The Effect of Metamizole on Viability and Oxidative Stress in the C6 Rat Glioma Cell Line

Metamizole is a pyrazolone-derived drug with analgesic, antipyretic and spasmolytic activity. The available literature data on metamizole effects on tumor cell lines is limited. Modulation of oxidative stress is considered to be an important mechanism through which different drugs may influence tumor cell survival. Objective of this study was to evaluate the effect of metamizole on viability and oxidative stress levels in the C6 rat glioma cell line. C6 cells were treated with metamizole and N-acetylcysteine (NAC) for 24h and 48h. Cell viability was determined using crystal violet and MTT assays. Viability of C6 cells was also determined after combined treatment with metamizole and NAC. Combined treatment doses were determined based on IC₅₀ values. To assess oxidative stress, levels of malondialdehyde and reduced glutathione were measured in cell culture media. Our results showed that metamizole reduced C6 cell viability in a dose- and time-dependent manner, especially after 48h, with significant reduction of viability, even at lower concentrations. The reduced cell viability and pro-oxidative effects were mainly observed at high metamizole concentrations - 40μg/mL and 80μg/mL. NAC alone, in low concentrations, did not significantly impair cell viability and had slightly improved antioxidant status. In combined treatments, 1mM NAC was partially able to counteract metamizole-induced cell death of C6 cells. Therefore, we can conclude that metamizole reduces viability of the C6 cell line, especially after long-term exposure with significant changes of malondialdehyde and glutathione levels, influencing the C6 cell viability at least partially via oxidative stress.