Investigation of the effect of dipyrone on cells isolated from intervertebral disc tissue

Abstract

The present study aimed to evaluate the effects of dipyrone, an indispensable analgesic, anti-pyretic and anti-spasmodic used in emergency departments, on nucleus pulposus and annulus fibrosus cells in vitro . After surgical biopsy, primary cell cultures were prepared from intact intervertebral disc tissues. Dipyrone was administered to the cultures in the experimental groups except for the control group. The data obtained were statistically evaluated. The proliferation was identified to be suppressed via MTT analysis. The gene expression profile of the intervertebral disc cells in the dipyrone-treated groups was significantly changed. The expression of chondroadherin, cartilage oligo matrix protein, interleukin-1β and metalloproteinase (MMP)-19 genes were decreased, but MMP-13 and MMP-7 genes expressions were increased, as determined via reverse transcription-quantitative PCR. AO/PI staining revealed that no apoptotic or other type of cell death was detectable after administration of dipyrone does not mean that the drug is innocuous. The occurrence of cellular senescence and/or the halt of cell proliferation may also be important mechanisms underlying the adverse inhibitory effects of dipyrone. Therefore, prior to administering dipyrone in clinical practice, all possible adverse effects of this drug should be considered.

Toxicity of the acetyl‑para‑aminophenol group of medicines to intact intervertebral disc tissue cells

“…Therefore, the results obtained from assays using animal tissues may diverge from those using human tissues, which may result in misleading outcomes (6)(7)(8)(9)(10)(11)13,14). Commercial cell lines are known to comprise only a single type of cell, and there are no complicated coordination mechanisms in the microenvironment of the cells (6)(7)(8)(9)(10)(11)13,14). They do not have the same genotypic and/or phenotypic characteristics as in the human body; therefore, the results of studies using cell lines may also be misleading (6)(7)(8)(9)(10)(11)13,14).…”

“…CHAD, as a constantly expressed NP-specific marker, is secreted from NP/AF cells serving a key role in the organization of ECM and contributes toward the formation of a healthy microenvironment in the IVD tissue. ECM aid in keeping cells and tissues together and supports the cell structure and function in the continuity of cell viability and migration of cells (6)(7)(8). Cell-matrix interactions are regulated by proteolytic enzymes, including MMP-7, MMP-13 and MMP-19 (6)(7)(8).…”

“…Microphotographs of cell structures were obtained ( Fig. 1; second lane), and the images were evaluated using the CytoVision ® v 7.0 (DM6000B; Leica Microsystems GmbH) capture station imaging program (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

“…thermofisher.com/order/genome-database/). Relative quantification (RQ) was performed according to the average Ct values obtained using the b-actin (Hs01060665_g1) gene as an endogenous control and the control group as a calibrator (7,8). Using this method, the difference in gene expression between the control group and experimental groups was determined as a fold-change.…”

“…Increased binding to plasma proteins facilitates drug accumulation in tissues. As a result, non-ionizing parts of the drug increase, and the interaction level of the drug and the lipid structure of the cell membranes also increase (7)(8)(9).…”