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Abstract Title:

Increases in discontinuous rib cartilage and fused carpal bone in rat fetuses exposed to the teratogens, busulfan, acetazolamide, vitamin A, and ketoconazole.

Abstract Source:

Hum Exp Toxicol. 2010 Jun;29(6):439-50. Epub 2010 Mar 17. PMID: 20237176

Abstract Author(s):

T Dodo, K Uchida, T Hirose, T Fukuta, C Kojima, I Shiraishi, E Kato, T Horiba, H Mineshima, Y Okuda, M Maeda, N Katsutani, K Hirano, T Aoki

Article Affiliation:

Planning&Coordination Department, Biopharmaceutical Assessments Core Function Unit, Eisai Co., Tokodai Tsukuba-shi, Ibaraki, Japan. t-dodo@hhc.eisai.co.jp

Abstract:

Skeletal changes induced by treatment of pregnant rats with four potent teratogens, busulfan, acetazolamide, vitamin A palmitate, and ketoconazole, were evaluated using Alizarin Red S and Alcian Blue double-staining to investigate the relationship between drug-induced skeletal malformations and cartilaginous changes in the fetuses. Pregnant rats (N = 8/group) were treated once or twice between gestation days (GDs) 10 to 13 with busulfan at doses of 3, 10, or 30 mg/kg; acetazolamide at 200, 400, or 800 mg/kg; vitamin A palmitate at 100,000, 300,000, or 1,000,000 IU/kg; or ketoconazole at doses of 10, 30, or 100 mg/kg. Uterine evaluations and fetal external and skeletal examinations were conducted on GD 20. Marked skeletal abnormalities in ribs and hand/forelimb bones such as absent/ short/bent ribs, fused rib cartilage, absent/fused forepaw phalanx, and misshapen carpal bones were induced at the mid- and high-doses of busulfan and acetazolamide and at the high-dose of vitamin A palmitate and ketoconazole. Increased incidences of discontinuous rib cartilage (DRC) and fused carpal bone (FCB) were observed from the low- or mid-dose in the busulfan and acetazolamide groups, and incidences of FCB were increased from the mid-dose in the vitamin A palmitate and ketoconazole groups. Therefore, DRC and FCB were detected at lower doses than those at which ribs and hand/forelimb malformations were observed in the four potent teratogens.

Study Type : Animal Study

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Sayer Ji
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