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Chronotoxicity of Streptomycin-Induced Renal Injury in Mice
Hiroki Yoshioka1, Sarah Tominaga1, Yasuro Shinohara1
1College of Pharmacy, Kinjo Gakuin University.
Abstract:
The aim of the present study was to investigate the "chronotoxicity" of streptomycin (SM) in relation to its circadian periodicity. Male ICR mice were injected intraperitoneally with SM (780 mg/kg, one shot) one of six time points throughout the day. Mortality was monitored until 14 d after the injection and clearly differed depending on the timing of the injection (i.e., mice were more sensitive to injection during the dark phase). Moreover, when mice were administered with non-lethal doses of SM (550 mg/kg, every 24 h for 3 d, in the light phase or dark phase), the levels of nephrotoxicity indicators (blood urea nitrogen and renal levels of malondialdehyde and cyclooxygenase-2) were significantly increased by the injection in the dark phase, but not in the light phase. These results suggested that SM showed clear chronotoxicity. Our current data indicated that chronotoxicology may provide valuable information on the importance of injection timings for evaluations of toxicity and undesirable side effects.
Insights
Streptomycin (SM) exhibits chronotoxicity, with higher toxicity and nephrotoxicity observed when administered during the dark phase in mice. Injection timing significantly impacts SM
Area of Science:
- Pharmacology
- Chronobiology
- Toxicology
Background:
- Circadian rhythms influence physiological processes, potentially affecting drug efficacy and toxicity.
- Understanding temporal variations in drug response is crucial for optimizing treatment and minimizing adverse effects.
Purpose of the Study:
- To investigate the "chronotoxicity" of streptomycin (SM) by examining its toxicity and side effects in relation to circadian periodicity.
- To determine if the timing of SM administration influences its lethal and non-lethal toxic effects.
Main Methods:
- Male ICR mice were administered a single high dose of streptomycin (780 mg/kg) at six different time points throughout a 24-hour cycle.
- Mortality was monitored for 14 days post-injection.
- Mice received non-lethal doses (550 mg/kg daily for 3 days) during either the light or dark phase, and indicators of nephrotoxicity (blood urea nitrogen, renal malondialdehyde, cyclooxygenase-2) were measured.
Main Results:
- Mortality rates significantly differed based on the time of streptomycin injection, with higher sensitivity observed during the dark phase.
- Non-lethal doses of streptomycin administered during the dark phase led to significant increases in nephrotoxicity indicators compared to administration during the light phase.
- Streptomycin demonstrated clear chronotoxicity, with toxicity being time-dependent.
Conclusions:
- The timing of streptomycin administration is a critical factor influencing its toxicity and potential for adverse side effects.
- Chronotoxicology, the study of time-dependent toxicity, offers valuable insights for evaluating drug safety and optimizing administration schedules.
- These findings highlight the importance of considering circadian rhythms in drug development and clinical practice.
