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Effects of Licorice on Embryonic and Fetal Development in Rats  

Shin Sunhee (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University)
Jang Ja Young (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University)
Baek In-Jeoung (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University)
Yon Jung-Min (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University)
Nam Sang-Yoon (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University)
Yun Young Won (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University)
Cho Dae-Hyun (Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration)
Kim Soon-Sun (Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration)
Rhee Gyu-Seek (Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration)
Kwack Seung-Jun (Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration)
Kim Yun-Bae (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University)
Publication Information
Toxicological Research / v.21, no.4, 2005 , pp. 325-332 More about this Journal
Abstract
The developmental toxicity of water extract of licorice (Glycyrrhiza glabra) was evaluated in rats. Licorice extract (500, 1,000 or 2,000 mg/kg) was dissolved in drinking water and orally administered to male rats from 9 weeks before mating to the day of copulation, and to females from 2 weeks before mating to gestational day 19. On gestational day 20, the animals were sacrificed for Cesarian section, and maternal and fetal abnormalities were examined. Licorice extract neither induce clinical signs, nor affect the body weight gain, feed and water intake, estrous cycle, copulation and fertility rates, blood $17\beta-estradiol$ level and organ weights of dams. Also, the implantation and development including body weights, absorption and death of embryos and fetuses were not influenced by in utero exposure to licorice. In addition, there were no increases in external, visceral and skeletal abnormalities of fetuses. Taken together, it is suggested that no observed adverse effect level of licorice extract is higher than 2,000 mg/kg, and that long-term in utero exposure to licorice might not cause developmental toxicities of embryos and fetuses.
Keywords
Glycyrrhiza glabra (licorice); Glycyrrhizin (glycyrrhizic acid); Developmental toxicity; Safety;
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1 Davis, E.A. and Morris, D.J. (1991): Medicinal uses of licorice through the millennia: the good and plenty of it. Mol. Cell. Endocrinol., 78, 1-6   DOI   PUBMED   ScienceOn
2 Dinah, V., Parums, F.G., Corsi, F.M. and Giacanelli, M. (1999): Latrogenic worsening of hypokalemia and neuromuscular paralysis associated with the use of glucose solutions for potassium replacement in a young woman with licorice intoxication and furosemide abuse. Acad. Emerg. Med., 6, 960-964   DOI   ScienceOn
3 Endo, Y. (1994): The immunoactive therapy for patients with positive HIV using glycyrrhizin. Inf. Conf. AIDS, 10, 218
4 Epstein, M.T., Espiner, E.A., Donald, R.A. and Hughes, H. (1977): Liquorice toxicity and the renin-angiotensin-aldosterone axis in man. Br. Med. J., 1, 209-210   DOI
5 Farese, R.V., Jr., Biglieri, E.G. and Shackleton, C.H. (1991): Licorice-induced hypermineralocorticoidism. N. Engl. J. Med., 325,1223-1227   DOI
6 Koh, S.-B., Seo, M.-Y., Jeong, J.-H., Lee, J.-Y., Kang, M.-H., Kim, D.-Y. and Sung, H.-J. (2005): 13-Week oral toxicity study of licorice root in F344 rats. Lab. Anim. Res., in press
7 Mori, K. (1989): Effects of glycyrrhizin in hemophilia patients with HIV infection. Tohoku J. Exp. Med., 158, 25-35   DOI   ScienceOn
8 Numazaki, K. (1994): Effect of glycyrrhizin in children with liver dysfunction associated with cytomegalovirus infection. Tohoku J. Exp. Med., b, 147-153   DOI
9 Satoru, T., Astushi, T. and Kunio, K. (1986): Toxicological studies on biological effects of the herbals drug extracts in rats and mice. Yakugaku Zasshi, 106, 671-686   DOI
10 Spinks, E.A. and Fenwick, G.R. (1990): The determination of glycyrrhizin in selected UK liquorice products. Food Addit. Contam., 7, 769-778   DOI   ScienceOn
11 식품의약품안전청 (1999): 의약품등의 독성시험기준 (고시 제 1999-61호). 식품의약품안전청, 서울
12 Baker, M.E. (1994): Licorice and enzymes other than 11 beta-hydroxysteroid dehydrogenase: an evolutionary perspective. Steroids, 59, 136-141   DOI   PUBMED   ScienceOn
13 Ikegarri, N. (1989): Clinical evaluation of glycyrrhizin on the HIV-infected asymptomatic hemophiliac patients in Japan. Int. Conf. AIDS, 5, 401
14 Imaizumi, M. (1994): Effect of long term therapy with glycyrrhizin for HIV infection in a hemophilia patient. Int. Conf. AIDS, 10, 224
15 Nielsen, I. and Pedersen, R.S. (1984): Life-threatening hypokalaemia caused by liquorice ingestion. Lancet, 1, 1305   DOI   ScienceOn
16 Inouye, M. (1976): Differential staining of cartilage and bone in fetal mouse skeleton by alcian red and alizarin red S. Congenit. Anom., 16, 171-173
17 Barrella, M., Lauria, G., Quatrale, R. and Paolino, E. (1991): Hypokaliemic rhabdomyolysis associated with liquorice ingestion: report of an atypical case. Ital. J. Neurol. Sci., 18, 217-220   DOI   ScienceOn
18 Guyant, L. (1988): Canine vaginal cytology. Vet. Technician, 9, 513-520
19 Haberer, J.P., Jouve, P., Bedoc,k B. and Bazin, P.E. (1984): Severe hypokalaemia secondary to overindulgence in alcohol-free 'pastis'. Lancet, 1, 575-577   DOI   ScienceOn
20 Chamberlain, J.J. and Abolnik, I.Z. (1997): Pulmonary edema following a licorice binge. West. J. Med., 167, 184-185
21 Miyaji, C. (1994): The effect of glycyrrhizin in mice infected with murine retrovirus. I. Prevention of the progression of the disease. Int. Conf. AIDS, 10, 130
22 Mori, K. (1994): Two cases of AIDS associated with hemophilia A, treated effectively by the concomitant use of SNMC (strong Dose GL) and ddl. Int. Conf. AIDS, 10, 205
23 Ito, M. (1987): The inhibitory effect of glycyrrhizin on the in vitro infectivity and cytopathic activity of HIV. Antiviral Res., 7,127-137   DOI   ScienceOn
24 Schutte, A.P. (1967): Canine vaginal cytology. I. Technique and cytological morphology. J. Small Anim. Pract., 8, 301-306   DOI   ScienceOn
25 Biglieri, E.G. (1991): Spectrum of mineralo- corticoid hypertension. Hypertension, 17, 251-261   DOI
26 Ito, M. (1988): Mechanism of inhibitory effect of glycyrrhizin on replication of human immunodeficiency virus. Antiviral Res., 10, 289-298   DOI   ScienceOn
27 Mori, K. (1990): Effects of high dose glycyrrhizin on hemophilia patient with HIV infection. Int. Conf. AIDS, 6, 394
28 Armanini, D., Bonanni, G. and Palermo, M. (1999): Reduction of serum testosterone in men by licorice. N. Engl. J. Med., 341, 1158   DOI   ScienceOn
29 Mori, K. (1990): Effects of high dose glycyrrhizin on hemophilia patient with HIV infection. Int. Conf. AIDS, 6, 394
30 Wilson, J.G. (1965): Methods for administering agents and detecting malformations in experimental animals in Teratology. Principles and Techniques. University of Chicago Press, Chicago, pp. 262-277
31 Walker, B.R. and Edwards, C.R. (1994): Licorice-induced hypertension and syndromes of apparent mineralocorticoid excess. Endocrinol. Metab. Clin. North. Am., 23, 359-377
32 Hirabyashi, K. (1991): Antiviral activities of glycyrrhizin and its modified compounds against human immunodeficiency virus type 1 and herpes simplex virus type 1 in vitro. Chem. Pharm. Bull. (Tokyo), 39, 112-115   DOI
33 Nishimura, K.A. (1974): Microdissection method for detecting thoracic visceral malformations in mouse and rat fetuses. Congenit. Anom., 14, 23-40
34 Schambelan, M. (1994): Licorice ingestion and blood pressure regulating hormones. Steroids, 59, 127-130   DOI   PUBMED   ScienceOn
35 Watanabe, H. (1994) The effect of glycyrrhizin in mice infected with murine retrovirus. II. Inhibitory effects on proliferation and function of lymphoid cells. Int. Conf. AIDS, 10, 130
36 이중달 (1986): 진단세포학, 대학서림, 서울, pp. 613-651
37 Armanini, D., Lewicka, S. and Pratesi, C. (1996): Further studies on the mechanism of the mineralocorticoid action of licorice in humans. J. Endocrinol. Invest., 19, 624-629   DOI
38 Naskashima, H. (1987): A new anti-human immunodeficiency virus substance, glycyrrhizin with reverse transcriptase inhibitory activity by chemical modification. Japan J. Cancer Res., 78, 767-771