Acute Oral Toxicity of Trichosetin, A Novel Antibiotic Drug Against Methicillin-Resistant Staphylococcus aureus and Bacillus subtilis, in Mice (Mus musculus L.)

Abstract

Trichosetin is a novel antibiotic drug against MRSA and Bacillus subtilis. This study characterizes the toxicity profile of trichosetin. Acute doses of trichosetin were orally administered to male and female ICR-strain Swiss Webster mice. Characterization of toxidromes was executed during a 14-day observation period. Gross examination of the liver, heart, spleen, kidneys, and lungs of mice was performed at the termination of the study. Trichosetin showed a dose-related increase in the magnitude of biological response observed in the toxidromes and body weights of mice. However, no dose-related changes were observed in the gross morphological anatomy and relative weights of the major internal organs of mice. The TD50 for dyspnea was 0.4176 g/kg ± 0.0674 SE. The ED50 for analgesia was 0.3251 g/kg ± 0.0717 SE. The dose-response lines for both dyspnea and analgesia showed a positive, linear, shallow slope. Trichosetin’s therapeutic indices for analgesia and its antibiotic activity are 1.28 and 13,363.2, respectively. The NOAEL of trichosetin was 0.16 g/kg. Trichosetin’s possible target organ system of toxicity is the CNS, which exhibited the most number of toxidromes. Based on the therapeutic index, it was found that trichosetin has a wide margin of safety as an antibiotic drug.