Metronidazole does not show direct antioxidant activity in in vitro global systems

Abstract

Metronidazole has been widely used topically and systemically for more than 50 years but data on its antioxidant properties are still incomplete, unclear and contradictory. Its antioxidant properties are primarily hypothesized based on in vivo results, therefore, studies have been performed to determine whether metronidazole has antioxidant activity in vitro. We used so-called global spectrophotometric and luminometric methods. Fe³⁺/Fe²⁺-reducing ability, hydrogen donor activity, hydroxyl radical scavenging property and lipid peroxidation inhibitory activity were investigated. Under the condition used, metronidazole has negligible iron-reducing ability and hydrogen donor activity. The hydroxyl radical scavenging capacity cannot be demonstrated. It acts as a pro-oxidant in the H₂O₂/^.OH-microperoxidase-luminol system, but it can inhibit the induced lipid peroxidation. According to our results, metronidazole has not shown antioxidant activity in vitro but can affect redox homeostasis by a ROS-independent mechanism due to its non-direct antioxidant properties.

Keywords: Hydrogen donor activity; Lipid peroxidation inhibition; Metronidazole.

Figure 1

Protocol of global measurements of metronidazole antioxidant property.

Figure 2

Hydrogen donor activity of metronidazole as a function of concentration. ∗Significant difference (p < 0.05) compared to the inhibition % at the lowest concentration.

Figure 3

Concentration-dependent hydroxyl radical generation of metronidazole in H₂O₂/□OH microperoxidase-luminol system (RLU: relative light unit). ∗Significant difference (p < 0.05) compared to the background intensity.

Figure 4

Lipid peroxidation inhibition of metronidazole. ∗Significant difference (p < 0.05) compared to the lipid peroxidation value of sunflower oil.