Caffeic acid enhancement of cocaine-induced hepatotoxicity.
Price-DJ; Muro-Cacho-CA; Kulkarni-AP; Harbison-RD
Toxicologist 2001 Mar; 60(1):79-80
Cocaine has been reported to produce hepatic necrosis and apoptosis. Caffeic acid is a ubiquitous ingredient in beverages, tobacco, fruits and vegetables. The objective of this study was to determine if concomitant treatment with cocaine and caffeic acid would enhance cocaine-induced hepatotoxicity. Male ICR mice were administered caffeic acid (125 mg/kg, i.p.) and 20-min later cocaine (60 mg/kg, i.p.), with sacrifice 24 hr after administration of cocaine. A 4-fold increase in serum alanine aminotransferase activity (ALT) occurred in animals treated with caffeic acid and cocaine (12.000 SF Units/mL) compared to animals treated with cocaine alone (3,000 SF Units/mL). Caffeic acid pretreatment did not significantly reduce hepatic glutathione or esterase activity. The pretreatment did, however, increase cocaine-induced hepatic necrosis and cause a 2 fold increase in apoptosis at 4 hr. a 6 fold increase at 24 hr, and a 12 fold increase at 7 days. Apoptosis was measured using the TUNEL method. Histopathological evaluation indicated that with caffeic acid pretreatment, necrosis was in the same compartments as apoptosis, and occurred at the same time periods. The profound hepatic necrosis was observed in the midzonal and centrilobular areas. The results of this study indicate that caffeic acid can significantly increase cocaine-induced hapatotoxicity, and this enhancement does not appear to be a glutathione or esterase dependent mechanism.
Hepatotoxicity; Hepatotoxins; Acids; Drugs; Drug-abuse; Laboratory-animals; Animals; Animal-studies; Histopathology
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California
Sunshine Education Research Center, College of Public Health, University of South Florida, Tampa, FL 33612-3805