Vitamin B6 antagonists alter the function and ultrastructure of mice endothelial cells.
Vitamin B6, is necessary for normal membrane function and stability. Here we studied both the function and ultrastructure of aortic and arterial endothelial cells (ECs) in vitamin B6 deficient mice induced by vitamin B6 antagonists, 4-deoxypyridoxine x HCl (dPN x HCl), and isonicotinylhydrazide (INH). Mice were fed with normal laboratory chow and divided into three groups according to their drinking water. Mice in group I had distilled water and served as a control; group II had 0.1 mg dPN x HCl/mL H2O; and group III had 0.4 mg INH/mL H2O. After 5 mo, plasma concentrations of B6 vitamers pyridoxal-5'-phosphate (PLP) and pyridoxal (PL) were analyzed by HPLC. With the arachidonic acid (AA) as a precursor, prostacyclin (PGI2) production from ECs assayed by thin-layer chromatography (TLC) was used as an indicator of endothelial function. Aorta and arteriole from foot pad were removed, stained with osmium tetraoxide, and examined under transmission electron microscopy (TEM) to study the ultrastructure of ECs. The results showed that plasma concentrations of PLP, PL, and total B6 were the lowest for mice fed with INH. followed by that with dPN x HCl, compared with that of control. PGI2 production was paralleled with the plasma vitamin B6 status, with the lowest level for INH, followed by the dPN-treated group. Abnormalities in the ultrastructure of ECs were found in both dPN x HCl and INH groups, including cells detached from underlying elastic tissue, with prominent pinocytotic vesicles and swelling and/or indistinct cristae of mitochondria. These results suggest that vitamin B6 antagonists induce a deficient status that alters the function and the ultrastructure of ECs detrimental to vascular disease.
Chang
S J
SJ
Departrment of Biology, National Cheng Kung University, Taiwan. sjchang@mail.ncku.edu.tw
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer / Q000379:methods; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D011464:Epoprostenol / Q000096:biosynthesis; D007538:Isoniazid / Q000031:analogs & derivatives / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D008854:Microscopy, Electron / Q000379:methods; D011730:Pyridoxal / Q000097:blood; D011732:Pyridoxal Phosphate / Q000097:blood; D011736:Pyridoxine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology*; D011897:Random Allocation; D026681:Vitamin B 6 Deficiency / Q000139:chemically induced*
D011730:Pyridoxal; D011732:Pyridoxal Phosphate; C004675:4-deoxypyridoxine; D011464:Epoprostenol; D011736:Pyridoxine; D007538:Isoniazid