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Caffeic acid enhancement of cocaine-induced hepatotoxicity.

Authors
Price-DJ; Muro-Cacho-CA; Kulkarni-AP; Harbison-RD
Source
Toxicologist 2001 Mar; 60(1):79-80
NIOSHTIC No.
20025753
Abstract
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.
Keywords
Hepatotoxicity; Hepatotoxins; Acids; Drugs; Drug-abuse; Laboratory-animals; Animals; Animal-studies; Histopathology
CAS No.
70-18-8
Publication Date
20010301
Document Type
Abstract
Funding Amount
1212720
Funding Type
Grant
Fiscal Year
2001
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-T42-CCT-412874
Issue of Publication
1
ISSN
1096-6080
Source Name
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California
State
FL
Performing Organization
Sunshine Education Research Center, College of Public Health, University of South Florida, Tampa, FL 33612-3805
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