Cyto-genotoxicity and oxidative stress in common carp (Cyprinus carpio) exposed to a mixture of ibuprofen and diclofenac

Thirty million people worldwide consume each day nonsteroidal anti-inflammatory drugs (NSAIDs), a heterogeneous group of pharmaceuticals used for its analgesic, antipyretic, and anti- inflammatory properties. Recent studies report high NSAID concentrations in wastewater treat- ment plant effluents, in surface, ground, and drinking water, and in sediments. NSAIDs are also known to induce toxicity on aquatic organisms. However, toxicity in natural ecosystems is not usu- ally the result of exposure to a single substance but to a mixture of toxic agents, yet only a few studies have evaluated the toxicity of mixtures. The aim of this study was to evaluate the toxicity induced by diclofenac (DCF), ibuprofen (IBP), and their mixture on a species of commercial inter- est, the common carp Cyprinus carpio. The median lethal concentration of IBP and DCF was determined, and oxidative stress was evaluated using the following biomarkers: lipid peroxidation and activity of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxi- dase. Cyto-genotoxicity was evaluated by micronucleus test, comet assay, and the specific activity of caspase-3. Results show that DCF, IBP, and a mixture of these pharmaceuticals induced free radical production, oxidative stress and cyto-genotoxicity in tissues of C. carpio. However, a greater effect was elicited by the mixture than by either pharmaceutical alone in some biomarkers evaluated, particularly in gill.Secretaria de Investigacion y Estudios Avanzados de la UAEM (Project 3722/ 2014CID)

Environmentally relevant concentrations of glibenclamide induce oxidative stress in common carp (Cyprinus carpio).

Artículo cientifico en modalidad embargadoThe hypoglycemic pharmaceutical glibenclamide (GLB) is widely used around the world. This medication is released into the environment by municipal, hospital and industrial wastewater discharges. Although there are reports of its environmental occurrence in the scientific literature, toxicity studies on aquatic species of commercial interest such as the common carp Cyprinus carpio are scarce. The present study aimed to evaluate the oxidative stress induced on C. carpio by environmentally relevant concentrations of GLB. Biomarkers of oxidative damage such as hydroperoxide content, lipid peroxidation and protein carbonyl content were evaluated as well as the activity of the antioxidant enzymes superoxide dismutase and catalase. The concentration of GLB was determined in water as well as in gill, liver, muscle, brain and blood of carp at 12, 24, 48, 72 and 96 h. The findings obtained in the study prove that GLB induces in- creases in biomarkers of oxidative damage and antioxidant enzyme activity in the teleost C. carpio, that his response is not concentration dependent and that the organs evaluated bioconcentrate this hypo- glycemic agent. These findings permit us to conclude that the presence of GLB in water bodies represents a risk for aquatic species

Toxicological hazard induced by sucralose to environmentally relevant concentrations in common carp (Cyprinus carpio)

Sucralose (SUC) is an artificial sweetener that is now widely used in North American and Europe; it has been de- tected in a wide variety of aquatic environments. It is considered safe for human consumption but its effects in the ecosystem have not yet been studied in depth, since limited ecotoxicological data are available in the peer- reviewed literature. This study aimed to evaluate potential SUC-induced toxicological hazard in the blood, brain, gill, liver and muscle of Cyprinus carpio using oxidative stress biomarkers. Carps were exposed to two dif- ferent environmentally relevant concentrations (0.05 and 155 μg L− 1) for different exposure times (12, 24, 48, 72 and 96 h). The following biomarkers were evaluated: lipid peroxidation (LPX), hydroperoxide content (HPC) and protein carbonyl content (PCC), as well as the activity of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT). SUC was determined by high pressure liquid chromatography tandem mass spectrometry tech- niques (HPLC)–MS/MS. Results show a statically significant increase in LPX, HPC, PCC (P b 0.05) especially in gill, brain and muscle, as well as significant changes in the activity of antioxidant enzymes in gill and muscle. Fur- thermore, the biomarkers employed in this study are useful in the assessment of the environmental impact of this agent on aquatic species

Comparative study of diclofenac-induced embryotoxicity and teratogenesis in Xenopus laevis and Lithobates catesbeianus, using the frog embryo teratogenesis assay: Xenopus (FETAX)

Artículo científico que evalúa los efectos teratogénicos y embritóxicos de diclofenacos en dos especies de anfibiosWater is an increasingly deteriorated, limited natural resource due to population increase and industrialization. Also, the widespread use of pharmaceuticals in modern society leads to their presence in domestic, hospital and industrial effluents. Due to their analgesic properties, some of the most commonly used pharmaceuticals are non- steroidal anti-inflammatory drugs (NSAIDs). High concentrations of one these products, diclofenac (DCF), have been detected in effluents and water bodies of different countries, including Mexico. Diverse studies show that trace amounts (ng L−1 to μg L−1) of this compound induce toxicity on aquatic organisms such as algae, microcrustaceans and fish. However, studies on its potential toxicity during development in species of commer- cial interest such as the American bullfrog Lithobates catesbeianus are scarce. The present study aimed to evaluate DCF-induced teratogenesis and embryotoxicity in Xenopus laevis and L. catesbeianus, a species marketed as a nutritional meat source in Mexico, using the frog embryo teratogenesis assay: Xenopus (FETAX). Oocytes in mid-blastula transition were exposed for 96 h to 1, 4, 8, 16, 32 and 62.5 mg DCF L−1. The criteria evaluated were mortality, malformation and growth inhibition. The teratogenic index was 4.2 in L. catesbeianus, three fold higher than the reference limit (1.5), and 3.9 in X. laevis. Diclofenac induced diverse malformations in both species, the most frequent of these being axial malformations in the tail and notochord, edema and stunted growth. Results indicate that DCF is a potentially teratogenic compound and is toxic during development in X. laevis and L. catesbeianus, a species which, due to its sensitivity, can be used to evaluate the toxicity of pharma- ceutical products, using FETAX.CONACyT-Mexico, project 25110

Estrés oxidativo producido por antiinflamatorios no esteroideos sobre el bioindicador Hyalella azteca

capitulo de libroCon base en los resultados obtenidos en el presente estudio de toxicidad aguda y a la clasificación europea, que considera peligroso ambiental- mente a aquellos fármacos cuya concentración letal media sea menor a 100 mg/L, los AINE; diclofenaco, paracetamol, ibuprofeno, naproxeno y ácido acetilsalicílico, pueden ser considerados dañinos para los ecosiste- mas acuáticos. Los AINE (diclofenaco, paracetamol, ibuprofeno, naproxeno y ácido aceti- lsalicílico) son capaces de producir estrés oxidativo sobre Hyalella azteca, reflejándose en los incrementos de lipoperoxidación y del contenido de proteínas carboniladas, y en los cambios producidos en la actividad de las enzimas antioxidantes SOD, CAT y GPx.conacy

Geno-and cytotoxicity induced on Cyprinus carpio by aluminum, iron, mercury and mixture thereof.

Metals such as Al, Fe and Hg are used in diverse anthropogenic activities. Their presence in water bodies is due mainly to domestic, agricultural and industrial wastewater discharges and constitutes a hazard for the organisms inhabiting these environments. The present study aimed to evaluate geno- and cyto- toxicity induced by Al, Fe, Hg and the mixture of these metals on blood of the common carp Cyprinus carpio. Specimens were exposed to the permissible limits in water for human use and consumption according to the pertinent official Mexican norm [official Mexican norm NOM-127-SSA1-1994] Al (0.2 mg L 1), Fe (0.3 mg L 1), Hg (0.001 mg L 1) and their mixture for 12, 24, 48, 72 and 96 h. Bio- markers of genotoxicity (comet assay and micronucleus test) and cytotoxicity (caspase-3 activity and TUNEL assay) were evaluated. Significant increases relative to the control group (po0.05) were observed in all biomarkers at all exposure times in all test systems; however, damage was greater when the metals were present as a mixture. Furthermore, correlations between metal concentrations and biomarkers of geno- and cytotoxicity were found only at certain exposure times. In conclusion, Al, Fe, Hg and the mixture of these metals induce geno- and cytotoxicity on blood of C. carpio.CONACyT-Mexico, Project 18154

17 β-Estradiol induces cyto-genotoxicity on blood cells of common carp (Cyprinus carpio)

Artículo científico17β-Estradiol, a natural hormone present at high concentrations in aquatic ecosystems, affects and modifies endocrine function in animals. In recent years research workers have expressed concern over its potential effects on aquatic organisms; however, little is known about its capacity to induce genetic damage or the pro-apoptotic effects of such damage on fish. Therefore, this study aimed to evaluate 17β-estradiol-induced cyto-genotoxicity in blood cells of the common carp Cyprinus carpio exposed to different concentrations (1 ng, 1 μg and 1 mg L−1). Peripheral blood samples were collected and evaluated by comet assay, micronucleus test, determination of caspase-3 activity and TUNEL assay at 12, 24, 48, 72 and 96 h of exposure. Increases in frequency of micronuclei, TUNEL-positive cells and caspase-3 activity were observed, particularly at the highest concentration. In contrast, the comet assay detected significant increases at 24 and 96 h with the 1 μg and 1 ng L−1 concentrations respectively. The set of assays used in the present study constitutes a reliable early warning biomarker for evaluating the toxicity induced by this type of emerging contaminants on aquatic species.PRODEP-Me xico, Proyecto 103950

Acesulfame potassium: its ecotoxicity measured through oxidative stress biomarkers in common carp (Cyprinus carpio).

Artículo de toxicidad de contaminantes emergentesAcesulfame potassium (ACS) is a widely-used sweetener worldwide. Its presence has been demonstrated in di- verse bodies of water. However, the deleterious effects this causes in aquatic organisms has not yet been identi- fied, which generates controversy concerning the risks that ACS represents after its disposal into the bodies of water. Thus, the objective of this work was to evaluate if the exposure of ACS in environmentally-relevant con- centrations was capable of producing oxidative stress in blood, liver, gill, brain and muscle of common carp (Cyprinus carpio). With this finality, the carp were exposed to two environmentally-relevant concentrations (0.05 and 149 μg L−1) at different exposure times (12, 24, 48, 72 and 96 h), having controls in the same conditions for each exposure time. Posteriorly, the following biomarkers of damage were evaluated: hydroperoxide content (HPC), level of lipoperoxidation (LPX) and protein carbonyl content (PCC), as well as the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). The results showed that ACS produces significant in- crease in damage biomarkers evaluated in all organs, mainly in gill, brain and muscle, as well as significant changes in the activity of antioxidant enzymes in the same organs. Thus, it is concluded that ACS is capable of pro- ducing oxidative stress in common carp (Cyprinus carpio).Conacyt y SIE

Determination of metals and pharmaceutical compounds released in hospital wastewater from Toluca, Mexico, and evaluation of their toxic impact

Un artículo científicoDue to the activities inherent to medical care units, the hospital effluent released contains diverse contaminants such as tensoactives, disinfectants, metals, pharmaceutical products and chemical re- agents, which are potentially toxic to the environment since they receive no treatment or are not effectively removed by such treatment before entering the drain. They are incorporated into municipal wastewater, eventually entering water bodies where they can have harmful effects on organisms and can result in ecological damage. To determine the toxicological risk induced by this type of eflluents, eight metals and 11 pharmaceuticals were quantified, in effluent from a hospital. Developmental effects, teratogenesis and oxidative stress induction were evaluated in two bioindicator species: Xenopus laevis and Lithobates catesbeianus. FETAX (frog embryo teratogenesis assayeXenopus) was used to obtain the median lethal concentration (LC50), effective concentration inducing 50% malformation (EC50), terato- genic index (TI), minimum concentration to inhibit growth (MCIG), and the types of malformation induced. Twenty oocytes in midblastula transition were exposed to six concentrations of effluent (0.1, 0.3, 0.5, 0.7, 0.9, 1%) and negative and positive (6-aminonicotinamide) controls. After 96 h of exposure, diverse biomarkers of oxidative damage were evaluated: hydroperoxide content, lipid peroxidation, protein carbonyl content, and the antioxidant enzymes superoxide dismutase and catalase. TI was 3.8 in X. laevis and 4.0 in L. catesbeianus, both exceed the value in the FETAX protocol (1.2), indicating that this effluent is teratogenic to both species. Growth inhibition was induced as well as diverse malformation including microcephaly, cardiac and facial edema, eye malformations, and notochord, tail, fin and gut damage. Significant differences relative to the control group were observed in both species with all biomarkers. This hospital effluent contains contaminants which represents a toxic risk, since these substances are teratogenic to the bioindicators used. The mechanism of damage induction may be associated with oxidative stress.Conacy