Tumor necrosis factor-alpha-null mice are not resistant to cadmium chloride-induced hepatotoxicity

Toxicology and Applied Pharmacology
Eric B Harstad, C D Klaassen

Abstract

Acute administration of cadmium results in hepatotoxicity. Recent reports indicate that Kupffer cells, the resident macrophages of the liver, participate in the manifestation of chemical-induced hepatotoxicity. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that is a major product of Kupffer cells and mediates the hepatotoxic effects of lipopolysaccharide (LPS). It has been speculated that cadmium also may exert its hepatotoxicity via the production of TNF-alpha by the Kupffer cells. Therefore, this study was undertaken to determine whether mice deficient in TNF-alpha are resistant to Cd-induced hepatotoxicity. TNF-alpha-null (TNF-KO) and wild-type (WT) mice were dosed ip with saline, LPS (0.1 mg/kg)/Gln (d-galactosamine, 700 mg/kg), or CdCl2 (2.2, 2.8, 3.4, and 3.9 mg Cd/kg). Serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities were quantified to assess liver injury. Caspase-3 activity was quantified to assess hepatocellular apoptosis. LPS/Gln treatment increased ALT (17-fold) and SDH (21-fold) in WT mice. In contrast, LPS/Gln-treatment did not significantly increase ALT or SDH in TNF-KO mice. LPS/Gln-treatment caused a 7.8-fold increase in caspase-3 activity in WT mice but di...Continue Reading

References

Apr 1, 1992·Archives of Biochemistry and Biophysics·G M Adamson, R E Billings
May 1, 1980·Toxicology and Applied Pharmacology·N H StaceyC D Klaassen
Dec 1, 1983·Toxicology and Applied Pharmacology·M J Harvey, C D Klaassen
Sep 15, 1982·Toxicology and Applied Pharmacology·R E DudleyC Klaassen
Jul 1, 1995·Toxicology and Applied Pharmacology·M E BlazkaM I Luster
Apr 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·D L LaskinD J Jollow
Jun 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·N A EssaniH Jaeschke
Sep 10, 1993·Cell·L A TartagliaD V Goeddel
Aug 1, 1996·Toxicology and Applied Pharmacology·H JaeschkeR A Roth
Jan 1, 1996·Toxicologic Pathology·D L Laskin
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·M W MarinoL J Old
Dec 24, 1997·Brain Research. Molecular Brain Research·F GillardonK A Hossmann
Apr 16, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·F BoessU A Boelsterli
May 8, 1998·Toxicology and Applied Pharmacology·S S HabeebuC D Klaassen
Jul 1, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·S L MichaelJ A Hinson
Jul 10, 1999·Mechanisms of Ageing and Development·L E RikansT Yamano

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Citations

Aug 4, 2009·Chemical Research in Toxicology·Debra L Laskin
May 27, 2006·Journal of Toxicology and Environmental Health. Part a·Jiyoung Kim, Raghubir P Sharma
Aug 31, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Shunchang WangLijun Wu
Apr 4, 2013·The American Journal of Chinese Medicine·Su-Jin KimSeung-Heon Hong
Jun 16, 2009·Journal of Inflammation·Subhadip KunduArindam Bhattacharyya
Jul 17, 2008·Environmental Health Perspectives·Su-Jin KimSeung-Heon Hong
Jul 21, 2007·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Neelima Pathak, Shashi Khandelwal
Oct 21, 2006·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Wei-Ping MaoTing Tian
Jul 1, 2006·Toxicology in Vitro : an International Journal Published in Association with BIBRA·T N D PhamC Jumarie
Jan 18, 2006·Toxicology·Neelima Pathak, Shashi Khandelwal
May 21, 2011·The American Journal of Chinese Medicine·Su-Jin KimSeung-Heon Hong
Dec 17, 2011·Toxicology and Industrial Health·Loukas G KyriakouGeorgios I Panoutsopoulos
Sep 30, 2010·Human & Experimental Toxicology·W P MaoZ J He
Jan 27, 2004·Journal of Cellular Biochemistry·Chwen-Ming ShihChien-Tsu Chen
Apr 22, 2003·Journal of Cellular Biochemistry·Chwen-Ming ShihChien-Tsu Chen
Jun 21, 2005·Annals of the New York Academy of Sciences·Yung-Luen ShihChwen-Ming Shih
Jan 15, 2013·Journal of Biochemical and Molecular Toxicology·Neelima PathakShashi Khandelwal
Nov 20, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chang HanTong Wu

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