Possible Reasons for Differences in Phototoxic Potential of 5 Quinolone Antibacterial Agents: Generation of Toxic Oxygen

Abstract

The reason for the differences in phototoxic potential between the 5 quinolone antibacterial agents lomefloxacin, enoxacin, ciprofloxacin, ofloxacin and DR-3355 (the s-isomer of ofloxacin) in mice was investigated. Superoxide anion, hydrogen peroxide (H2O2), and bleaching of p-nitrosodimethylaniline (B-NDMA) were detected in quinolone solutions during irradiation with ultraviolet-A (UVA). Apparent levels of H2O2 and the B-NDMA per mole of quinolone paralled the phototoxic potentials in the mice. The N-NDMA induced by quinolones and UVA was inhibited partially by treatment with D-mannitol and dimethylsulfoxide, and also with diethylenetriamine-pentaaceticacid (DTPA), suggesting that Haber-Weiss and Fenton reactions occurred. UVA concentration-dependently increased the level of the B-NMDA in H2O2 solution and the swelling in the ear pretreated by intra-auricular injection of H2O2. Both augmentations were inhibited by DTPA or DMSO. The swelling induced by the 5 quinolones and UVA was completely inhibited by pretreatment with dimethylsulfoxide. Oxygen consumption was detectable during the photodegradation, and increased with time. These results showed that the phototoxic potentials of the 5 quinolones were probably related to the amounts of toxic oxygens generated in the target cells during irradiation.

Ciprofloxacin-Induced Antibacterial Activity is Reversed by Vitamin E and Vitamin C

“…Furthermore, a-tocopherol acetate supplementation reduced enrofloxacin residues in turkey meat, which indicate a possible interaction between both molecules that reduces the amount of enrofloxacin in tissues [4,25]. Studies on phototoxic actions of fluoroquinolones revealed that these toxic effects are related to induction of reactive oxygen species [12,23,[27][28][29][30].…”

Efficacy and safety of levofloxacin in the context of other contemporary fluoroquinolones: a review

“…55,56 Phototoxicity Phototoxicity is a potential risk with all contemporary fluoroquinolones, 55 notably those with multiple fluorine side-chain substitution (fleroxacin, sparfloxacin) and those with a chlorine substituent at the 8-position (clinafloxacin, Bay y 3118). 61 In contrast, levofloxacin (1,8 cyclic) and the 8-methoxyquinolones pose minimal risk, [62][63][64][65] probably related to their differentially lesser ability to generate free oxygen radicals in the skin. 64 For these latter agents, phototoxicity, which amounts to no more than mild sunburn, occurs in Ͻ0.05% of patients.…”

“…61 In contrast, levofloxacin (1,8 cyclic) and the 8-methoxyquinolones pose minimal risk, [62][63][64][65] probably related to their differentially lesser ability to generate free oxygen radicals in the skin. 64 For these latter agents, phototoxicity, which amounts to no more than mild sunburn, occurs in Ͻ0.05% of patients. 55,56 QT Interval Prolongation and Ventricular Arrhythmia Prolongation of the QTc by fluoroquinolones and their potential for precipitation of ventricular arrhythmia is a concern.…”

Kozmetik Ürünlerin Fototoksik Etkileri: Mekanizması ve Alternatif Test Metotları

“…UVA ışınıyla oluşturulmuş irritasyon indeksi -ışınlama olmayan irritasyon indeksi (39) 0.6 indeks değeri üzerindeki değerler potansiyel fototoksisiteyi gösterir.…”