title: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Silesia, Jagiellońska 4, 41-200, Sosnowiec, Poland, abeberok@sum.edu.pl.
authors.forename: Artur
authors.initials: A
authors.lastname: Beberok
authors.forename: Dorota
authors.initials: D
authors.lastname: Wrześniok
authors.forename: Michał
authors.initials: M
authors.lastname: Otręba
authors.forename: Maciej
authors.initials: M
authors.lastname: Miliński
authors.forename: Jakub
authors.initials: J
authors.lastname: Rok
authors.forename: Ewa
authors.initials: E
authors.lastname: Buszman
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D024841:Fluoroquinolones / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000077266:Moxifloxacin; D009643:Norfloxacin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D008543:Melanins; C577219:CAT protein, human; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D009643:Norfloxacin; D000077266:Moxifloxacin