## 1 Introduction  
Fluoroquinolones are a group of synthetic, broad-spectrum antibiotics patented in the late nineties, including norfloxacin (1978), pefloxacin (1979), enoxacin (1980), ciprofloxacin (1981), fleroxacin (1981) and ofloxacin (1982) [1], and are still used today. In Figure 1, the general structure of fluoroquinolones, with an accepted numbering scheme for positions on the molecule, is shown. In the 1980s, there was a big revolution when enoxacin, an analog of nalidixic acid, was derived with a significantly increased spectrum of antibacterial activity [2]. Ciprofloxacin, the most successful and widely accepted fluoroquinolone, was marketed in 1986; since then, fluoroquinolones have become recognized as promising agents for controlling a wide range of infections, including gastrointestinal, urinary, respiratory, skin and ocular infections [2, 3, 4, 5]. This class of compounds has enhanced pharmacokinetic properties, with extensive and potent activities against parasites, bacteria and mycobacteria, including resistant strains that outperform the bactericidal drugs existing previously [5,6]. However, in an attempt to retain their effectiveness, the present guidelines mostly recommend this class as second-line agents to prescribe when narrow-spectrum antibiotics have failed [7]. Despite their excellent antibacterial properties, phototoxicity is a rare, but characteristic, side effect of fluoroquinolone antibiotic use [9], which is believed to be associated with UVA-induced drug degradation, resulting in the formation of reactive oxygen species (ROS), causing oxidative damage to cell components, including lipids, proteins and nucleic acids [10, 11, 12, 13]. Fluoroquinolone-induced skin phototoxicity may appear in vivo, with different degrees of severity, as exaggerated sunburn-like lesions, blisters, scaling, edema, erythema, eczematosus and bullous eruptions in areas of the skin exposed to sunlight or artificial UVA radiation [9,14, 15, 16, 17]. Melanocytes, a heterogeneous group of cells, have the ability to produce a pigmented protein called melanin, primarily responsible for skin, hair and eye color. Tyrosine, being a limiting enzyme for melanogenesis, affects melanin biosynthesis significantly. It catalyzes the hydroxylation of L-tyrosine to 3,4-dihydroxyphenylalanine (L-DOPA) and L-DOPA to dopaquinones [18], resulting in the accumulation of melanin pigments. There are two types of epidermal melanin, eumelanin and pheomelanin, known for their photoprotective and photo-toxic properties [19,20]. Melanin bears antioxidant properties, and a strong affinity for drugs and other chemical substances. Therefore, it efficiently filters toxic substances and protects body tissues from oxidative and chemical stress. The affinity of melanin for drugs restricts their access to cell receptors, and then releases them from the complexes in non-toxic concentrations, protecting the tissues from their undesirable side effects. However, the affinity of melanin for drugs may result in them becoming over accumulated in cells. In particular, their long-term intake and the slow release of their metabolites may elevate the level of noxious substances stored on melanin, causing degeneration in the melanin-containing cells (present in the eye and skin) and surrounding tissues [21, 22, 23]. It was suggested that the toxic reactions of fluoroquinolones [24, 25, 26], tetracyclines [27, 28] and phenothiazines [29], directed to pigmented tissues, may be related to the accumulation of drugs in melanin biopolymers. The effect of fluoroquinolone antibiotics, such as ciprofloxacin [26], lomefloxacin [30], sparfloxacin [26], norfloxacin and moxifloxacin [31, 32], on the antioxidant status and melanin synthesis in normal human melanocytes (HEMa-LP) is extensively studied, with all suggesting melanin-associated drug-induced toxicity.