Aminosalicylates toxicity in pregnant carriers of ulcerative colitis, perinatal outcome

Abstracts / Toxicology Letters 259S (2016) S73–S247

four weeks. The sperm samples were collected from the epididymis in 2 mL of saline (0.9% NaCl) analyzing the sperm concentration, motility, morphology and viability, as well as the sperm chromatin dispersion (SCD). Statistical analysis was performed with the SPSS 20 statistical package, an ANOVA, and Tukey tests were applied to compare the means between treatments. Results: The overall ANOVA analysis showed significant differences between groups in sperm concentration (P = 0.009) and motility (P = 3.0E10−5). Post hoc Tukey test showed a significant difference in sperm concentration between groups 1 and 2, compared to the control group (P = 0.033 and 0.009, respectively), and a linear regression analysis showed a correlation between the fragmentation index with the sperm concentration and sperm progressive motility (r = −0.794, P = 0.011; −0.949, P = 9.6E−5, respectively). For the variable fragmentation index, values for the control and As-treated groups were: 3.000 ± 1.000, 66.333 ± 4.163, and 82.333 ± 4.932, respectively; the ANOVA analysis showed significant differences between groups (P = 5.1496E−7); besides the post hoc Tukey test resulted in significant differences for groups 1 and 2 with respect to the control group (P = 7.1878E−7, and 2.0E−6, respectively). Conclusions: Preliminary results showed a decrease in sperm concentration and motility by As exposure, which could be related to the genotoxic damage caused by this metalloid. The sperm DNA fragmentation may be related to other factors such as the formation of reactive oxygen species (ROS), methylation of genes involved in cell cycle regulation or chromosome damage. Financial support: Universidad Autónoma de Coahuila, Torreón, Coahuila, Mexico. http://dx.doi.org/10.1016/j.toxlet.2016.07.568 PP25.13 Effects of subchronic exposure to sibutramine and/or rosuvastatin on reproductive parameters of Wistar rats P.V. Silva 1 , C.S. Borges 1 , T.L. Pacheco 1 , T.M. Figueiredo 1 , J.L. Rosa 1 , G. Missassi 2 , G.A.A. Leite 2 , R.F. Silva 2 , M.T. Guerra 1 , A.F.G.M. Dias 1 , W.D.G. Kempinas 1 1 2

Institute of Biosciences – UNESP, Botucatu, São Paulo, Brazil Institute of Biology – UNICAMP, Campinas, São Paulo, Brazil

Introduction: Obesity is a public health problem that has been rising worldwide. Considered a disease, it is characterized by dyslipidemia and related to various morbidities such as metabolic syndrome and cancer. Sibutramine, an anorectic drug, has been used alone or associated with hypolipidemic drugs, such as rosuvastatin, to treat obese patients. However, effects on the reproductive parameters of these patients were not investigated. Objective: To investigate the effects of subchronic exposure to sibutramine and/or rosuvastatin on reproductive parameters in male rats. Materials and methods: Adult Wistar male rats (90 days) were separated into control (C; saline and dimethyl sulfoxide), sibutramine (S; 10 mg/kg), rosuvastatin (R; 5 mg/kg) and sibutramine combined to rosuvastatin (S + R) groups (n = 7–13/group) and treated orally for 30 days in the dark cycle period. After treatment, the following parameters were analyzed: body and reproductive organ weights, sexual behavior, fertility after natural mating and in utero artificial insemination and sperm parameters. Results: There was a significant reduction in the body weight of S and S + R groups when compared to C group. In these animals, there was a decrease in the absolute weights of full seminal vesicle and ventral prostate, acceleration of epididymal sperm transit

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time and reduction of sperm numbers in the epididymal cauda. Sexual behavior, fertility after natural mating, sperm production and motility were not altered by the treatment. On the other hand, fertility potential was reduced after in utero artificial insemination in the S group. Conclusions: The anorectic action of sibutramine was confirmed by the reduction in body weight of the S and S + R groups. In addition, these animals showed reduced reproductive organ weights and epididymal sperm reserves and aceleration of epididymal sperm transit time, leading to reduced fertility observed after in utero artificial insemination. By contrast, rosuvastatin had no effect and did not potentiate sibutramine effects on the reproductive parameters investigated. Financial support: FAPESP (grant #2014/15566-2). http://dx.doi.org/10.1016/j.toxlet.2016.07.569 PP25.14 Aminosalicylates toxicity in pregnant carriers of ulcerative colitis, perinatal outcome H.O. Favela 1 , M.N. Betancourt 1 , M.J. Morán 1 , R.Y. Jaramillo 2 , C.J. Nares 2 , G.F. Solís 2 , O.J. Zambrano 1 , P.A. Carrillo 1 , R.I. Balderas 3 , H.J. Favela 4 1 Biology Cell and Ultraestructure Department, Biomedical Research Center, Faculty of Medicine, Autonomous Univeristy of Coahuila, COAH, Mexico 2 Instituto Mexicano del Seguro Social UMAE No. 71, COAH, Mexico 3 Department of Genomics and Genetic Engineering, Faculty of Chemical Sciences of the Autonomous University of Nuevo Leon, Mexico 4 Faculty of Chemistry of the Juarez University of the State of Durango, DGO, Mexico

Introduction: Ulcerative colitis affects persons in reproductive age. Its attention in the pregnancy represents a multidisciplinary challenge. Objective: To describe the toxicity and perinatal outcomes in patients with ulcerative colitis and pregnancy treated with aminosalicylates and steroids. Materials and methods: Study design: case series, observational, descriptive, retrospective, not intervencional. Seven patients were analyzed with ulcerative colitis, pregnant, from January 1, 2010 until May 30, 2015. There was evaluated diagnosis, evolution of the illness, medical, obstetric complications, and perinatal outcomes. Inclusion: Patients with CUCI with histological assertion, pregnant women. Exclusion: absence of histopathological report. The statistical analysis carried out by scattering measurements, analysis of central tendency, Pearson correlation and Statistical analysis program SPSS Version 23. Results: Age average was 29 years. The correlation between the age gestational and the weight of the product was .909 (p = 0.01) with a significance of 99%. The age gestational was 38.6 weeks (SD ± 1.31) and the weight of the newborns was 2671 g (SD ± 579.78). The patients who did not suspend its treatment with aminosalicylates/steroids or they initiated them in pregnancy, had an association of .538 in accordance with the grade of severity of the illness (just as not pregnant women). There were no significant differences in the extension of the illness (Montreal) (p = 0.94), and the gestational age (p = 0.49) as for the activity/reference during the pregnancy. Neither abortions nor congenital malformations were brought in any case. Conclusions: The aminosalicylates are safe during the pregnancy. They allow to term pregnancy, with better survival for the

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Abstracts / Toxicology Letters 259S (2016) S73–S247

product in spite of presenting underweight at birth, collaborating with a low morbidity and maternal mortality. http://dx.doi.org/10.1016/j.toxlet.2016.07.570 PP25.15 Taurine prevents sexual dysfunction of alloxan-induced diabetic mice E. Martínez-Galero 1 , T.T.R. Torres-Carrillo 1 , G.A. Arroyo-Razo 2 , L. 1 ˜ Garduno-Siciliano 1 Departamento de Farmacia, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México 2 Lab. de Química Verde, FES-Cuautitlán-UNAM, Estado de México, México

Introduction: A common chronic complication among diabetic men is sexual dysfunction. It is therefore important to evaluate compounds with little or no toxicity which may decrease potentially diabetes-induced sexual dysfunction and thus improve men life quality. Protein glycation and oxidative damage are two mechanisms involved in the development of sexual dysfunction. Taurine (Tau) is a non toxic amino acid with antioxidant activity and antiglycation. Objective: The aim of this study was to investigate the effect of taurine on sexual dysfunction caused by diabetes in mice. Materials and methods: ICR male mice sexually mature were randomized into five groups: (1) Negative Control, (2) Tau 2%, (3) Diabetic Control, (4) Diabetic-Tau 1% and (5) Diabetic-Tau 2%. Diabetes was induced administrating alloxan 200 mg/kg i.p. and Tau treatment was provided by dissolving the amino acid in drinking water. Water consumption, blood glucose and body weight were determined weekly along study (42 days). On day 40, animals were subjected to a sexual behavior test and were sacrificed at the end of treatments. Reproductive organs were collected and weighed. Spermatozoa were collected from epididymis and vas deferens to evaluate spermatic account viability and motility. Results: In addition to hyperglycemia and polydipsia, which are typical signs of diabetes, alloxan-treated mice exhibited sexual behavior deterioration evidenced by decreased number of mounting trials, as well as by increased licking behavior and mounting latencies. Further, alloxan-treated mice decreased sperm count and motility. Meanwhile, taurine-treated mice did not modified blood glucose levels, but significantly reversed deterioration of sexual behavior and sperm quality induced by alloxan-treatment. Conclusions: According to the results presented above, it can be concluded that taurine may be a potential treatment to prevent sexual dysfunction caused by diabetes. Financial support: This work was funded by the SIP20144409 project. http://dx.doi.org/10.1016/j.toxlet.2016.07.722 P26: Target Organ Toxicity PO26.1 Mechanistic studies on diethylene glycol poisoning to develop new therapies? K.E. McMartin, C. Robinson, T. Conrad, G. Landry Dept of Pharmacology, Toxicology, and Neuroscience, LSU Health Sciences Center, Shreveport, LA, USA Objectives: Diethylene glycol (DEG) ingestion, mostly through adulterated pharmaceuticals, has produced numerous mass poi-

sonings in the developing world. DEG poisoning is extremely difficult to diagnose and the only effective treatment has been hemodialysis, which also lacks wide availability. Our goal is to understand the mechanisms of DEG toxicity in order to develop drugs that might be useful, particularly in suspected poisonings world-wide. DEG poisoning is characterized by acute kidney injury, hepatotoxicity and peripheral neuropathy. To understand the mechanism of toxicity, we have shown in human, animal, and cellular studies that diglycolic acid (DGA) appears to be the key metabolite that accumulates and produces a necrotic toxicity in the kidney. The goal of these studies is to confirm that DGA is the toxic metabolite and to assess how it accumulates in target organs. Materials and methods: Adult Wistar rats were gavaged with doses of DGA from 0–300 mg/kg, urine was collected and blood and tissues were collected at 48 h. Studies in human proximal tubule (HPT) cells compared the uptake and efflux of DGA with that of succinate, the dicarboxylate transporter substrate in the kidney. Results: These studies have confirmed that DGA induces a toxic syndrome virtually identical to that of DEG, with renal and hepatic damage. DGA accumulated in kidney and liver tissue only at 300 mg/kg. DGA concentrations in the kidneys and liver correlated with renal and hepatic injury. Histopathologic and chemical analysis showed that DGA exhibited moderate liver damage and marked renal injury, but only at 300 mg/kg. Transport studies showed that DGA was slowly taken up by HPT cells from both the apical and basolateral directions, but was effluxed from cells only in a small amount. Conclusions: These results provide direct evidence for DGA as the toxic metabolite of DEG. The steep dose–response threshold for toxicity suggests a saturable step in DGA transport. DGA appears to accumulate in the kidney due to a slow uptake, but essentially no transport out of the cell. Future studies will assess the transport pathways to design ways to reduce this accumulation and hence DGA toxicity, which could lead to new therapies for DEG poisoning. http://dx.doi.org/10.1016/j.toxlet.2016.07.572 PO26.2 Effects of arginine vasopressin (AVP) deficiency and the use of conivaptan on the blood pressure in normal and spontaneous hypertensive rats (SHR) M. Villanueva-Rodríguez 1 , A. Organista-Esparza 1 , V. 1 , P. Huerta-Carreón 1 , C.V. Rivera-Cerecero 2 , R. ˜ Vinuela-Berni Chavira-Ramirez 3 , A. Quintanar-Stephano 1 1 Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Laboratorio de Neuroinmunoendocrinología, Universidad Autónoma de Aguascalientes, Aguascalientes, Mexico 2 Bioterio Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, Mexico 3 Laboratorio de Hormonas Esteroides, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Ciudad de México, Mexico

Introduction: Previously, we described that neurointermediate pituitary lobectomy (NIL) in normotensive rats, induced an early but transient diabetes insipidus and permanent low mean blood pressure (MBP). Objective: Study the mechanisms that regulate blood pressure and fluid balance in AVP deficient animals. Materials and methods: We evaluated the effects of NIL on AVP and oxytocin (OT) serum levels and MBP, water intake and urine output, urine Na and K concentrations and Na and K serum levels from time 0 to 6 h and at 3, 15, 45 and 90 days post NIL, whereas the renin-angiotensin II-aldosterone system (RAAS) was assessed