The effect of favipiravir on histone deacetylase (HDAC) enzyme activity in administered to human primary chondrocyte cultures and an evaluation of its relationship with inflammation

Abstract

Aim: The existing literature is inconclusive about the in vitro cytotoxicity of favipiravir (FVP) administered with valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, and the effects of FVP on HDAC activity and inflammation markers. This study aimed to evaluate the in vitro effects of FVP administered to human primary chondrocyte cultures by investigating its effects on HDAC enzyme activity and interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) gene expression levels.

Methods: Primary chondrocyte cultures were prepared using tissues obtained from operated cases. Untreated primary cell culture samples constituted the control group. Cultures administered with FVP were the study group. Analyses were performed simultaneously on the samples in both groups at the end of 0, 24, 48, and 72 h. The surface morphology of the cells and the extracellular matrix were evaluated using an inverted light microscope. Cell viability, proliferation, and cytotoxicity evaluations were investigated using MTT analysis and acridine orange/propidium iodide stains. Commercial kits were used to measure HDAC enzyme activity and IL-6, IL-10, and TNF-α expression levels. An enzyme-linked immunosorbent assay was performed to evaluate the cell inflammatory responses. The data were analyzed statistically.

Results: FVP did not change the HDAC activity of the primary cultures; however, it produced a proinflammatory response by increasing levels of TNF-α in the cells and an anti-inflammatory response by increasing levels of IL-10.

Conclusions: FVP-induced proinflammatory responses in primary chondrocytes are independent of HDAC activity, with potential resistance to inflammatory responses through an additional anti-inflammatory response.