Infant hypervitaminosis A causes severe anemia and thrombocytopenia: evidence of a retinol-dependent bone marrow cell growth inhibition.
Vitamin A is a pivotal biochemical factor required for normal proliferation and differentiation as well as for specialized functions, such as vision. The dietary intake of 1500 IU/day is recommended in the first year of life. Here, we report the case of an infant who had been given 62 000 IU/day for 80 days. The infant showed several clinical signs of retinol intoxication, including severe anemia and thrombocytopenia. Bone marrow showed a remarkably reduced number of erythroid and megakaryocytic cells. The interruption of vitamin A treatment was immediately followed by clinical and biochemical recovery. To clarify whether the effects of retinol are due to a direct action on bone marrow cell proliferation, we investigated the activity of retinol (both the drug and the pure molecule) on the growth of K-562, a multipotent hematopoietic cell line, and on bone marrow mesenchymal stem cells. We observed that vitamin A strongly inhibited the proliferation of the cells at concentrations similar to those reached in vivo. Subsequent biochemical analyses of the cell cycle suggested that the effect was mediated by the up-regulation of cyclin-dependent kinase inhibitors, p21(Cip1) and p27(Kip1). These are the first findings to demonstrate that infant hypervitaminosis A causes a severe anemia and thrombocytopenia and that this is probably due to the direct effect of the molecule on the growth of all bone marrow cellular components. Our data also suggest potential bone marrow functional alterations after excessive vitamin A intake because of emerging social habits.
Perrotta
Silverio
S
Department of Pediatrics, Department of Biochemistry and Biophysics F. Cedrangolo, Second University of Naples, Via S. Andrea delle Dame 4, 80138 Naples, Italy. silverio.perotta@unina2.it
Nobili
Bruno
B
Rossi
Francesca
F
Criscuolo
Maria
M
Iolascon
Achille
A
Di Pinto
Daniela
D
Passaro
Irene
I
Cennamo
Lucia
L
Oliva
Adriana
A
Della Ragione
Fulvio
F
D000740:Anemia / Q000209:etiology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000187:drug effects; D006801:Humans; D006986:Hypervitaminosis A / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D007223:Infant; D020014:K562 Cells / Q000187:drug effects; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects; D013921:Thrombocytopenia / Q000209:etiology* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D014801:Vitamin A / Q000494:pharmacology / Q000502:physiology / Q000633:toxicity
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D025521:Tumor Suppressor Proteins; D014801:Vitamin A; D050760:Cyclin-Dependent Kinase Inhibitor p27