Effect of norfloxacin and moxifloxacin on melanin synthesis and antioxidant enzymes activity in normal human melanocytes

Abstract

Fluoroquinolone antibiotics provide broad-spectrum coverage for a number of infectious diseases, including respiratory as well as urinary tract infections. One of the important adverse effects of these drugs is phototoxicity which introduces a serious limitation to their use. To gain insight the molecular mechanisms underlying the fluoroquinolones-induced phototoxic side effects, the impact of two fluoroquinolone derivatives with different phototoxic potential, norfloxacin and moxifloxacin, on melanogenesis and antioxidant enzymes activity in normal human melanocytes HEMa-LP was determined. Both drugs induced concentration-dependent loss in melanocytes viability. The value of EC50 for these drugs was found to be 0.5 mM. Norfloxacin and moxifloxacin suppressed melanin biosynthesis; antibiotics were shown to inhibit cellular tyrosinase activity and to reduce melanin content in melanocytes. When comparing the both analyzed fluoroquinolones, it was observed that norfloxacin possesses greater inhibitory effect on tyrosinase activity in melanocytes than moxifloxacin. The extent of oxidative stress in cells was assessed by measuring the activity of antioxidant enzymes: SOD, CAT, and GPx. It was observed that norfloxacin caused higher depletion of antioxidant status in melanocytes when compared with moxifloxacin. The obtained results give a new insight into the mechanisms of fluoroquinolones toxicity directed to pigmented tissues. Moreover, the presented differences in modulation of biochemical processes in melanocytes may be an explanation for various phototoxic activities of the analyzed fluoroquinolone derivatives in vivo.

Ciprofloxacin triggers the apoptosis of human triple-negative breast cancer MDA-MB-231 cells via the p53/Bax/Bcl-2 signaling pathway

“…Previous studies have demonstrated that fluoroquinolones, including lomefloxacin (33), norfloxacin and moxifloxacin (34) and sparfloxacin (35) may alter the activity of the cellular antioxidant enzymes superoxide dismutase, catalase and GSH peroxidase. It has therefore been hypothesized that fluoroquinolones may induce cellular oxidative stress by triggering the generation of ROS, particularly the superoxide radical anion and hydrogen peroxide.…”

“…To the best of our knowledge, there have been no previous studies investigating the effect of fluoroquinolones on human TNBC cells. It is hypothesized that fluoroquinolones inhibit bacterial type II topoisomerase (DNA gyrase), however there is also evidence to suggest that they may affect the viability of cells, including cancer cells (12,13,(33)(34)(35). The anticancer activity of topoisomerase inhibitors may potentially occur via the inhibition of mitochondrial DNA synthesis, which subsequently induces mitochondrial injury, disorders in the respiratory chain and depletion of intracellular ATP stores.…”

Kanamycin induces free radicals formation in melanocytes: An important factor for aminoglycosides ototoxicity

“…Tyrosinase activity was estimated by measuring the rate of oxidation of L ‐DOPA to DOPAchrome as previously described . The enzymatic assay was initiated by the addition of 40 μL of L ‐DOPA solution (2 mg/mL) at 37°C.…”

“…Tyrosinase activity was estimated by measuring the rate of oxidation of L-DOPA to DOPAchrome as previously described. 21,22 The enzymatic assay was initiated by the addition of 40 μL of L-DOPA solution (2 mg/mL) at 37°C. The absorbance of DOPAchrome was measured every 10 minutes for at least 1.5 hours at 475 nm using a microplate reader.…”

Development of an ic-ELISA and immunochromatographic strip for detection of sparfloxacin in honey

“…The use of sparfloxacin (SPFX), a third-generation fluoroquinolone antibiotic, is widespread in animals for preventing disease and promoting growth due to its broad-spectrum antibacterial properties (Peng et al, 2016). A deficiency in SPFX leads to phototoxicity, renal-hepatic system damage, and genotoxicity (Beberok et al, 2015;Giacometti, Cirioni, Barchiesi, & Scalise, 2000). Furthermore, long-term exposure to SPFX can result in the emergence of drug-resistant pathogens which increases the risk of death from common infections (Martín-Galiano & de la Campa, 2003;Minnick, Wilson, Smitherman, & Samuels, 2003;Tlili et al, 2016;Weigel, Anderson, & Tenover, 2002).…”