entrez SP - 1441 EP - 50 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 33 IS - 6 N2 - D-Galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury is an experimental model of fulminant hepatic failure in which tumor necrosis factor alpha (TNF-alpha) plays a pivotal role. We examined the effects of etoposide on GalN/LPS-induced fulminant hepatic failure. Mice were given an intraperitoneal dose of GalN (800 microg/g body weight)/LPS (100 ng/g body weight) with and without intraperitoneal etoposide (10 microg/g body weight) treatment. Liver injury was assessed biochemically and histologically. TNF-alpha levels in the serum, and apoptosis of hepatocytes and CPP32/caspase-3 in the liver, were determined. GalN/LPS treatment caused lethal liver injury in 87% of animals (13 of 15). The effect was associated with significant increases in TNF-alpha and alanine transaminase (ALT) levels in serum, the number of apoptotic hepatocytes, CPP32/caspase-3 activity, and TNF receptor 1 (TNFR1) mRNA expression in the liver. Etoposide (10 microg/g body weight) was given 3 times (at 50, 26, and 4 hours before GalN/LPS administration). Treatment of GalN/LPS-treated mice with etoposide reduced apoptosis of hepatocytes, resulting in reduction of lethality (13% [2 of 15]), while another topoisomerase II inhibitor, IRCF-193, showed no significant effect. The antilethal effect of etoposide was also confirmed in GalN/TNF-alpha-induced fulminant hepatic failure. Etoposide treatment reduced CPP32/caspase-3 activity in the liver, although it did not alter the serum TNF-alpha levels or hepatic TNFR1 mRNA expressions. In addition, etoposide treatment enhanced the mRNA and protein expression of Bcl-xL, an antiapoptotic molecule in the liver. The present findings suggest that etoposide prevents endotoxin-induced lethal liver injury by up-regulation of Bcl-xL, and that etoposide could be useful for the treatment of TNF-alpha-mediated liver diseases. SN - 0270-9139 UR - https://www.unboundmedicine.com/medline/citation/11391533/Etoposide_prevents_apoptosis_in_mouse_liver_with_D_galactosamine/lipopolysaccharide_induced_fulminant_hepatic_failure_resulting_in_reduction_of_lethality_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0270-9139(01)00020-9 DB - PRIME DP - Unbound Medicine ER -