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

Abstract

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 5000 mg/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, 250 mg/kg/d for 20 d 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 5000 mg/kg; therefore, LD₅₀ was found to be >5000 mg/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 500 mg/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 (250 mg/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 (500 mg/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 (250 mg/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 (250 mg/kg). No observed effect level (NOEL) was 125 mg/kg/d for 20-d subacute toxicity study. Conclusion: MFC 6C may suppress the function and\or morphology of the body organs.

• Biochemistry
• BALB/c mice
• fluoroquinolones
• histopathology
• MFC 6C

Acknowledgements

The authors thank Dr Ahmad Al Dissi, Dr Abdelkader Battah, Miss Amal Majdalawi and Miss Khairat Battah for their assistance. The authors also express their gratitude toward Dr Fatmeh Obaidat and Dr Ala'a Ali Alsubeihi.

Declaration of interest

The authors have no conflicts of interest to declare.