Acute and subacute (20-d) oral dose toxicity study of modified fluoroquinolone compound 6C in BALB/c mice

摘要

Introduction: Antibiotics are compounds used to treat inflammation; fluoroquinolones are antibiotics used in resistant cases. Objective: The purpose of this study was to investigate acute and subacute toxicity for a new modified flouroquinolone compound (MFC 6C) - a broad spectrum antibiotic which was invented at Faculty of Pharmacy in University of Jordan - using BALB/c mice. Materials and methods: In the pilot study (8 groups; 1 Male:1 Female/group), MFC 6C was administered to these mice at dose levels of 500, 600, 700, 1000, 1200, 1600, 3000 and 5000mg/kg/d. In the subacute study (5 groups; 5 Males:5 Females/group), MFC 6C was administered for two groups at dose levels of 500, 250mg/kg/d for 20d by oral gavage; other groups were control groups. Results: Before the acute study, a pilot study was conducted (on 8 separate days) and no mortality was found even at 5000mg/kg; therefore, LD50 was found to be >5000mg/kg and no further acute effects need to be investigated; so MFC 6C is slightly toxic. The biochemical study revealed that, in subacute toxicity study (20 consecutive days), MFC 6C 500mg/kg caused a decrease in male and female mice blood serum SGOT [p=0.0189 (for males), 0.0309 (for females)] and a decrease in male mice blood serum CPK level (p=0.023). MFC 6C (250mg/kg) caused a significant decrease of male mice blood serum sugar (p=0.04278) and CPK level (p=0.005). The histopathological study revealed that, in subacute toxicity study (20 consecutive days), MFC 6C (500mg/kg) caused; periportal lymphocytic inflammation (male, 60%; female 40%), lymphoid follicle (female, 60%), neutrophilic aggregation and mitotic activity (female, 40%) in the liver. Moreover, it caused interstitial lymphocytic inflammation (male 60%; female 20%) in the kidney. Other changes like follicular hyperplasia (male 40%) were observed in the spleen. It also caused neutrophilic aggregation (male 40%) in the heart. Also, congestion and macrophages were observed. Changes like lymphocytic infiltration (male 20%; female 20%), congestion (male, 20%) and pleural mesothelial hyperplasia (female, 20%) were found in the lungs. MFC 6C (250mg/kg), in subacute study, caused; lobular lymphocytic infiltration (male 100%; female 100%), portal lymphocytic inflammation (male 40%; female 40%), granuloma and extramedullary hematopoeisis (male 20%; female 20%), apoptotic bodies and plasma collection in the liver. On the other hand, it caused; reactive lymphoid hyperplasia (male 20%; female 20%) in the spleen. Fibrinous pericarditis (male 40%; female 40%), pericardial mesothelial hyperplasia and degenerated myofibers (male 20%; female 20%) were observed in the heart. Parenchymal lymphocytic infiltration was observed in the lungs (male 40%; female 40%). While no changes occurred in testis at the dose (250mg/kg). No observed effect level (NOEL) was 125mg/kg/d for 20-d subacute toxicity study. Conclusion: MFC 6C may suppress the function andor morphology of the body organs.