Changes in the Oxidation-Reduction State of Human Dermal Fibroblasts as an Effect of Lomefloxacin Phototoxic Action

Abstract

Phototoxicity induced by antibiotics is a real problem in health care. The discontinuation of antibiotic therapy due to a phototoxic reaction can lead to the development of resistant strains. Fluoroquinolones are widely used antibiotics that exhibit phototoxic activity under UVA radiation. The purpose of the study was to examine the redox status of human dermal fibroblasts exposed to UVA radiation and treated with lomefloxacin, the most phototoxic fluoroquinolone. Lomefloxacin alone was found to have an antiproliferative activity on fibroblasts by affecting the cell cycle. In addition, the drug caused a redox imbalance associated with the decreased expression of catalase and glutathione peroxidase. UVA radiation increased the drug cytotoxicity and oxidative stress induced by lomefloxacin. The decrease in cell viability was accompanied by a high level of reactive oxygen species and extensive changes in the antioxidant levels. The revealed data indicate that the phototoxic action of lomefloxacin results from both increased reactive oxygen species production and an impaired antioxidant defense system. Considering all of the findings, it can be concluded that lomefloxacin-induced phototoxic reactions are caused by an oxidoreductive imbalance in skin cells.

Phototoxic Reactions Inducted by Hydrochlorothiazide and Furosemide in Normal Skin Cells—In Vitro Studies on Melanocytes and Fibroblasts

“…The obtained results allow us to conclude that HCT is the drug causing greater oxidationreduction disorders than furosemide, while fibroblasts are more sensitive cells to oxygen homeostasis disorder than melanocytes. Many drugs with high phototoxic potential, i.e., lomefloxacin or meloxicam, induced disturbances of redox homeostasis in skin cells which resulted in an increase in ROS levels, a decrease in the percentage of cells with high levels of reduced thiols, similar to the tested HCT and FUR [45,48].…”

“…The analysis of the effect of lomefloxacin and UVAR on the fibroblast cell cycle showed similar results relating to the percentage of cells in the G1/G0 and G2/M phases as the HCT and FUR studies. Conversely, a decrease in the percentage of fibroblasts in the S phase was observed [48]. Although cell cycle disruption is one of the symptoms of phototoxicity, the direction of change may depend on the tested drug and used cell line.…”

Study of the impurity profile of photodegradation in lomefloxacin hydrochloride ear drops using liquid chromatography combined with ion trap/time‐of‐flight mass spectrometry

“…According to the literature, it was considered to be associated with photosensitivity reactions. 5,6 And the impurity profile has continued to receive attention from regulatory authorities. Therefore, it is necessary to characterize and control photodegradation impurities in lomefloxacin hydrochloride.…”

“…This product is very unstable to light, easily producing photodegradation impurities. According to the literature, it was considered to be associated with photosensitivity reactions 5,6 . And the impurity profile has continued to receive attention from regulatory authorities.…”