Toxic effects of carvacrol, caryophyllene oxide, and ascaridole from essential oil of Chenopodium ambrosioides on mitochondria

Journal Article · Sun Nov 01 00:00:00 EDT 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.08.001· OSTI ID:21344773

Monzote, Lianet ^[1]; Stamberg, Werner; Staniek, Katrin ^[2]; Gille, Lars ^[2]

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1. Parasitology Department, Institute of Tropical Medicine 'Pedro Kouri', Apartado Postal No. 601, Marianao 13, Havana City (Cuba)
2. Molecular Pharmacology and Toxicology Unit, Department of Biomedical Sciences, University of Veterinary Medicine Vienna, Veterinaerplatz 1, A-1210 Vienna (Austria)

Chenopodium ambrosioides have been used for centuries in the Americas as a popular remedy for parasitic diseases. The essential oil of this plant possesses anthelmintic activity and is still used in some regions to treat parasitosis and leishmaniasis. However, the Chenopodium oil caused also some fatalities, leading to its commercial disuse. In this work, we studied the mechanism of toxicity of the essential oil and its major pure ingredients (carvacrol, caryophyllene oxide, and ascaridole, which was synthesized from alpha-terpinene) with respect to mammalian cells and mitochondria. We observed that all products, but especially caryophyllene oxide, inhibited the mitochondrial electron transport chain. This effect for carvacrol and caryophyllene oxide was mediated via direct complex I inhibition. Without Fe{sup 2+}, ascaridole was less toxic to mammalian mitochondria than other major ingredients. However, evidence on the formation of carbon-centered radicals in the presence of Fe{sup 2+} was obtained by ESR spin-trapping. Furthermore, it was shown that Fe{sup 2+} potentiated the toxicity of ascaridole on oxidative phosphorylation of rat liver mitochondria. The increase of the alpha-tocopherol quinone/alpha-tocopherol ratio under these conditions indicated the initiation of lipid peroxidation by Fe{sup 2+}-mediated ascaridole cleavage. Further ESR spin-trapping experiments demonstrated that in addition to Fe{sup 2+}, reduced hemin, but not mitochondrial cytochrome c can activate ascaridole, explaining why ascaridole in peritoneal macrophages from BALB/c mice exhibited a higher toxicity than in isolated mitochondria.

• OSTI ID: 21344773
• Journal Information: Toxicology and Applied Pharmacology, Vol. 240, Issue 3; Other Information: DOI: 10.1016/j.taap.2009.08.001; PII: S0041-008X(09)00327-5; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BENZOQUINONES
ELECTRON SPIN RESONANCE
ESSENTIAL OILS
HEME
IRON IONS
LIVER
MITOCHONDRIA
TOXICITY
AROMATICS
BODY
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHARGED PARTICLES
DIGESTIVE SYSTEM
GLANDS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
IONS
MAGNETIC RESONANCE
OILS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OTHER ORGANIC COMPOUNDS
PIGMENTS
PORPHYRINS
QUINONES
RESONANCE