article · Chronobiology in Medicine
An animal study examined whether the timing of drug administration across different times of day and seasons affects liver damage caused by gentamicin and artesunate. Male Wistar rats were treated once daily for seven days during both the rainy and dry seasons, receiving either saline, gentamicin, artesunate, or a combination of both drugs at midday or midnight. The researchers measured liver enzymes, antioxidant markers, and tissue damage. The findings showed that seasonal timing and the time of day interacted to alter drug toxicity. Liver damage was most severe when treatments were given at midnight during the dry season, leading to the highest liver enzyme elevations, greater reductions in antioxidant levels, and more marked tissue necrosis. Additionally, artesunate reduced certain gentamicin-related harms during the rainy season, but this protective effect disappeared during the dry season.
Drug toxicity can vary depending on when medications are taken. Demonstrating that environmental seasons and daily dosing schedules change how drugs damage the liver suggests that treatment timings could be adjusted to reduce harmful side effects. This finding highlights the value of chronotherapy, especially in regions experiencing strong seasonal shifts, to help ensure that medicines are administered safely.
This work represents early-stage preclinical research that could inform chronotherapeutic dosing protocols and clinical trial designs for pharmaceuticals. The immediate users would be clinical researchers and healthcare providers evaluating therapeutic safety for antimalarial and antibiotic combinations. As the findings are based entirely on rat models, practical application in human medicine remains distant and will require translation and clinical validation in human trials.
AI-generated from the published abstract. Always read the original work before citing.
Objective: This study aims to determine whether time-of-day (12:00 h vs. 00:00 h) and season (rainy vs. dry) modify liver injury induced by gentamicin and artesunate in male Wistar rats. Methods: A total of 128 male Wistar rats were randomized to 16 groups (n=7–8/group) and treated once daily intraperitoneal for 7 days with normal saline, gentamicin (120 mg/kg), artesunate (100 mg/kg), or the combination during the rainy (August 2023) and dry (February 2024) seasons. Primary outcomes were serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP); secondary outcomes included superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and liver histology. Normality and homogeneity of variance were assessed using the Shapiro–Wilk and Levene tests. Two-way analysis of variance (ANOVA; season×dosing time) with Bonferroni correction was used to evaluate effect sizes (partial η2) and 95% confidence intervals (CIs). Results: Two-way ANOVA revealed significant season×dosing-time interactions for ALT, AST, and ALP (all p<0.01; partial η2≈0.10–0.25). Overall, dry-season exposure produced larger enzyme elevations and greater reductions in antioxidant activities than rainy-season exposure. Nighttime dosing (00:00 h) in the dry season produced the largest ALT increases compared with rainy-season daytime saline (p<0.001). Histology corroborated biochemical findings, showing more pronounced necrosis and inflammatory infiltration with dry-season night dosing. Artesunate attenuated some gentamicin-induced changes in the rainy season but not in the dry season. Conclusion: Season and dosing time jointly modulate artesunate–gentamicin hepatotoxicity in rats; dry-season nighttime dosing markedly increases injury. These results support chronotherapeutic consideration in settings where seasonal environmental stressors vary.
This page summarises published work. The authoritative version sits with the publisher.
DOI: 10.33069/cim.2025.0065
Is something wrong with this record? Report it or request removal.
Discussion
Have you built on this work, tried to replicate it, or seen it applied in practice? Share what you know. Verified researchers and MARATTO™ domain experts can open a discussion, and any member can reply. Contributions are reviewed before they appear.
No discussion yet. Open the first thread.
New to MARATTO™? Create a free account.
