Propionyl- L -Carnitine As Potential Protective Agent Against Adriamycin-Induced Impairment of Fatty Acid Beta-Oxidation in Isolated Heart Mitochondria

Author： Sayed-Ahmed M.M. Shouman S.A. Rezk B.M. Khalifa M.H. Osman A-M.M. El-Merzabani M.M.

Publisher： Academic Press

ISSN： 1043-6618

Source： Pharmacological Research, Vol.41, Iss.2, 2000-02, pp. : 143-150

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Abstract

Propionyl- l -carnitine (PLC), a natural short-chain derivative of l -carnitine, has been tested in this study as a potential protective agent against adriamycin (ADR)-induced cardiotoxicity in isolated rat heart myocytes and mitochondria. In cardiac myocytes, ADR (0.5 m m) caused a significant (70%) inhibition of palmitate oxidation, whereas, PLC (5 m m) induced a significant (49%) stimulation. Addition of PLC to ADR-incubated myocytes induced 79% reversal of ADR-induced inhibition of palmitate oxidation. In isolated rat heart mitochondria, ADR produced concentration-dependent inhibition of both palmitoyl-CoA and palmitoyl-carnitine oxidation, while PLC caused a more than 2.5-fold increase in both substrates. Preincubation of mitochondria with 5 m m PLC caused complete reversal of ADR-induced inhibition in the oxidation of both substrates. Also ADR induced concentration-dependent inhibition of CPT I which is parallel to the inhibition of its substrate palmitoyl-CoA. In rat heart slices, ADR induced a significant (65%) decrease in adenosine triphosphate (ATP) and this effect is reduced to 17% only by PLC. Results of this study revealed that ADR induced its cardiotoxicity by inhibition of CPT I and &bgr;-oxidation of long-chain fatty acids with the consequent depletion of ATP in cardiac tissues, and that PLC can be used as a protective agent against ADR-induced cardiotoxicity.