Evaluation of Ciprofloxacin Effect on the Antimalarial Activity of Some Antimalarial Drugs in Plasmodium Berghei Infected Mice

Abstract

Background: Previous animal studies have shown that ciprofloxacin has effect on the antimalarial activity of some antimalarials. Presently in Nigeria, combination of ciprofloxacin and ACTs are commonly prescribed in the treatment of malaria and enteric fever co-infection. Objectives: To evaluate the effect of ciprofloxacin on the antimalarial activity of Artesunate, Artemether-lumefantrine and Artesunate-amodiaquine using mice model. Methods: One hundred and twenty mice infected with chloroquine sensitive Plasmodium berghei NK65 strain were used for this study. The study was carried out in three phases. Phase 1 consisted of AS, AL, ASAQ and CIP treatment groups, the Artesunate (AS) treatment group consisted of three treatment subgroups of four mice per group treated with 3, 6 and 12 mg/kg doses respectively; Artemether-lumefantrine (AL) treatment group consisted of three treatment subgroups of four mice per group treated with 16, 32 and 64 mg/kg doses respectively; Artemether-amodiaquine (ASAQ) treatment group consisted of three treatment subgroups of four mice per group 11, 22 and 44 mg/kg doses respectively, and Ciprofloxacin (CIP1&2) subgroups treated with 7 and 14 mg/kg doses respectively. Phase II consisted of groups of mice treated with 7 mg/kg ciprofloxacin (CIP1) combined with different doses of Artesunate, Artemether-lumefantrine, Artesunate-amodiaquine as used in phase 1 respectively. Phase III consisted of groups of mice treated with 14 mg/kg ciprofloxacin (CIP2) combined with different doses of Artesunate, Artemether-lumefantrine, Artesunate-amodiaquine respectively as in phase I. The dosing of these drugs was based on body weight and administered orally as daily single dose. Thin blood films were used to assess parasitaemia level daily after administration of drugs for 72 hours. The effect of the drugs on the activities of serum Alanine transaminases (ALT) and Aspartate transaminases (AST) were also evaluated. Statistical analysis was done using Student-test and ANOVA. Results: Antimalaria activity of Artesunate was enhanced by ciprofloxacin (7mg/kg) through increased percentage reduction of parasitemia level by Artesunate. The effect of ciprofloxacin 14mg/kg on the three doses of Artesunate was found to be statistically significantly different from that of the same doses of Artesunate at 48 and 72 hr. As the dose of AL combined with CIP2 increased, the percentage maximum reduction decreased. Only the effect of ciprofloxacin on the antimalarial activity of AA 22mg/kg at 72hrs showed a significant difference from the AA at the same doses. Ciprofloxacin significantly decreased ALT and AST activities. Artesunate combined with CIP1 produced a statistically significant decrease in ALT when compared to the control group. All the groups treated with AL showed no statistically significant difference in the ALT and AST activities; apart from AL: CIP2 (64:7mg/kg) which showed significantly increased AST activities. All the groups treated with ASAQ in combination with ciprofloxacin showed a statistically significant decrease in the AST activities apart from ASAQ: CIP2 (44:14mg/kg). Only the groups treated with ASAQ: CIP2 produced a significant decrease in the serum ALT activities. Conclusion: Ciprofloxacin enhanced the antimalarial effects of Artesunate, Artemether-lumefantrine and Artesunate-amodiaquine against the chloroquine sensitive P.berghei in albino mice. This may be beneficial in the management of plasmodium falciparum infection or co-infection with salmonellosis.