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Phototoxic potential of quinolone antibacterial agents in Balb/c mice
N Wagai1, F Yamaguchi, M Sekiguchi
1Research Institute, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Abstract:
The phototoxic potentials of quinolone antibacterial agents were investigated in Balb/c strain mice. The mice were orally administered nalidixic acid (NA), enoxacin (ENX), ofloxacin (OFLX), ciprofloxacin (CPFX), lomefloxacin (LMFX) and DR-3355 (s-isomer of OFLX), and immediately exposed to ultraviolet-A (UVA) for 4 h (21.6 joules/cm2). The ears were examined for overt damage, as a major phototoxic parameter, 0, 24 and 48 h after irradiation ended. At doses of 200 mg/kg, LMFX, NA and ENX caused marked cutaneous phototoxic reactions on the ears, whereas CPFX, OFLX and DR-3355 caused none. At 800 mg/kg, however, CPFX, OFLX and DR-3355 also caused phototoxic reactions on the ears. These phototoxic changes were characterized grossly by erythema, and histopathologically by edema and infiltration of inflammatory cells, especially neutrophils, into the connective tissue surrounding the cartilage. The 50% erythema-inducing doses of LMFX, ENX, NA, OFLX, DR-3355 and CPFX were calculated at 19, 102, 143, 553, 619 and 741 mg/kg, respectively. Thus, the phototoxic potencies of the quinolones tested were: LMFX greater than ENX, NA greater than OFLX, DR-3355, CPFX.
Insights
Lomefloxacin, nalidixic acid, and enoxacin showed significant phototoxic reactions in mice exposed to UVA light. Other quinolones like ciprofloxacin and ofloxacin exhibited phototoxicity only at higher doses.
Area of Science:
- Pharmacology
- Dermatology
- Toxicology
Background:
- Quinolone antibacterial agents are widely used.
- Some quinolones are known to cause phototoxic reactions.
- Understanding the phototoxic potential is crucial for patient safety.
Purpose of the Study:
- To investigate and compare the phototoxic potentials of various quinolone antibacterial agents.
- To determine the dose-dependent phototoxic effects of these agents in a murine model.
Main Methods:
- Balb/c mice were orally administered different quinolones (nalidixic acid, enoxacin, ofloxacin, ciprofloxacin, lomefloxacin, DR-3355).
- Mice were exposed to ultraviolet-A (UVA) radiation.
- Phototoxic reactions, primarily erythema on the ears, were assessed at 0, 24, and 48 hours post-irradiation.
Main Results:
- Lomefloxacin, nalidixic acid, and enoxacin induced marked phototoxic reactions at 200 mg/kg.
- Ciprofloxacin, ofloxacin, and DR-3355 showed no phototoxicity at 200 mg/kg but did at 800 mg/kg.
- Histopathological examination revealed erythema, edema, and neutrophil infiltration.
Conclusions:
- The phototoxic potencies varied significantly among the tested quinolones.
- Lomefloxacin, enoxacin, and nalidixic acid were found to be more phototoxic than ofloxacin, DR-3355, and ciprofloxacin.