Extensive use of methyl tert-butyl ether (MTBE) has raised significant threats to the environment through pollution of environmental resources including ground waters. This compound could accumulate in the blood stream through inhalation of contaminated air since MTBE has a high affinity for blood proteins. The interaction of blood proteins such as human hemoglobin (Hb) with MTBE results in conformational and likely functional changes. The main mechanism for harmful effects of MTBE on Hb is through production of reactive oxygen species (ROS). In this regard, the present work was proposed to study the possible antioxidant potential of two dietary antioxidant agents, curcumin and caffeine, on the reduction of MTBE damage on Hb. Different spectroscopic methods including fluorescence, UV-Vis, circular dichroism, chemiluminescence, and molecular docking were used to study the interactions of curcumin and caffeine with Hb in the presence of MTBE. Our results showed caffeine could decrease the aggregation and ROS effects of MTBE on Hb. However, in the presence of curcumin the MTBE mediated aggregation of Hb was enhanced. These opposing effects of curcumin and caffeine as antioxidants were mainly contributed to the high iron chelating activity of curcumin. Thus, the complex formation between curcumin and heme further enhanced ROS production capability of MTBE.
