Acute effects of cocaine, morphine and their combination on bioenergetic function and susceptibility to oxidative stress of rat liver mitochondria

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Cocaine and heroin are frequently co-abused in a combination known as speedball. Despite the relevance of the liver in the metabolism and detoxification of these drugs, little is known about the impact of speedball on liver function.

Main methods

In this work, we evaluated the effects of cocaine, morphine and morphine + cocaine (Mor + Coc) combination (1:1) in isolated rat liver mitochondria, upon glutamate/malate or succinate energization, on bioenergetics and oxidative stress-related parameters by using Clark O2, Ca2 +, TPP+ and pH electrodes and by measuring thiobarbituric acid reactive substances (TBARS) and H2O2 production.

Key findings

Cocaine and Mor + Coc at the higher concentrations (1 mM) similarly increased O2 consumption at state 2, state 4 and state oligomycin. In these conditions, maximum respiration was decreased only upon glutamate/malate energization, suggesting an involvement of complex I. Morphine (1 mM) only increased state 2 respiration. Cocaine and Mor + Coc induced a similar decrease in maximum mitochondrial membrane potential and in ADP-induced depolarization, whereas morphine had no effect. The drugs and their combination similarly decreased mitochondrial ATPase activity and had no effect on Ca2 +-induced permeability transition. Morphine and Mor + Coc prevented lipid peroxidation, since in these conditions there was a decrease in O2 consumption and in TBARS upon ADP/Fe2 + stimulus, and a decrease in H2O2 formation, suggesting an antioxidant effect. Interestingly, heroin did not share morphine antioxidant properties.


Our results show that the sequential direct exposure of liver mitochondria to morphine and cocaine does not alter the effects observed in the presence of each drug alone.

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