Short-term acetaldehyde exposure depresses ventricular myocyte contraction: role of cytochrome P450 oxidase, xanthine oxidase, and lipid peroxidation.

BACKGROUND: Chronic alcoholism leads to the development of alcoholic cardiomyopathy, manifested as ventricular dilation and impaired ventricular contractility. However, the specific toxic mechanism responsible for alcoholic cardiomyopathy remains unclear. One major candidate toxin is the first metabolic product of ethanol, acetaldehyde (ACA). This study was designed to examine the role of cytochrome P450 oxidase 2E1 (CYP 2E1), xanthine oxidase, and lipid peroxidation in the short-term ACA exposure-induced mechanical defects in adult rat ventricular myocytes.

METHODS: Mechanical and intracellular Ca2+ properties were evaluated by an IonOptix SoftEdge system. Lipid peroxidation was assessed with malondialdehyde levels by using high-performance liquid chromatography.

RESULTS: Short-term (4- to 6-hr) culture of myocytes with ACA (1-100 microM) in sealed containers with silicone septum depressed cell-shortening amplitude, maximal velocity of shortening/relengthening, and prolonged duration of relengthening, as well as intracellular Ca2+ clearing without any effect on the duration of shortening and electrically stimulated an intracellular Ca2+ increase. It is interesting to note that the ACA-induced effects on myocyte mechanical properties were abolished with co-treatment of the lipid peroxidation inhibitor butylated hydroxytoluene (20 microM), the CYP 2E1 inhibitor diallyl sulfide (100 microM), and the xanthine oxidase inhibitor allopurinol (100 microM). Short-term incubation of ACA with the myocytes also produced a significant increase of the lipid peroxidation end product malondialdehyde, which may be prevented by butylated hydroxytoluene.

CONCLUSIONS: Collectively, these data provided evidence that ACA depressed cardiomyocyte mechanical function at micromolar levels, possibly through mechanisms related to CYP oxidase, xanthine oxidase, and lipid peroxidation.