Potential role of caveolin-1 in acetaminophen-induced hepatotoxicity.

Toxicology and Applied Pharmacology
Carol R GardnerD L Laskin

Abstract

Caveolin-1 (Cav-1) is a membrane scaffolding protein, which functions to regulate intracellular compartmentalization of various signaling molecules. In the present studies, transgenic mice with a targeted disruption of the Cav-1 gene (Cav-1(-/-)) were used to assess the role of Cav-1 in acetaminophen-induced hepatotoxicity. Treatment of wild-type mice with acetaminophen (300 mg/kg) resulted in centrilobular hepatic necrosis and increases in serum transaminases. This was correlated with decreased expression of Cav-1 in the liver. Acetaminophen-induced hepatotoxicity was significantly attenuated in Cav-1(-/-) mice, an effect that was independent of acetaminophen metabolism. Acetaminophen administration resulted in increased hepatic expression of the oxidative stress marker, lipocalin 24p3, as well as hemeoxygenase-1, but decreased glutathione and superoxide dismutase-1; no differences were noted between the genotypes suggesting that reduced toxicity in Cav-1(-/-) mice is not due to alterations in antioxidant defense. In wild-type mice, acetaminophen increased mRNA expression of the pro-inflammatory cytokines, interleukin-1beta, and monocyte chemoattractant protein-1 (MCP-1), as well as cyclooxygenase-2, while 15-lipoxygenase (15-...Continue Reading

Citations

Sep 17, 2013·Journal of Physiology and Biochemistry·Dina S El-AgamyNareman M Gamil
Oct 5, 2010·Annual Review of Pharmacology and Toxicology·Debra L LaskinJeffrey D Laskin
May 11, 2010·Journal of Leukocyte Biology·Debra L LaskinJeffrey D Laskin
Nov 4, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Carol R GardnerDebra L Laskin
Nov 17, 2011·BMC Gastroenterology·Runkuan YangJyrki Tenhunen
Mar 31, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ana-Cristina DragomirDebra L Laskin
Sep 25, 2012·Experimental and Molecular Pathology·Agnieszka J ConnorDebra L Laskin
Apr 26, 2011·Toxicology and Applied Pharmacology·Ana-Cristina DragomirDebra L Laskin
Mar 8, 2014·Molecular Medicine Reports·Kun-Peng WangJin-Zhen Zhang

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