Drug Discovery in Preclinical Research (Track)


Kamaljeet Kaur, Arpit Saxena, Suvarthi Das, Yasmine Elraheb, Charles J. Bennett and Raja Fayad

Applied Physiology Division, University of South Carolina, Columbia, SC, USA


Background: The quinolone antibiotic drug Ciprofloxacin treats conditions such as gastroenteritis, respiratory tract infections, urinary tract infections, and prostatitis. However, the usage of the drug is associated with psychopathological symptoms as well as  sensory and motor abnormalities, which usually manifest as tingling and prickling sensations, numbness in the extremities, muscle weakness, tremors, fasciculations and spasms.

Purpose: The purpose of this study is to demonstrate the dosage-dependent role of Ciprofloxacin in inducing peripheral and central nervous system abnormalities in mouse.

Methods: Ciprofloxacin dosages of 10, 20, 30, 40 and 50 mg/kg body weight were administered to C57BL/6 wild type (WT) mice (7-9 weeks old) divided into five groups based on the dosage (n=10), everyday for a period of 10 days via oral gavage. Control mice (n=10) were administered deionized water. The behavioral responses of the mice were observed by grip strength to quantify muscular strength and nerve damage (kgf/kilogram force), and by rotarod to measure motor coordination and balance (total number of rotations) performed every alternate day. The elevated plus maze test to measure anxiety levels in mouse, and the open field test to measure locomotor activity and hyperactivity were also performed twice (day 8 and 13) during the experiment. The mice were sacrificed on day 14th and brain, liver, kidney, quadriceps muscles and blood were obtained. The results were analyzed using One-way and Two-way repeated measure ANOVA.

Results: The treatment group showed a significant decrease in their grip strengths and decreased latencies to fall on the rotarod experiments. Greater anxiety and hyperactive behavior on elevated plus maze and open field were also observed. The changes in the behavioral responses were more pronounced in the mice treated with higher dosages of the drug as compared to lower dosages. Molecular studies including TUNEL assay and immunohistochemistry were performed to explore changes at the molecular level.

Conclusion: Ciprofloxacin may participate in inducing peripheral as well as central nervous system abnormalities in mice, in a dosage-dependent manner that might affect organ systems and can be traced down to cellular and molecular levels.