Effects of Dimenhydrinate and Ondansetron Used in Pregnant Rats on Postnatal Morphometric Development

Year 2011, , 1 - 9, 01.01.2011

Kadir Desdicioğlu Neslihan Cankara Emine Hilal Evcil Raziye Desdicioğlu Mehmet Ali Malas

https://doi.org/10.5174/tutfd.2009.02492.1

Abstract

Objective: To determine the effects of dimenhydrinate (DMH) and ondansetron, used as antiemetics during pregnancy, on the length of gestation, maternal weight gain during gestation and postnatal morphometric parameters of pups. Material and Methods: Thirty female Wistar albino rats were used in the study. Three groups comprising 10 rats each were studied: Group 1: control group; Group 2: DMH group; and Group 3: ondansetron group. Rats were impregnated and administered 115 mg/kg/day intramuscular, DMH group, or 10 mg/ kg/day intraperitoneal, ondansetron group. The parameters pertaining to the cranium, thorax and limbs were measured between newborn and adulthood. Results: The increase in mean morphometric parameters during the postnatal period in the DMH group was less than the control group,whereas that in the ondansetron group exceeded the controls (p<0.05). Moreover, when data obtained between weeks 7 and 11 were analyzed for males and females separately, morphometric parameters increased at a slower rate in the DMH than the control group and morphometric parameters increased at a higher rate in the ondansetron than the control group in either sex (p<0.05). Conclusion: DMH and ondansetron used during gestation affect weight gain during gestation, and morphometric development of pups during newborn and lactation periods and adulthood.

Keywords

Antiemetic, developmental anatomy, fetal development, gestation, rat

Effects of Dimenhydrinate and Ondansetron Used in Pregnant Rats on Postnatal Morphometric Development

Abstract

References

• Einarson A, Maltepe C, Navioz Y, Kennedy D, Tan MP, Koren G. The safety of ondansetron for nausea and vomiting of pregnancy: a prospective comparative study. BJOG 2004;111:940-3.
• Gill SK, Einarson A. The safety of drugs for the treatment of nausea and vomiting of pregnancy. Expert Opin Drug Saf. 2007;6:685-94.
• Badell ML, Ramin SM, Smith JA. Treatment options for nausea and vomiting during pregnancy. Pharmacotherapy. 2006;26:1273-87.
• Paauw JD, Bierling S, Cook CR, Davis AT. Hyperemesis gravidarum and fetal outcome. JPEN 2005;29:93-6.
• Gross S, Librach C, Cecutti A. Maternal weight loss associated with hyperemesis gravidarum: a predictor of fetal outcome. Am J Obstet Gynecol. 1989;160:906-9.
• Sullivan CA, Johnson CA, Roach H, Martin RW, Stewart DK, Morrison JC. A pilot study of intravenous ondansetron for hyperemesis gravidarum. Am J Obstet Gynecol. 1996;174:1565-8.
• Mazzotta P, Magee LA. A risk-benefit assessment of pharmacological and nonpharmacological treatments for nausea and vomiting of pregnancy. Drugs. 2000; 59:781-800.
• Magee LA, Mazzotta P, Koren G. Evidence-based view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of pregnancy (NVP). Am J Obstet Gynecol. 2002;186:256-61.
• Tucker ML, Jackson MR, Scales MD, Spurling NW, Tweats DJ, Capel-Edwards K. Ondansetron: pre-clinical safety evaluation. Eur J Cancer Clin Oncol. 1989;25:79-93.
• Mccoll JD, Globus M, Robınson S. Effect of some therapeutıc agents on the developıng rat fetus. Toxicology and applied pharmacology. 1965;7:409-17.
• Czeizel AE, Vargha P. A case-control study of congenital abnormality and dimenhydrinate usage during pregnancy. Arch Gynecol Obstet. 2005;271:113-8.
• Siu SS, Chan MT, Lau TK. Placental transfer of ondansetron during early human pregnancy. Clin Pharmacokinet. 2006;45:419-23.
• LaBorde JB, Hansen DK, Young JF, Sheehan DM, Holson RR. Prenatal dexamethasone exposure in rats: effect of dose, age of exposure, and drug induced hypophagia on malformations and fetal organ weights. Fundam Appl Toxicol. 1992;19:545-54.
• Halpert AG, Olmstead MC, Beninger RJ. Dimenhydrinate produces a conditioned place preference in rats. Pharmacol Biochem Behav. 2003;75:173-9.
• Zhang SW, Bai YZ, Zhang SC, Wang DJ, Zhang T, Zhang D et al. Embryonic development of the striated muscle complex in rats with anorectal malformations. J Pediatr Surg. 2008;43:1452-8.
• Baiy Y, Chen H, Yuan ZW, Wang W. Normal and abnormal embryonic development of the anorectum in rats. J Pediatr Surg. 2004;39:587-90.
• Balbani AP, Montovani JC. Mobile phones: influence on auditory and vestibular systems. Braz J Otorhinolaryngol. 2008;74:125-31.
• Fan W, Huang F, Li C, Qu H, Gao Z, Leng S et al. Involvement of NOS/NO in the development of chronic dental inflammatory pain in rats. Brain Res Rev. 2008;59:324-32.
• Moore KL, Persaud TVN. The Developing Human (Clinically Oriented Embryology) 7 th edn. WB Saunders Company, Philadelphia. 2002;271-302.
• Wells TAG. The Rat. A Practical Guide, Heinemann Educational Books Ltd, London, 1964;1-77
• Malas MA, Dogan S, Evcil EH, Desdicioglu K. Fetal development of the hand, digits and digit ratio (2D:4D). Early Hum Dev. 2006;82:469-75.
• Tyl RW, Chernoff N, Rogers JM. Altered axial skelatal development. Birth Defects Res B Dev Reprod Toxicol. 2007;80:451-72.
• Hobel C, Culhane J. Role of psychosocial and nutritional stress on poor pregnancy outcome. J Nutr. 2003;133:1709-17.
• Mahajan SD, Singh S, Shah P, Gupta N, Kochupillai N. Effect of maternal malnutrition and anemia on the endocrine regulation of fetal growth. Endocr Res. 2004;30:189-203.
• Moran P, Taylor R. Management of hyperemesis gravidarum: the importance of weight loss as a criterion for steroid therapy. Q J Med 2002;95:153-8.
• Hougaard KS, Andersen MB, Kjaer SL, Hansen AM, Werge T, Lund SP. Prenatal stress may increase vulnerability to life events: comparison with the effects of prenatal dexamethasone. Brain Res Dev Brain Res. 2005;159:55-63.
• Williams MT, Hennessy MB, Davis HN. Stress during pregnancy alters rat offspring morphology and ultrasonic vocalizations. Physiol Behav. 1998;63:337-43.
• Finn AL. Toxicity and side effects of ondansetron. Semin Oncol. 1992;19:53-60.
• Tincello DG, Johnstone MJ. Treatment of hyperemesis gravidarum with the 5-HT3 antagonist ondansetron (Zofran). Postgrad Med J. 1996;72:688-9.
• Halpert AG, Olmstead MC, Beninger RJ. Mechanisms and abuse liability of the anti-histamine dimenhydrinate. Neurosci Biobehav Rev. 2002;26:61-7.
• Yost NP, McIntire DD, Wians FH Jr, Ramin SM, Balko JA, Leveno KJ. A randomized, placebo-controlled trial of corticosteroids for hyperemesis due to pregnancy. Obstet Gynecol. 2003;102:1250-4.
• Burdan F. Developmental toxicity evaluation of ibuprofen and tolmetin administered in triple daily doses to Wistar CRL:(WI)WUBR rats. Birth Defects Res B Dev Reprod Toxicol. 2004;71:321-30.
• Burdan F, Szumilo J, Marzec B, Klepacz R, Dudka J. Skeletal developmental effects of selective and nonselective cyclooxygenase-2 inhibitors administered through organogenesis and fetogenesis in Wistar CRL:(WI)WUBR rats. Toxicology. 2005;216:204-23.
• Miller MJ, Voelker CA, Olister S, Thompson JH, Zhang XJ, Rivera D et al. Fetal growth retardation in rats may result from apoptosis: role of peroxynitrite. Free Radic Biol Med. 1996;21:619-29.
• Thaete LG, Kushner DM, Dewey ER, Neerhof MG. Endothelin and the regulation of uteroplacental perfusion in nitric oxide synthase inhibition-induced fetal growth restriction. Placenta. 2005;26:242-50.
• Ishida M, Hiramatsu Y, Masuyama H, Mizutani Y, Kudo T. Inhibition of placental ornithine decarboxylase by DL-alpha-difluoromethyl ornithine causes fetal growth restriction in rat. Life Sci. 2002;70:1395-405.
• Sugden MC, Langdown ML, Munns MJ, Holness MJ. Maternal glucocorticoid treatment modulates placental leptin and leptin receptor expression and materno-fetal leptin physiology during late pregnancy, and elicits hypertension associated with hyperleptinaemia in the early-growth-retarded adult offspring. Eur J Endocrinol. 2001;145:529-39.
• Siu SS, Yip SK, Cheung CW, Lau TK. Treatment of intractable hyperemesis gravidarum by ondansetron.Eur J Obstet Gynecol Reprod Biol.2002;105:73-4.
• Koren G, Maltepe C. Pre-emptive therapy for severe nausea and vomiting of pregnancy and hyperemesis gravidarum. J Obstet Gynaecol. 2004;24:530-3.
• Troyer WA, Pereira GR, Lannon RA, Belik J, Yoder MC. Association of maternal lithium exposure and premature delivery. J Perinatol. 1993;13:123-7.
• Kozma C. Neonatal toxicity and transient neurodevelopmental deficits following prenatal exposure to lithium: Another clinical report and a review of the literature. Am J Med Genet A. 2005;132:441-4.