Astemizole-Methylene Blue Combination Therapy Reduces Monotherapy Adverse Effects in Balb/C Mice

Aims: To determine the toxicity of astemizole-methylene blue combination therapy as effective candidates for therapeutic repurposing against malaria.

Study Design: Randomized block study design.

Place and Duration of Study: Department of Tropical and Infectious Diseases, Institute of Primate Research, between July and December, 2019.

Methodology: The Lorke’s technique was used to evaluate the toxicity of the drug combinations in

Balb/c mice (N=25). The mice were monitored for clinical signs at 2-hour intervals. After 48 hours, the mice were euthanized, and their tissues collected, weighed and grossly examined. Biochemistry and hematological tests were performed after blood samples were collected. Analysis of Variance and the t-test were used for statistical analysis; differences were considered significant if P values were less than 0.05 (p˂ 0.05).

Results: The findings revealed that mice treated with methylene blue alone experienced a decrease of appetite, while mice treated with astemizole alone experienced slight tremors, which were not observed in the medication combined groups. When compared to the negative controls, the astemizole-methylene blue 3:1 combination group exhibited reduced heart (p=0.007) and liver (p=0.0001) mean weights. Platelet levels in the astemizole-methylene blue 3:1 group were lower in comparison to the other groups (p=0.005), according to the hematological data collected.

Conclusion: When delivered in ratios with less astamizole, astemizole-methylene blue combination therapy showed better results in terms of safety than monotherapy with either drug alone.