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Gap junction dysfunction reduces acetaminophen hepatotoxicity with impact on apoptotic signaling and connexin 43 protein induction in rat.
- Source :
-
Toxicologic pathology [Toxicol Pathol] 2010 Feb; Vol. 38 (2), pp. 280-6. Date of Electronic Publication: 2010 Jan 22. - Publication Year :
- 2010
-
Abstract
- Acetaminophen (APAP) is a widely used antipyretic and analgesic agent. However, overdosing and sometimes even a recommended dose can lead to serious and conceivably fatal liver toxicity. Therefore, it is important to clarify understand mechanisms of hepatotoxicity induced by APAP. Gap junctions, formed by connexin, have important roles in maintenance of tissue homeostasis and control of cell growth and differentiation. In the liver, Cx32 is a major gap junction protein whose expression is known to gradually decrease with chronic liver disease progression. In the present study, acute hepatotoxic effects of APAP were found to be reduced in Cx32 dominant negative transgenic rats lacking normal gap junctional intercellular communication in the liver. In littermate wild-type rats, the injured centrilobular hepatocytes were positive for TUNEL staining and featured elevated expre ssion of cleaved caspase-3 and Cx43, which is not expressed in normal hepatocytes. These results suggest that APAP hepatotoxicity involves apoptosis, and induction of Cx43 expression may play an important role in the apoptotic signaling. Moreover, gap junctional functions of Cx32 can play important roles in removing damaged hepatocytes by apoptosis for liver tissue homeostasis.
- Subjects :
- Animals
Apoptosis drug effects
Chemical and Drug Induced Liver Injury pathology
Connexin 43 drug effects
Connexins metabolism
Female
Male
Rats
Rats, Sprague-Dawley
Gap Junction beta-1 Protein
Acetaminophen toxicity
Analgesics, Non-Narcotic toxicity
Chemical and Drug Induced Liver Injury metabolism
Connexin 43 metabolism
Gap Junctions drug effects
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1533-1601
- Volume :
- 38
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Toxicologic pathology
- Publication Type :
- Academic Journal
- Accession number :
- 20097795
- Full Text :
- https://doi.org/10.1177/0192623309357951