Tumor necrosis factor is a terminal mediator in galactosamine/endotoxin-induced hepatitis in mice - PubMed (original) (raw)

Tumor necrosis factor is a terminal mediator in galactosamine/endotoxin-induced hepatitis in mice

G Tiegs et al. Biochem Pharmacol. 1989.

Abstract

Intravenous injection of murine recombinant tumor necrosis factor alpha(TNF-alpha) to male NMRI albino mice in doses greater than 4 micrograms/kg (specific activity 4 x 10(7) U/mg) resulted in a fulminant hepatitis when animals had been sensitized 1 hr before by intraperitoneal administration of 700 mg/kg galactosamine. Liver injury was assessed by measurement of serum transaminases as well as sorbitol dehydrogenase activity 8 hr after administration of TNF-alpha. Pretreatment with either galactosamine or 40 micrograms/kg TNF-alpha alone did not cause hepatitis. Pretreatment of galactosamine/TNF-alpha-injured mice with 800 mg/kg uridine or with 6 mg/kg calmidazolium fully protected the animals, while administration of either verapamil or nifedipine (100 mg/kg, respectively) had no significant effect. The following inhibitors of generation or action of leukotriene D4, which were previously shown to block galactosamine/endotoxin-induced hepatitis in mice, failed to protect against galactosamine/TNF-alpha-induced intoxication: 200 micrograms/kg dexamethasone, 174 mg/kg BW 755 C or 13 x 10 mg/kg FPL 55712. In addition, unlike in the galactosamine/endotoxin model no prevention was achieved by pretreatment of galactosamine/TNF-alpha-injured animals with the following substances blocking the development of an ischemia/reperfusion syndrome: 2 x 100 mg/kg allopurinol, 3.3 x 10(4) U/kg superoxide dismutase, 10(6) U/kg catalase or 10 micrograms/kg iloprost. We conclude from our results that tumor necrosis factor alpha is likely to act as a final mediator of endotoxin action in a sequence of events which includes formation of leukotriene D4 and reactive oxygen species.

PubMed Disclaimer

Cited by

The inhibitory effects of allopurinol on the production and cytotoxicity of tumor necrosis factor.
Oláh T, Régely K, Mándi Y. Oláh T, et al. Naunyn Schmiedebergs Arch Pharmacol. 1994 Jul;350(1):96-9. doi: 10.1007/BF00180017. Naunyn Schmiedebergs Arch Pharmacol. 1994. PMID: 7935861
RIPK1 protects from TNF-α-mediated liver damage during hepatitis.
Filliol A, Piquet-Pellorce C, Le Seyec J, Farooq M, Genet V, Lucas-Clerc C, Bertin J, Gough PJ, Dimanche-Boitrel MT, Vandenabeele P, Bertrand MJ, Samson M. Filliol A, et al. Cell Death Dis. 2016 Nov 10;7(11):e2462. doi: 10.1038/cddis.2016.362. Cell Death Dis. 2016. PMID: 27831558 Free PMC article.
Dibenzazepine combats acute liver injury in rats via amendments of Notch signaling and activation of autophagy.
Ahmed LA, Abd El-Rhman RH, Gad AM, Hassaneen SK, El-Yamany MF. Ahmed LA, et al. Naunyn Schmiedebergs Arch Pharmacol. 2021 Feb;394(2):337-348. doi: 10.1007/s00210-020-01977-0. Epub 2020 Sep 28. Naunyn Schmiedebergs Arch Pharmacol. 2021. PMID: 32984915
Colchicine prevents tumor necrosis factor-induced toxicity in vivo.
Tiegs G, Freudenberg MA, Galanos C, Wendel A. Tiegs G, et al. Infect Immun. 1992 May;60(5):1941-5. doi: 10.1128/iai.60.5.1941-1945.1992. Infect Immun. 1992. PMID: 1563785 Free PMC article.
The effect of lipopolysaccharide, interleukin-1 and tumour necrosis factor on the hepatic accumulation of 5-hydroxytryptamine and platelets in the mouse.
Endo Y, Nakamura M. Endo Y, et al. Br J Pharmacol. 1992 Mar;105(3):613-9. doi: 10.1111/j.1476-5381.1992.tb09028.x. Br J Pharmacol. 1992. PMID: 1628148 Free PMC article.

Tumor necrosis factor is a terminal mediator in galactosamine/endotoxin-induced hepatitis in mice - PubMed (original) (raw)