Embryonic exposure to acetyl-L-carnitine protects against valproic acid-induced cardiac malformation in zebrafish model

Embryonic exposure to acetyl-L-carnitine protects against valproic acid-induced cardiac malformation in zebrafish model

Worldwide, estimated counts of about 7.9 million children are born with serious birth defects. In addition to genetic factors, prenatal exposure to drugs and environmental toxicants represents a major contributing factor to congenital malformations. In earlier investigation, we explored cardiac malf...

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Bibliographic Details
Published in:Amino acids Vol. 55; no. 5; pp. 619 - 638
Main Authors: Rajesh, Venugopalan, Kokilavani, Annadurai, Jayaseelan, Subramanian, Gomathi, Swaminathan, Vishali, Korrapati, Kumudhavalli, Manni Venkatachari
Format: Journal Article
Language:English
Published: Vienna Springer Vienna 01-05-2023
Springer Nature B.V
Subjects:
Acetyl-L-carnitine
Analytical Chemistry
Apoptosis
Biochemical Engineering
Biochemistry
Biomedical and Life Sciences
Birth defects
Carnitine
Congenital defects
Danio rerio
Edema
Embryos
Energy metabolism
Exposure
Fatty acids
Fertilization
Genetic factors
Heart
Homeostasis
Life Sciences
Metabolism
Morphology
Neurobiology
Original Article
Oxidative metabolism
Prenatal experience
Prenatal exposure
Proteomics
Recovery of function
Toxicants
Valproic acid
Zebrafish
Acetyl-L-carnitine
Zebrafish
Cardioprotective
Cardiac malformation
Valproic acid
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Summary:Worldwide, estimated counts of about 7.9 million children are born with serious birth defects. In addition to genetic factors, prenatal exposure to drugs and environmental toxicants represents a major contributing factor to congenital malformations. In earlier investigation, we explored cardiac malformation caused by valproic acid (VPA) during early developing stages of zebrafish. Since heart depends on mitochondrial fatty acid oxidative metabolism for energy demands in which carnitine shuttle has a major role, the present study aimed to investigate the effect of acetyl-L-carnitine (AC) against VPA-induced cardiac malformation in developing zebrafish. Initially, AC was subjected to toxicological evaluation, and two micromolar concentrations (25 µM and 50 µM) were selected for evaluation. A sub-lethal concentration of VPA (50 µM) was selected to induce cardiac malformation. The embryos were grouped and the drug exposures were made at 2.5 h post-fertilization (hpf). The cardiac development and functioning was monitored. A progressive decline in cardiac functioning was noted in group exposed to VPA 50 µM. At 96 hpf and 120 hpf, the morphology of heart was severely affected with the chambers which became elongated and string-like accompanied by histological changes. Acridine orange staining showed accumulation of apoptotic cells. Group exposed to VPA 50 µM with AC 50 µM showed a significant reduction in pericardial sac edema with morphological, functional and histological recovery in developing heart. Moreover, reduced number of apoptotic cells was noted. The improvement with AC might be due to restoration of carnitine homeostasis for cardiac energy metabolism in developing heart.
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ISSN:0939-4451
1438-2199
DOI:10.1007/s00726-023-03256-7