Oral toxicity of pefloxacin, norfloxacin, ofloxacin and ciprofloxacin: comparison of biomechanical and histopathological effects on Achilles tendon in rats

Abstract

-Four fluoroquinolones (pefloxacin, norfloxacin, ofloxacin and ciprofloxacin) were compared according to their biomechanical and histopathological effects on rat Achilles tendon. Wistar rats were divided into one untreated control and four treatment groups in parallel. Pefloxacin mesylate dihydrate (40 mg/kg), norfloxacin (40 mg/kg), ofloxacin (20 mg/kg) and ciprofloxacin (50 mg/kg) were administered by gavage twice daily for three consecutive weeks. 6 weeks after treatment, the test animals were euthanised and Achilles tendon specimens were collected. A computer monitored tensile testing machine was utilised for biomechanical testing. The mean elastic modulus of the control group was significantly higher than that of the norfloxacin and pefloxacin groups (p < 0.05 and p < 0.01, respectively). The mean yield force (YF) of the control group was significantly higher than those of ciprofloxacin, norfloxacin and pefloxacin groups (p < 0.001, p < 0.05 and p < 0.01, respectively). The mean ultimate tensile force (UTF) of the control group was significantly higher than of the ciprofloxacin, norfloxacin, and pefloxacin groups (p < 0.001, p < 0.05 and p < 0.01, respectively). Hyaline degeneration and fibre disarrangement were observed in the tendons of the ciprofloxacin, pefloxacin, and ofloxacin treated-groups, whereas myxomatous degeneration was observed only in the ciprofloxacin and pefloxacin groups. In conclusion, these findings in our rat model reveal significant deterioration of biomechanical parameters following fluoroquinolone exposure, and indicate significantly higher biomechanical toxicity for ciprofloxacin and pefloxacin.

Ciprofloxacin is an inhibitor of the Mcm2-7 replicative helicase

“…Such inhibitors also have potential utility for biochemical studies, especially using systems (e.g., Xenopus egg extracts [39]) that have highly tractable biochemical advantages but are poorly amenable to genetic manipulation. Secondly, the discovery that fluoroquinolones can inhibit the eukaryotic helicase may explain some of the cytotoxic effects observed with ciprofloxacin and other fluoroquinolones [40]. Our finding that the mcm4chaos3 allele confers resistance to ciprofloxacin supports our hypothesis that the Mcm2-7 complex is a ciprofloxacin target in cells and suggests that it could also be contributing to the deleterious side effects seen with this class of compounds.…”

Experimental and theoretical studies on the molecular properties of ciprofloxacin, norfloxacin, pefloxacin, sparfloxacin, and gatifloxacin in determining bioavailability

“…The range of antimicrobial activity exhibited by newer fluoroquinolones includes most Gram-negative bacteria ( Salmonella , Shigella ), Gram-positive bacteria ( Streptococci and Staphylococci ) and atypical strains such as Chlamydia , Mycoplasma , Legionella , Pseudomonas aeruginosa , and Mycobacterium tuberculosis . Drugs of the second, third, and fourth generations contain an additional fluorine atom at position 6 of the quinolone core, which affects the pharmacokinetic profile of fluoroquinolones in polar environments and improves their bioavailability and antibacterial activity [1–3]. …”

Ciprofloxacin Induced Chondrotoxicity and Tendinopathy

“…Ciprofloxacin at a dose level of 50 mg kg −1 administered to rats for 3 weeks revealed significant deterioration of Biochemical parameters, hyaline degeneration and fibre disarrangement in the tendon of rats (Olcay et al, 2011).…”