Evaluation of Sodium Butyrate-Induced Cellular and Ultrastructural Changes in K562 Cells Using Scanning and Transmission Electron Microscopy

Abstract

Sodium butyrate (NaB) is an established inducer of erythroid differentiation and fetal hemoglobin production in K562 cells. However, its cellular and ultrastructural effects across different concentrations and exposure periods require further characterization. This study evaluated the cellular and ultrastructural effects of NaB on human erythroleukemia K562 cells using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). K562 cells were exposed to 0.01, 0.1, and 1.0 mM NaB for 1, 3, and 7 days. Untreated cells served as controls, while 1 µM hydroxyurea (HU) and a combination of 1 µM HU with 0.1 mM NaB were included for comparison. SEM assessed cell shape, size, microvilli, surface folds, flattening, and surface irregularities, whereas TEM evaluated plasma and nuclear membrane integrity, chromatin organization, mitochondria, cytoplasmic organization, and vacuolation. NaB produced concentration- and time-dependent morphological alterations. Exposure to 0.01 mM NaB produced relatively limited surface changes, although cytoplasmic vacuolation increased with prolonged exposure. At 0.1 mM, cells demonstrated progressive flattening, loss of microvilli and surface folds, increased cytoplasmic vacuolation, and alterations in nuclear organization. The most pronounced abnormalities occurred at 1.0 mM NaB, including cellular flattening and distortion, loss of microvilli, surface irregularities, plasma membrane disruption, severe cytoplasmic vacuolation, and loss of nuclear membrane integrity. HU and the NaB-HU combination also produced morphological changes, although intracellular structures were relatively preserved during early exposure periods. The findings demonstrate that NaB induces concentration- and exposure-dependent cellular and ultrastructural changes in K562 cells, with the highest concentration showing the clearest evidence of cellular injury. These findings provide morphological evidence for distinguishing differentiation-associated responses from concentration-dependent cytotoxic effects of NaB.

Keywords: Sodium Butyrate; K562 Cells; Erythroid Differentiation; Fetal Hemoglobin; Scanning Electron Microscopy; Transmission Electron Microscopy; Ultrastructure; Cellular Morphology; Hydroxyurea; Cytotoxicity.

DOI: 10.7176/JMPB/76-05

Publication date: August 31^st 2026