Abstract
Heavy metal toxicity is a common foodborne problem in Egypt, especially in combination. Molybdenum toxicity has been studied as a model of the heavy metal toxicity. Molybdenum could promote toxicity via oxidative-inflammatory mechanisms. Bupropion is a well-known antidepressant that has anti-oxidant mechanisms. It exerts a cytoprotective action against molybdenum induced metal toxicity. The aim of the study is to evaluate the effects of combined bupropion and molybdenum in a toxic animal model. The results showed that the combination of bupropion and high doses of molybdenum was extremely toxic with an evident animal fatality. Bupropion showed a clear anti-oxidant/anti-inflammatory profile detected by the ELISA assay of malondialdehyde (MDA), reduced glutathione, and interleukin -6 (IL-6), and real-time gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and tumor necrosis factor-α (TNF-α). The immunohistochemistry of nuclear factor Kappa Beta (NF-κB) showed that bupropion reduced the inflammatory response induced by the molybdenum neurotoxicity. Despite the improved laboratory profile, the animals were extremely intoxicated with recorded fatalities raising the question about other pathways and mechanisms explaining the drug metal interaction. Furthermore, Bupropion even in normal doses was toxic to the animals. Choroid plexus hyperplasia was reported in the histological examination of the animal brain loaded with bupropion, and choroid plexus papilloma was recorded in the combined drug metal group. More wide-scale studies are needed to verify the safety of the current antidepressant medications for the long-term therapy. It is important to focus on drug metal interaction as a possible cause of neuropathology.