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Differential effects of pyrrolidine dithiocarbamate on TNF-alpha-mediated liver injury in two different models of fulminant hepatitis.
J Hepatol. 2008 Mar; 48(3):442-52.JH

Abstract

BACKGROUND/AIMS

Pyrrolidine dithiocarbamate (PDTC) is an inhibitor of nuclear factor kappa B (NF-kappaB) activation. The present study aimed to investigate the effects of PDTC on lipopolysaccharide (LPS)-induced liver injury in two different models of fulminant hepatitis.

METHODS

Mice infected with Bacillus Calmette Guerin (BCG) were challenged with LPS (0.2 mg/kg) to induce the model of inflammatory liver injury. Mice were injected with D-galactosamine (GalN, 600 mg/kg) and LPS (20 microg/kg) to induce the model of apoptotic liver injury. In the treatment groups, mice were pre-treated with PDTC (100 mg/kg), initiated 24 h prior to LPS.

RESULTS

PDTC pretreatment reduced the infiltration of inflammatory cells, inhibited NF-kappaB activation and the expression of tumor necrosis factor alpha (TNF-alpha), attenuated nitric oxide production, and alleviated hepatic glutathione depletion. Correspondingly, PDTC reduced serum alanine aminotransferase, improved hepatic necrosis, and prolonged the survival in the BCG/LPS model. Conversely, PDTC accelerated death and aggravated liver apoptosis in the GalN/LPS model, although it reduced nitric oxide production, attenuated glutathione depletion, and inhibited the expression of TNF-alpha in liver.

CONCLUSIONS

PDTC protects mice against BCG/LPS-induced inflammatory liver injury through the repression of NF-kappaB-mediated TNF-alpha release, while it seems to be detrimental in GalN/LPS-induced apoptotic liver damage.

Authors+Show Affiliations

Department of Toxicology, Anhui Medical University, Hefei, China.No affiliation info availableNo affiliation info availableNo 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)

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

Language

eng

PubMed ID

18215436

Citation

Lu, Jin-Wei, et al. "Differential Effects of Pyrrolidine Dithiocarbamate On TNF-alpha-mediated Liver Injury in Two Different Models of Fulminant Hepatitis." Journal of Hepatology, vol. 48, no. 3, 2008, pp. 442-52.
Lu JW, Wang H, Yan-Li J, et al. Differential effects of pyrrolidine dithiocarbamate on TNF-alpha-mediated liver injury in two different models of fulminant hepatitis. J Hepatol. 2008;48(3):442-52.
Lu, J. W., Wang, H., Yan-Li, J., Zhang, C., Ning, H., Li, X. Y., Zhang, H., Duan, Z. H., Zhao, L., Wei, W., & Xu, D. X. (2008). Differential effects of pyrrolidine dithiocarbamate on TNF-alpha-mediated liver injury in two different models of fulminant hepatitis. Journal of Hepatology, 48(3), 442-52. https://doi.org/10.1016/j.jhep.2007.10.014
Lu JW, et al. Differential Effects of Pyrrolidine Dithiocarbamate On TNF-alpha-mediated Liver Injury in Two Different Models of Fulminant Hepatitis. J Hepatol. 2008;48(3):442-52. PubMed PMID: 18215436.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential effects of pyrrolidine dithiocarbamate on TNF-alpha-mediated liver injury in two different models of fulminant hepatitis. AU - Lu,Jin-Wei, AU - Wang,Hua, AU - Yan-Li,Ji, AU - Zhang,Cheng, AU - Ning,Huan, AU - Li,Xiang-Yun, AU - Zhang,Heng, AU - Duan,Zi-Hao, AU - Zhao,Lei, AU - Wei,Wei, AU - Xu,De-Xiang, Y1 - 2008/01/14/ PY - 2007/09/09/received PY - 2007/10/10/revised PY - 2007/10/25/accepted PY - 2008/1/25/pubmed PY - 2008/6/20/medline PY - 2008/1/25/entrez SP - 442 EP - 52 JF - Journal of hepatology JO - J Hepatol VL - 48 IS - 3 N2 - BACKGROUND/AIMS: Pyrrolidine dithiocarbamate (PDTC) is an inhibitor of nuclear factor kappa B (NF-kappaB) activation. The present study aimed to investigate the effects of PDTC on lipopolysaccharide (LPS)-induced liver injury in two different models of fulminant hepatitis. METHODS: Mice infected with Bacillus Calmette Guerin (BCG) were challenged with LPS (0.2 mg/kg) to induce the model of inflammatory liver injury. Mice were injected with D-galactosamine (GalN, 600 mg/kg) and LPS (20 microg/kg) to induce the model of apoptotic liver injury. In the treatment groups, mice were pre-treated with PDTC (100 mg/kg), initiated 24 h prior to LPS. RESULTS: PDTC pretreatment reduced the infiltration of inflammatory cells, inhibited NF-kappaB activation and the expression of tumor necrosis factor alpha (TNF-alpha), attenuated nitric oxide production, and alleviated hepatic glutathione depletion. Correspondingly, PDTC reduced serum alanine aminotransferase, improved hepatic necrosis, and prolonged the survival in the BCG/LPS model. Conversely, PDTC accelerated death and aggravated liver apoptosis in the GalN/LPS model, although it reduced nitric oxide production, attenuated glutathione depletion, and inhibited the expression of TNF-alpha in liver. CONCLUSIONS: PDTC protects mice against BCG/LPS-induced inflammatory liver injury through the repression of NF-kappaB-mediated TNF-alpha release, while it seems to be detrimental in GalN/LPS-induced apoptotic liver damage. SN - 0168-8278 UR - https://www.unboundmedicine.com/medline/citation/18215436/Differential_effects_of_pyrrolidine_dithiocarbamate_on_TNF_alpha_mediated_liver_injury_in_two_different_models_of_fulminant_hepatitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8278(07)00655-1 DB - PRIME DP - Unbound Medicine ER -