Diverse antioxidants protect against acetaminophen hepatotoxicity

✍ Scribed by Helieh S. Oz; Craig J. McClain; Herbert T. Nagasawa; Mukunda B. Ray; Willem JS. de Villiers; Theresa S. Chen

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 193 KB
• Volume: 18
• Category: Article
• ISSN: 1095-6670
• DOI: 10.1002/jbt.20042

✦ Synopsis

The reactive oxygen species-sensitive transcription nuclear factor-B (NF-B) plays a pivotal role in the development of acetaminophen (APAP) hepatotoxicity. We investigated the efficacy of a diverse series of antioxidants in preventing APAP-induced hepatotoxicity. BALB/c mice were divided into four groups and provided with antioxidants incorporated into chow as follows: (1) control diet; or diet supplemented with (2) S-adenosylmethionine (SAMe); (3) green tea polyphenols (GrTP); or (4) (RS)-n-propylthiazolidine-4(R)-carboxylic acid (PTCA). After 5 days on these diets, the animals were further subdivided into (A) given an IP injection with APAP (750 mg/kg), or (B) kept as untreated controls. The animals were sacrificed at 0, 4 h, and 24 h following APAP administration. PAP/vehicle induced marked decreases in hepatic reduced glutathione (GSH) levels and endogenous SAMe concentrations (46%) when compared to controls. APAP also caused severe centrilobular necrosis and marked increase in serum enzyme ALT activity (38-fold). Oral administration of antioxidants significantly attenuated the APAP-induced liver damage and depletion of hepatic GSH. There were profound increases in serum TNF-␣ levels at 4 h following APAP administration in nonsupplemented compared to antioxidant-treated animals, but no significant differences noted after 24 h. Serum amyloid A increased in APAP-challenged mice irrespective of antioxidant treatment. Finally, hepatic SAMe concentrations were drastically decreased 24 h This paper was partially presented at FASEB 2004, Washington