Chemical and Biological Effects of Digoxin on Albino Rat Fetuses

Authors

  • Abd El Wahab El Ghareeb Zoology Department, Faculty of science, Cairo University, Cairo
  • Said Abd El Rahman Mostafa Chemistry Department, Faculty of science, Cairo University, Cairo
  • Heba Ali Zoology Department, Faculty of science, Cairo University, Cairo
  • Talal Jubayr Al-harthi Zoology department, Faculty of Science, Taif University, Saudi Arabia.

Keywords:

Digoxin, Teratogenicity, Gestation

Abstract

Digoxin is used in thetreatment of chronic heart failureand/or atrial fibrillation and flutter(irregular heart rhythms caused by an electrical problem in theupper chambers of the heart).The aim of this study was to evaluate the teratogenic effects of Digoxin on pregnant rats and their fetuses. Pregnant albino rats (Rattusnorvegicus) were administrated daily oral doses of 0.3mg/kg of Digoxin from the5th- 19thday of gestation. The animals were sacrificed at the 20th day of gestation. Fetuses were removed from the uterus and evaluated for mortality rate, growth parameters, morphological and skeletal malformation as well as histological study of liver, kidney and brain. Results showed significant reduction in weight gain of pregnant rats and decreased placental weight of pregnant rats treated with Digoxin. Fetal growth retardation during gestational period was recorded. Hematomas and anomalies of limbswere noticed morphologically in the fetuses of the treated group. Fetal skeletal abnormalities were also recorded. These abnormalities included weak ossification of the skull bones roof. Histopathological studies of fetuses during gestation revealed presence of few megakaryoblasts in between hepatocytes in the liver, no histopathological alternations were observed in kidney of the treated group while in the brain tissue edema that was noticed in the meningesfollowing Digoxin administration. Digoxin pretreatment was able to increase the level of lipid peroxidation and it decreased the GSH level. Our findings suggest the need for great caution to handle Digoxin especially during pregnancy.

References

• Abrahamsson, C., Palmer, M., Ljung, B., Duker, G., Bäärnhielm, C., Carlsson, L. and Danielsson, B.(1994): Induction of rhythm abnormalities in the fetal rat heart. A tentative mechanism for the embryotoxic effect of the class III antiarrhythmic agent almokalant.Cardiovascular Research. 28, 337-344.

• Allonen, H., Kanto, J. and Ijsalo, E.(1976): The foeto-maternal distribution of

• Ban, Y., Konishi, R., Kawana, K., Nakatsuka, T., Fujii, T. and Manson, J. M. (1994): Embryotoxic effects of L-691,121, a class III antiarrhythmic agent, in rats. Archives of Toxicology. 69, 65-71.

• Bancroft, J.D. and Gamble, M. (2002): Theory and practice of histological techniques. 5th ed. Churchill Livingstone: London, UK 2002.

• Beutler, E., Duron, O. and Kelly, M.B. (1963): J. Lab Clin. Med., 61: 882.

• Bronsky, P. T., Johnston, M. C., and Sulik, K. K. (1986): Morphogenesis of hypoxiainduced cleft lip in CL/Fr mice. Journal of Craniofacial Genetics & Developmental Biology - Supplement. 2, 113-128.

• Burt, C. C. and Durbridge, J. (2009): Management of cardiac disease in pregnancy, Continuing Education in Anaesthesia, Critical Care and Pain, 9 (2): 44–47.

• Chen, E.Y., Fujinaga, M. and Giaccia, A.J. (1999): Hypoxic Microenvironment Within an Embryo Induces Apoptosis and Is Essential for Proper Morphological Development. Teratology. 60, 215-225.

• Danielsson, B.R. (1993): Developmental Toxicology Preclinical and Clinical Data in Retrospect. Tryckgruppen, Stockholm.Danielsson, B.R. (Malformations and Fetal Hypoxia Induced by Exaggerated Pharmacological Effects. In A. Sundwall, B. R. Danielsson, O. Hagberg, E. Lindgren, P. Sjöberg, and A. Viktor, Eds.), pp. 45-52. Tryckgruppen, Stockholm.

• Deinz, E., Dural, K. and Tuncay, P. (1995): Visualization of the fetal skeletal system by double staining with alizarin red and alcian blue. Gazi Medical Journal, 6: 55-58.

• Fantel, A. G. (1996): Reactive oxygen species in developmental toxicity: review and hypothesis. Teratology. 53, 196-217.

• Fantel, A. G., Person, R. E., Tumbic, R. W., Nguyen, T. D. and Mackler, B. (1995): Studies of mitochondria in oxidative embryotoxicity. Teratology. 52, 190-195.

• Fantel, A. G., Stamps, L. D., Tran, T. T., Mackler, B., Person, R. E., and Nekahi, N. (1999): Role of free radicals in the limb teratogenicity of L-NAME (N(G)-nitro-(L)-arginine methyl ester): a new mechanistic model of vasculardisruption. Teratology. 60, 151-160.

• Ferrero, S., Colombo, B.M.andRagni, N. (2003):Maternal arrhythmias during pregnancy.Arch Gynecol Obstet. 2004 May; 269 (4):244-53.

• Gutteridge, J. M. (1993). Free radicals in disease processes: a compilation of cause and consequence. Free Radical Research Communications. 19, 141-158.

• Joglar, J. A. and Page, R. L. (2014): Management of arrhythmia syndromes during pregnancy, Current Opinion in Cardiology. 29 (1): 36–44.

• Jequier, R., Deraedt, F., Plongeron, R. and Vannier, B. (1970): Pharmacology and toxicology of disopyramide [Fr.). Minerva Medica., 61 (71): 3689-93.

• K. L. Moore, The Developing Human, WB Saunder, Philadelphia, Pa, USA, 4th edition, 1988.

• Kalyanaraman, B., Konorev, E. A., Joseph, J., and Baker, J. E. (1995): Is free radical generation an important component of ischemia/reperfusion injury? Redox Report. 1, 181-184.

• Marks, T. A. and Terry, R. D. (1996): Developmental toxicity of ibutilidefumarate in rats after oral administration. Teratology. 54, 157-164.

• McClain, R. M. and Becker, B.A. (1975): Teratogenicity, foetal toxicity and placental transfer of lead nitrate in rats. Toxicol. Appl. Pharmacol., 931: 72-82.

• McCord, J. M. (1993): Human disease, free radicals, and the oxidant/antioxidant balance. Clinical Biochemistry. 26, 351-357.

• Naujoks, H. (1953): Der EinflusskurzfristigenSauerstoffmangles auf die Entwicklung des Huhnchens in den erstenfunfBruttagen. Beitr.Path.Anat. 113, 221-252.

• O’Rahilly, R.(2001): Human Embryology & Teratology, Wiley-Liss,New York, NY, USA, 3rd edition.

• Ohkawa, H., Ohhhishi, W., and Yagi, K. (1979): Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal.Biochem., 95 (2): 351-358.

• Poovala, V.S., Huang, H. and Salahudeen, A.K. (1999): Role of oxygen metabolites in organophosphate-bidrin-induced renal tubular cytotoxicity. J. Am. Soc. Neph., 10: 1746.

• Poovala, V.S., Kanji V.K., Tachikawa, H. and Salahundeen, A.K. (1998): Role of oxidant stress and antioxidant protection in acephate-induced renal tubular cytotoxicity. Toxicol. Sci., 46: 403.

• Rosińczuk, J., Całkosiński, I. (2015): Assessment of physical traits of rat offspring derived from mothers exposed to dioxin.Environ Toxicol. Pharmacol., 40 (2): 575-80.

• Rotmensch, H.H., Rotmensch, S. and Elkayam, U.(1987): Management of cardiac arrhythmias during pregnancy. Drugs. 33: 623–33.

• Satoh, K. (1978): Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. ClinicaChimicaActa., 90(1): 37-43.

• Schlegel, P. N., Chang, T. S. K. and Marshall, F. F. (1991): Antibiotics: potential hazards tomale fertility,†Fertility and Sterility. 55 (2): 235–242.

• Sherman, J.L. and Locke, R.V.(1960):Transplacental neonatal digitalis intoxication. Am. J. Cardio., 6: 834–7.

• Spence, S. G., Vetter, C. and Hoe, C. M. (1994): Effects of the class III antiarrhythmic, dofetilide (UK-68,798) on the heart rate of midgestation rat embryos, in vitro. Teratology. 49, 282-292.

• Taniguchi, M., Yasutake, A., Takedomi, K. and Inoue, K. (1999): Effects of N-nitrosodimethylamine (NDMA) on the oxidative status of rat liver. Arch. Toxicol., 73: 141.

• Webster, W.S., Brown-Woodman, P.D., Snow, M.D. and Danielsson, B.R. (1996): Teratogenic potential of almokalant, dofetilide, and d-sotalol: drugs withpotassium channel blocking activity. Teratology. 53, 168-175.

Downloads

Published

2016-07-02

How to Cite

El Ghareeb, A. E. W., Mostafa, S. A. E. R., Ali, H., & Al-harthi, T. J. (2016). Chemical and Biological Effects of Digoxin on Albino Rat Fetuses. Asian Journal of Applied Sciences, 4(3). Retrieved from https://www.ajouronline.com/index.php/AJAS/article/view/3794

Issue

Vol. 4 No. 3 (2016): June 2016

Section

Articles

License

  • Papers must be submitted on the understanding that they have not been published elsewhere (except in the form of an abstract or as part of a published lecture, review, or thesis) and are not currently under consideration by another journal published by any other publisher.
  • It is also the authors responsibility to ensure that the articles emanating from a particular source are submitted with the necessary approval.
  • The authors warrant that the paper is original and that he/she is the author of the paper, except for material that is clearly identified as to its original source, with permission notices from the copyright owners where required.
  • The authors ensure that all the references carefully and they are accurate in the text as well as in the list of references (and vice versa).
  • Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Attribution-NonCommercial 4.0 International that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
  • Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
  • Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
  • The journal/publisher is not responsible for subsequent uses of the work. It is the author's responsibility to bring an infringement action if so desired by the author.

Most read articles by the same author(s)