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Nahedh Faris1 
, Doaa Ismael2 , Shatha Shaker1 , Raghad Saeed1 , Anas Al-Hayawi1 , Rasha AlMoussawi *3
, Doaa Ismael2 , Shatha Shaker1 , Raghad Saeed1 , Anas Al-Hayawi1 , Rasha AlMoussawi *3
1- Department of Biology, College of Education for Pure Sciences, Tikrit University, Tikrit, Iraq. (34001),
2- Cancer Research Department, Iraqi Centre for Cancer and Medical Genetic Research, Mustansiriyah University, Baghdad, Iraq. (10011)
3- Child Protection Officer, General Directorate, Department of Counselling & Guidance, Ministry of Education and Higher Education, Beirut, Lebanon. and Department of Pharmacy, Lebanese International University, Beirut, Lebanon. (1001), ,RMoussawi@MEHE.gov.lb
2- Cancer Research Department, Iraqi Centre for Cancer and Medical Genetic Research, Mustansiriyah University, Baghdad, Iraq. (10011)
3- Child Protection Officer, General Directorate, Department of Counselling & Guidance, Ministry of Education and Higher Education, Beirut, Lebanon. and Department of Pharmacy, Lebanese International University, Beirut, Lebanon. (1001), ,
Abstract: (32 Views)
Background: The developmental safety of repaglinide during pregnancy remains inadequately characterized. This study evaluated the effects of prenatal repaglinide exposure on fetal viability, growth, skeletal maturation, and hepatic and pulmonary development in Wistar rats.
Materials and Methods. Pregnant rats were allocated to 4 groups (15 dams/litters per group) and received vehicle or repaglinide at 0.3, 1.0, or 3.0 mg/kg/day by oral gavage from gestational day (GD) 6 to GD18. Fetuses were collected on GD19; the dam/litter was the experimental unit, and fetal values were averaged within each litter. Fetal growth, post-implantation loss, skeletal ossification, histopathology, morphometry, immunohistochemistry, and selected biochemical markers were evaluated.
Results: Repaglinide was associated with dose-related developmental toxicity. In the high-dose group versus control, post-implantation loss increased from 5.8% to 33.5%, while fetal weight decreased from 2.38 ± 0.15 to 1.85 ± 0.24 g. Delayed skeletal ossification, hepatic microvesicular steatosis, glycogen depletion, reduced Ki-67 expression, and increased cleaved caspase-3 immunoreactivity were observed. Distal lung structural complexity was reduced, with radial alveolar count decreasing from 8.2 ± 0.9 to 5.1 ± 0.7 and mean linear intercept increasing from 46.1 ± 3.8 to 70.5 ± 5.6 µm (P < 0.001). Pro-SPC immunoreactivity was also reduced. Values are litter means (n = 15 litters/group).
Conclusion: Prenatal repaglinide exposure was associated with dose-dependent fetotoxicity and delayed hepatic, pulmonary, and skeletal maturation indices in non-diabetic Wistar rats under the conditions tested. These findings do not establish clinical risk in human pregnancy; studies in diabetic pregnancy models are required before any clinical extrapolation.
Materials and Methods. Pregnant rats were allocated to 4 groups (15 dams/litters per group) and received vehicle or repaglinide at 0.3, 1.0, or 3.0 mg/kg/day by oral gavage from gestational day (GD) 6 to GD18. Fetuses were collected on GD19; the dam/litter was the experimental unit, and fetal values were averaged within each litter. Fetal growth, post-implantation loss, skeletal ossification, histopathology, morphometry, immunohistochemistry, and selected biochemical markers were evaluated.
Results: Repaglinide was associated with dose-related developmental toxicity. In the high-dose group versus control, post-implantation loss increased from 5.8% to 33.5%, while fetal weight decreased from 2.38 ± 0.15 to 1.85 ± 0.24 g. Delayed skeletal ossification, hepatic microvesicular steatosis, glycogen depletion, reduced Ki-67 expression, and increased cleaved caspase-3 immunoreactivity were observed. Distal lung structural complexity was reduced, with radial alveolar count decreasing from 8.2 ± 0.9 to 5.1 ± 0.7 and mean linear intercept increasing from 46.1 ± 3.8 to 70.5 ± 5.6 µm (P < 0.001). Pro-SPC immunoreactivity was also reduced. Values are litter means (n = 15 litters/group).
Conclusion: Prenatal repaglinide exposure was associated with dose-dependent fetotoxicity and delayed hepatic, pulmonary, and skeletal maturation indices in non-diabetic Wistar rats under the conditions tested. These findings do not establish clinical risk in human pregnancy; studies in diabetic pregnancy models are required before any clinical extrapolation.
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The Iranian Journal of Toxicology
Arak University of Medical Sciences in collaboration with the Iranian Society of Toxicology
Website: http://ijt.arakmu.ac.ir
Email: tox.journal@gmail.com
