Molecular mechanism on two fluoroquinolones inducing oxidative stress: evidence from copper/zinc superoxide dismutase

Abstract

Fluoroquinolones (FQs) are very important agents in human health as antibiotics. Regardless of their potential side effects, displayed by all medicines, their value to promote human health cannot be denied. In this paper, we determined the oxidative stress-induced effects of two FQs, ciprofloxacin (CPFX) and enrofloxacin (ENFX), via the essential antioxidant enzyme copper/zinc superoxide dismutase (Cu/Zn-SOD) at its macromolecular and functional level. Cellular study indicated that both FQs elevated vulnerability towards oxidative stress, and CPFX exhibited more of an oxidative threat than ENFX. The analysis using the spectroscopic and computational methods confirmed that both FQs could bind into the interface of two subdomains and alter the microenvironmental and structure of the enzyme. Furthermore, the inhibition of Cu/Zn-SOD activity from the molecular tests was consistent with that in the cellular study. This work provides direct evidence that the increased risk of cellular oxidative stress by two FQs was closely related to the conformational and functional changes of the Cu/Zn-SOD molecule.