Metronidazole-induced neurotoxicity: is iron a contributing factor?

Abstract Background Metronidazole-induced neurotoxicity is a rising challenge in the management of susceptible infections. The mechanisms involved in metronidazole-induced neurotoxicity are not fully unraveled. This study was aimed at determining the effect of metronidazole on iron homeostasis in SH-SY-5Y neuroblastoma cells. Methods Confluent SH-SY-5Y neuroblastoma cells were treated with 1, 10, 25, 50, 100, 250 µM concentrations of metronidazole only or in combination with 20 µM iron. DMSO or culture media was used as control. Viability and ferritin assay were conducted on the treated cells. The treatments were for 24 hr, 48 hr and 72 hr respectively. Results In the viability assay, doses of metronidazole reduced viability of SH-SY-5Y neuroblastoma cells in a time and concentration dependent manner. After 24 hr treatment, 250 µM metronidazole reduced (P < 0.001) cell viability while 50 µM, 100 µM and 250 µM metronidazole reduced (p < 0.01, p < 0.001) viability only after 48 and 72 hr compared with control. Doses of metronidazole 50 µM, 100 µM and 250 µM in 20 µM iron reduced viability in a time dependent manner in all the tests periods. Metronidazole also induced a time and concentration dependent increase (P < 0.05) in cellular iron uptake in the 48 and 72 hr treated cells in concentrations above 25 µM metronidazole. Conclusion It is concluded that metronidazole induces a time and concentration dependent iron overload and consequent cell death in SH-SY5Y neuroblastoma cells and this may contribute to the mechanism of metronidazole-induced neurotoxicity.