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Acute cocaine exposure up-regulates complement expression in rabbit heart.
E J Tanhehco1, K Yasojima, P L McGeer
1University of Michigan Medical School, Department of Pharmacology, Ann Arbor, MI, USA.
The Journal of Pharmacology and Experimental Therapeutics
|December 22, 1999
Summary
Cocaine may harm the heart by increasing complement system proteins in the heart muscle. Heparin may reduce this cocaine-induced heart damage by blocking the formation of the membrane attack complex (MAC).
Area of Science:
- Cardiovascular Pharmacology
- Immunology
- Toxicology
Background:
- The cardiotoxic mechanisms of cocaine are not fully understood.
- The heart can produce complement components, which may cause injury.
- This study investigates cocaine's effect on myocardial complement expression.
Purpose of the Study:
- To determine if cocaine up-regulates complement expression in the myocardium.
- To explore the role of reactive oxygen species and heparin in cocaine-induced cardiotoxicity.
Main Methods:
- Isolated rabbit hearts were perfused with cocaine, procaine, or its isomer.
- Myocardial mRNA expression of complement components (C1q, C1r, C8, C9, C3) was measured.
- In vivo cocaine administration and effects of an antioxidant and heparin were assessed.
- Membrane attack complex (MAC) formation was evaluated.
Main Results:
- Cocaine and procaine significantly increased myocardial mRNA expression for C1q, C1r, C8, C9, and C3.
- (+)-cocaine had no significant effect on complement mRNA expression.
- In vivo cocaine administration also increased myocardial complement mRNA.
- Both cocaine and procaine enhanced MAC formation; antioxidant attenuated increases, while heparin reduced MAC formation but not mRNA transcription.
Conclusions:
- Cocaine may induce myocardial injury by up-regulating local complement expression, potentially through reactive oxygen species.
- Heparin may mitigate cocaine's cardiotoxic effects by inhibiting MAC formation.