Induced and Photoinduced DNA Damage by Quinolones: Ciprofloxacin, Ofloxacin and Nalidixic Acid Determined by Comet Assay¶

Abstract

Quinolones are degraded by light with loss of their antimicrobial activity, generating active species or radicals. Evidence exists that some fluoroquinolones (lomefloxacin, fleroxacin and enoxacin) induce damage to the cellular membrane and DNA cleavage by photosensitization. In this study, the genotoxic potential of the quinolones ofloxacin, nalidixic acid and ciprofloxacin (three antimicrobials frequently used in therapy) was evaluated upon irradiation with UV light by using the comet assay on cells of the Jurkat line. The results demonstrate that there are significant differences between the control groups (positive control with 50 microM H2O2, negative controls without drug and with and without irradiation) and the groups of irradiated quinolones (ofloxacin 2.76 x 10(-5) M, nalidixic acid 2.15 x 10(-4) M and ciprofloxacin 2.01 x 10(-5) M), indicating that, at the dose of irradiation employed (necessary to produce 50% photodegradation), the photodecomposition of the quinolones enhanced DNA damage. The unirradiated drugs also exhibited genotoxicity significantly different from that of the negative control.

Photoinduced Superoxide Radical Anion and Singlet Oxygen Generation in the Presence of Novel Selenadiazoloquinolones (An EPR Study)

“…superoxide radical anion, hydroxyl radical, singlet oxygen) has been confirmed upon irradiation of lomefloxacin, enoxacin, ofloxacin and ciprofloxacin (16,20,21), but no correlation has been found between singlet oxygen generation and phototoxic impact (21). The potential photoreactivity channels of fluoroquinolone drugs have been discussed in the literature and it has been shown that not only the formation of singlet oxygen as a primary reactive species causing DNA‐photosensitized oxidation (20–22), but also triplet energy transfer appears to be mostly responsible for the phototoxic effects of fluoroquinolones (23).…”

Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

“…Photoinduced Comet formation has been revealed with ENO (62), RUF (70,71), FLE (93), NOR (62,93), BAY (93,106), SPA (112,121), LOM (62,93,94,105,106,122,123), CLI (122), CIP (93,122,124) and OFL (62,112). This latter was shown inefficient by other authors (124). Repair enzymes in Comet assay have revealed purine bases oxidations through formation of Fpg‐sensitive sites on tumoral cells photosensitized by ENO, LOM, OFL and NOR (62).…”

Testicular Morphological Changes Produced by Fluoroquinolones in Adult Male Albino Rats

“…Studies using rats treated with therapeutic doses of fluoroquinolones confirmed the observation in humans regarding the adverse effect of fluoroquinolones on spermatogenesis. 23 Changes observed on light microscope include expansion of interstitial and intertubular space with vacuolization, degeneration and necrosis of interstitial (leydig) cells following which an exudation into the interstitium was developed and congestion in veins increased in all experimental groups as compared to control groups showing P value < 0.05 that is significant. Multiple comparison among study groups showed that Ciprofloxacin produced less morphological changes (Fig.…”