Photohaptenic Properties of Fluoroquinolones

Abstract

Although quinolone antibacterial agents have both phototoxicity and photoallergenicity, the latter's potency has been poorly investigated compared with the former's. Some of the photoallergic chemicals serve as photohaptens, which lead to T-cell-mediated immune reactions after photobinding to protein by UVA radiation. We examined the photohaptenic potential of fluoroquinolones, including lomefloxacin (LFLX), ciplofloxacin, norfloxacin, ofloxacin, levofloxacin, fleroxacin, enoxacin and sparfloxacin (SPFX). The absorption spectra of the quinolones were altered by UVA irradiation, with an exception of SPFX that seems to be photostable toward UVA. Bovine serum albumin and murine epidermal cells were coupled with these fluoroquinolones other than SPFX by exposure to UVA. Subcutaneous inoculation of fluoroquinolone-photomodified epidermal cells induced and elicited a delayed-type hypersensitivity reaction in mice. However, epidermal cells incubated with LFLX without UVA exposure also induced and elicited a significant hypersensitivity reaction to a lesser degree than LFLX-photomodified epidermal cells. Furthermore, there was cross-reactivity between LFLX-photomodified epidermal cells and simply LFLX-incubated cells. This suggests that cells can be weakly modified with LFLX even in the dark and that UVA irradiation promotes this modification. Our study demonstrated that fluoroquinolones have photohaptenic properties to which their photoallergenicity is probably ascribed.

Photoinduced modifications by fluoroquinolone drugs in bovine serum albumin (BSA) and ribonuclease A (RNAse) as model proteins

“…An interesting behaviour was exhibited by LMX for which we observed an increase of the fluorescence. This effect could be due to the formation of a photoadduct between the protein and the drug as postulated by Tokura et al 21 . Figure 9.…”

“…In this context we have demonstrated that the fluoroquinolones are able to photodamage some aminoacids in particular Tyr and His. An important aspect to clarify with further experiments is the photohaptenic property of fluoroquinolones by which is originated their photoallergenicity 21 . The experiments carried out with LMX suggest the formation of a covalent adduct between the proteins and the drug.…”

A novel in vitro method for the detection and characterization of photosensitizers

“…SPFX, an extreme phototoxic chemical with weak photoallergenic properties [20] induced a significant DCD86 increase (Fig. 4C) under irradiation conditions compared to non-irradiated cells.…”

Stimulation of Langerhans cells with ketoprofen plus UVA in murine photocontact dermatitis to ketoprofen

“…In general, photoreactions by photosensitive chemicals are divided into the phototoxic and photoallergic types. While phototoxicity is mediated by active oxygen, especially singlet oxygen [8,9], photoallergy occurs as a consequence of a specific immune reaction mediated by antigenspecific, sensitized T cells [10][11][12][13][14]. KP has both phototoxic and photoallergic potentials, but many clinical observations have indicated that photosensitivity to KP is a photoallergic reaction [1][2][3][4][5][6][7].…”

“…The two theories, named photohapten and prohapten models, have been put forward to explain the formation of photoallergen [11,14]. According to the photohapten theory, photosensitizing chemicals and protein need to coexist upon exposure to UVA in a noncovalent manner, and UVA turns it covalent [11,14].…”