Oxidative Stress and Genotoxicity Induced by Ketorolac on the Common Carp Cyprinus carpio M. Galar-Mart  ınez, 1 S. Garc  ıa-Medina, 2 L. M. G omez-Olivan, 3 I. P erez-Coyotl, 1 D. J. Mendoza-Monroy, 1 R. E. Arrazola-Morgain 1 Departamento de Farmacia, Laboratorio de Toxicolog  ıa Acu atica, Escuela Nacional de Ciencias Biol  ogicas, Instituto Polit ecnico Nacional, Ciudad de M exico, M exico 2 Unidad Anal  ıtica de la Unidad de Farmacolog  ıa Cl  ınica, Facultad de Medicina - UNAM, Nezahualc oyotl, Edo de M exico 3 Departamento de Farmacia, Facultad de Qu  ımica, Laboratorio de Toxicolog  ıa Ambiental, Universidad Aut  onoma del Estado de M exico, Toluca, M exico Received 11 August 2014; revised 23 December 2014; accepted 29 December 2014 ABSTRACT: The nonsteroidal anti-inflammatory drug ketorolac is extensively used in the treatment of acute postoperative pain. This pharmaceutical has been found at concentrations of 0.2–60 mg/L in diverse water bodies around the world; however, its effects on aquatic organisms remain unknown. The present study, evaluated the oxidative stress and genotoxicity induced by sublethal concentrations of ketorolac (1 and 60 mg/L) on liver, brain, and blood of the common carp Cyprinus carpio. This toxicant induced oxida- tive damage (increased lipid peroxidation, hydroperoxide content, and protein carbonyl content) as well as changes in antioxidant status (superoxide dismutase, catalase, and glutathione peroxidase activity) in liver and brain of carp. In blood, ketorolac increased the frequency of micronuclei and is therefore genotoxic for the test species. The effects observed were time and concentration dependent. V C 2015 Wiley Periodicals, Inc. Environ Toxicol 00: 000–000, 2015. Keywords: ketorolac; oxidative stress; lipid peroxidation; hydroperoxides; oxidized proteins; antioxidant enzymes; genotoxicity; micronucleus; DNA; Cyprinus carpio INTRODUCTION Pharmaceutical products are biologically active and persis- tent substances that have been recognized as a constant threat to the stability of the environment. These toxicants form part of the group termed “emerging contaminants” and many tons of them are produced and consumed annually around the world. This explains their occurrence in the envi- ronment, particularly in aquatic ecosystems which they enter through municipal and hospital wastewater discharges (Christen et al., 2010; Ginebreda et al., 2010). These com- pounds have been designed to elicit a specific biological action in the body and often resist inactivation prior to inducement of their intended therapeutic effect, these proper- ties being paradoxically responsible for both their bioaccu- mulation and toxic effect on hydrobionts (Santos et al., 2010). One of the most frequently used pharmaceutical groups is that of the nonsteroidal anti-inflammatory drugs (NSAIDs), which includes ketorolac (KTC). Many of these remedies are sold without prescription, favoring self- medication, and overuse, and increasing the concentrations at which they are found in the environment (Parolini et al., 2010; Islas-Flores et al., 2013). In the case of KTC, it has Correspondence to: M. Galar-Mart  ınez; e-mail: mgalarm@ipn.mx; marcela_galar_martinez@hotmail.com or S. Garc  ıa-Medina, e-mail: mgalarm@ipn.mx; marcela_galar_martinez@hotmail.com Contract grant sponsor: Secretar  ıa de Investigaci on y Posgrado of the Instituto Polit ecnico Nacional SIP-IPN. Contract grant numbers: 20131086; 20141042 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/tox.22113 V C 2015 Wiley Periodicals, Inc. 1