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Protective Effects of L-Carnitine on Growth and Cardiac Function in High-Glucose-Exposed Zebrafish Embryos
Abstract
Diabetes mellitus is a chronic metabolic disorder, and maternal hyperglycaemia during pregnancy increases the risk of fetal developmental complications. This study aimed to evaluate the protective role of L-carnitine against glucose-induced embryotoxicity in zebrafish (Danio rerio). Fertilized embryos were exposed to 5% glucose with or without L-carnitine supplementation (50 or 100 uM). Developmental outcomes including survival, hatching, malformations, body length, and heart rate were assessed using microscopy and analyzed by ANOVA and Kaplan–Meier survival curves. High glucose significantly reduced survival (hazard ratio = 6.86; p < 0.0001), delayed hatching (median hatching time 84 vs. 60 hpf; HR = 0.17, 95% CI = 0.08–0.39; p < 0.0001), and induced growth retardation and bradycardia (p < 0.0001). L-carnitine did not rescue survival or hatching but partially ameliorated growth impairment (p < 0.05) and restored heart rate in a dose-dependent manner, with 100 uM supplementation approaching control values (p < 0.001). Morphological abnormalities such as yolk sac edema and spinal curvature remained present but less severe with co-treatment. In conclusion, L-carnitine confers partial protective effects on growth and cardiac function under hyperglycaemic stress, although it does not prevent early lethality.
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Adeva-Andany, M. M., Calvo-Castro, I., Fernández-Fernández, C., Donapetry-García, C., & Pedre-Piñeiro, A. M. (2017). Significance of L -carnitine for human health. IUBMB Life, 69(8), 578–594. https://doi.org/10.1002/iub.1646
Capiotti, K. M., Antonioli, R., Kist, L. W., Bogo, M. R., Bonan, C. D., & Da Silva, R. S. (2014). Persistent impaired glucose metabolism in a zebrafish hyperglycemia model. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 171, 58–65. https://doi.org/10.1016/j.cbpb.2014.03.005
Chakraborty, C., Sharma, A. R., Sharma, G., & Lee, S.-S. (2016). Zebrafish: A complete animal model to enumerate the nanoparticle toxicity. Journal of Nanobiotechnology, 14(1), 65. https://doi.org/10.1186/s12951-016-0217-6
Gu, Q., Ali, S. F., & Kanungo, J. (2021). Effects of acetyl L?carnitine on zebrafish embryos: Phenotypic and gene expression studies. Journal of Applied Toxicology, 41(2), 256–264. https://doi.org/10.1002/jat.4041
Hong, T., Park, J., Song, G., & Lim, W. (2024). Brief guidelines for zebrafish embryotoxicity tests. Molecules and Cells, 47(8), 100090. https://doi.org/10.1016/j.mocell.2024.100090
International Diabetes Federation. (2021). IDF Diabetes Atlas (10th edn). International Diabetes Federation. https://diabetesatlas.org/atlas/tenth-edition/
Kalra, S., Gupta, Y., Kalra, B., & Singla, R. (2015). Use of oral anti-diabetic agents in pregnancy: A pragmatic approach. North American Journal of Medical Sciences, 7(1), 6. https://doi.org/10.4103/1947-2714.150081
Kanungo, J., Cuevas, E., Ali, S. F., & Paule, M. G. (2012). L-Carnitine rescues ketamine-induced attenuated heart rate and MAPK (ERK) activity in zebrafish embryos. Reproductive Toxicology (Elmsford, N.Y.), 33(2), 205–212. https://doi.org/10.1016/j.reprotox.2011.10.004
Li, Y., Chen, Q., Liu, Y., Bi, L., Jin, L., Xu, K., & Peng, R. (2022). High glucose-induced ROS-accumulation in embryo-larval stages of zebrafish leads to mitochondria-mediated apoptosis. Apoptosis, 27(7–8), 509–520. https://doi.org/10.1007/s10495-022-01731-2
Longnus, S. L., Wambolt, R. B., Barr, R. L., Lopaschuk, G. D., & Allard, M. F. (2001). Regulation of myocardial fatty acid oxidation by substrate supply. American Journal of Physiology-Heart and Circulatory Physiology. https://doi.org/10.1152/ajpheart.2001.281.4.H1561
Ma, Y., Wang, Q., Ghonimy, A., Chen, Y., Guo, Z., Zhang, D., & Wang, G. (2020). The improving effect of l-carnitine on larvae quality in early life stage of zebrafish (Danio rerio). Aquaculture, 525, 735222. https://doi.org/10.1016/j.aquaculture.2020.735222
Ogurtsova, K., Da Rocha Fernandes, J. D., Huang, Y., Linnenkamp, U., Guariguata, L., Cho, N. H., Cavan, D., Shaw, J. E., & Makaroff, L. E. (2017). IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Research and Clinical Practice, 128, 40–50. https://doi.org/10.1016/j.diabres.2017.03.024
Sawicka, A. K., Renzi, G., & Olek, R. A. (2020). The bright and the dark sides of L-carnitine supplementation: A systematic review. Journal of the International Society of Sports Nutrition, 17(1), 49. https://doi.org/10.1186/s12970-020-00377-2
Schulz, H. (1994). Regulation of Fatty Acid Oxidation in Heart. The Journal of Nutrition, 124(2), 165–171. https://doi.org/10.1093/jn/124.2.165
Singh, A., Castillo, H. A., Brown, J., Kaslin, J., Dwyer, K. M., & Gibert, Y. (2019). High glucose levels affect retinal patterning during zebrafish embryogenesis. Scientific Reports, 9(1), 4121. https://doi.org/10.1038/s41598-019-41009-3
Thompson, E., Hensley, J., & Taylor, R. S. (2024). Effect of High Glucose on Embryological Development of Zebrafish, Brachyodanio, Rerio through Wnt Pathway. International Journal of Molecular Sciences, 25(17), 9443. https://doi.org/10.3390/ijms25179443
Tinker, S. C., Gilboa, S. M., Moore, C. A., Waller, D. K., Simeone, R. M., Kim, S. Y., Jamieson, D. J., Botto, L. D., Fisher, S. C., Reefhuis, J., & the National Birth Defects Prevention Study. (2021). Modification of the association between diabetes and birth defects by obesity, National Birth Defects Prevention Study, 1997–2011. Birth Defects Research, 113(14), 1084–1097. https://doi.org/10.1002/bdr2.1900
Virmani, M. A., & Cirulli, M. (2022). The Role of l-Carnitine in Mitochondria, Prevention of Metabolic Inflexibility and Disease Initiation. International Journal of Molecular Sciences, 23(5), Article 5. https://doi.org/10.3390/ijms23052717
Westerfield, M. (2007). The Zebrafish Book: A guide for the laboratory use of zebrafish (Danio rerio). https://cir.nii.ac.jp/crid/1370283694361132063
Yoon, C.-Y., Chon, K., Vasamsetti, B. M. K., Hwang, S., Park, K.-H., & Kyung, K. S. (2024). Developmental Toxicity and Teratogenic Effects of Dicarboximide Fungicide Iprodione on Zebrafish (Danio rerio) Embryos. Fishes, 9(11), 425. https://doi.org/10.3390/fishes9110425
DOI: https://doi.org/10.14421/biomedich.2025.142.879-885
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