Evaluation the Cytotoxicity of Moxifloxacin in vivo and its Effect on the Functions and Tissues of the Liver and Kidney of Albino Male Mice

Background: Moxifloxacin (MXF) is a broad spectrum fluoroquinolone antibiotic effective for respiratory and urinary tract infections. There are concerns that it may be cytotoxic and/or have organ-selective effects. Methods: In vitro, WRL 68 (human liver) and HDFn (neonatal dermal fibroblast) cells were grown under standard condition at 37°C in Biotechnology Research Center/Al Nahrain University laboratory as control culture dish to apply MXF with concentrations of 12.5-400 µg/mL for 24 h. In vivo A total of 18 albino male mice were assigned into three groups (n=6 each) as follows: The control (given distilled water), MXF 500 and MXF 750 mg/kg treated intraperitoneally for a period of 15 days. Cell viability, micronucleus formation, hepatorenal function tests and histopathological studies were performed. Result: MXF was cytotoxic in vitro at dose-dependent manner. Viability in WRL 68 cells was reduced from 95.3±0.6% at 12.5 µg/mL to 60.1±0.6% at 400 µg/mL or cytotoxicity of the range of 5.3-39.3%. HDFn cells were the most resistant (viability, 98.0±0.4% to 81.8±0.8%; cytotoxicity, 2.1-19.6%). In vivo, MN frequency in bone marrow were also significantly elevated at 750 mg/kg MXF (0.035±0.005 Mn/cell) vs controls (0.019±0.002 Mn/cell), while with 500 mg/kg only a small not significant increase was observed (0.021±0.003 Mn/cell). Liver enzymes (AST, ALT and ALP) were dose-dependent being 70.6±2.4, 67.1±2.42 and 200.1±21.5 U/L at 750 mg/kg when compared to control stress animal (45.5±1.37, 40.3±3.12, 79.4±8.7 U/L). There were increased levels of urea (58.7±5.4 mg/dL and 43.1±1.4, respectively) with no significantly differences in creatinine content. These biochemical results were consistent with the histology findings: moderate hepatitis and focal necrosis of the liver in mice given 750 mg/kg/day, no remarkable change in kidney at 500 mg/kg/day and almost normal architecture at a dose also of 750 mg/kg/day.