Toxicology 147 (2000) 41 – 49 Implications of oxidative stress and inflammatory process in the cytotoxicity of capsaicin in human endothelial cells: lack of DNA strand breakage Franc ¸ois Richeux a,b , Marta Cascante c , Rachid Ennamany a,b , Denise Sanchez a , Ambaliou Sanni d , Dominique Saboureau b , Edmond E. Creppy a, * a Laboratory of Toxicology and Applied Hygiene, Faculty of Pharmaceutical Sciences, Uniersity of Bordeaux 2 Victor Segalen, 146 Rue Leo Saignat, F -33076 Bordeaux, France b Palmer Research, 18 Rue de Coulon, F -33640 Arbanats, France c Facultat de Bioquimica, Departament de Biochimica, Uniersitat de Barcelona, Barcelona, Spain d Deparment of Biochemistry and Cellular Biology, FAST National Uniersity of Be ´nin, 04 BP 0320 Cotonou, Benin Received 8 December 1999; received in revised form 13 January 2000; accepted 28 February 2000 Abstract Capsaicin, a natural product of Capsicum species is known to induce excitation of nociceptive terminals involved in pain perception. Nevertheless, it is utilized by topical application in humans, giving rise to blood capsaicin concentration up to 10–20 M. The effect of capsaicin on human endothelial cells ECV 304 has been investigated. The cytotoxicity and inflammatory properties of capsaicin were evaluated by measuring the capsaicin-stimulated release of soluble intercellular adhesion molecule-1 levels (sICAM-1) into the culture medium; production of reactive oxygen species measured by quantification of lipoperoxidation in endothelial cell membranes; and genotoxicity measured using the comet assay and the DNA fragmentation assay. The concentration inhibiting protein synthesis by 50% after 24-h incubation was found to be 175 M. Capsaicin induced an increase of sICAM-1 release into the culture medium at concentration 100 M. Lipoperoxidation measured by malondialdehyde production increased at capsaicin concentration 200 M. The comet test and DNA fragmentation assay clearly suggested that capsaicin does not induce significant DNA strand breaks within the range of concentrations used. Because the inflammatory reaction and lipid peroxidation may affect cellular functions and lead to cell death, the present data may have important implications for the possible health threats of capsaicin, specially in the case of unreasonable use of capsaicin preparations in pathological situations. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Capsaicin; Human endothelial cells; Cytotoxicity; Oxidative stress; Inflammatory process www.elsevier.com/locate/toxicol 1. Introduction Capsaicin is a neurotoxin present in chilies and red peppers, which are widely used as spices. A * Corresponding author. Tel.: +33-557-571217; fax: +33- 556-986685. E-mail address: edmond.creppy@tox.u-bordeaux2.fr (E.E. Creppy) 0300-483X/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII:S0300-483X(00)00184-0