Antiplasmodial Activity of Artemether-Lumefantrine-Tinidazole on Plasmodium Berghei Infected Mice

Abstract

Introducion: The impact of malaria scourge has been characterized by daunting challenges including antimalarial drug resistance. This necessitates the search for newer antimalaria drugs using approaches including drug repurposing. This study assessed whether Tinidazole (T) can be repurposed as antimalaria in combination with artemether/lumefantrine (A/L) in Plasmodium berghei infected mice. Materials and Methods: Plasmodium berghei infected mice were grouped and orally treated with A/L (2.3/13.7mg/kg), T (28.6 mg/kg), and A/L/T daily in curative, suppressive and prophylactic studies. The negative control (NC) and positive control (MC) were orally treated with 0.9% normal saline (0.2mL) and chloroquine (CQ) (10mg/kg) daily for 4 days, respectively. After drug administration, blood samples were collected and evaluated for parasitemia level, lipid and hematological parameters. Results: Significant decreases in parasitemia levels in the curative, suppressive and prophylactic groups were observed in mice treated with T (28.6 mg/kg) (p<0.05), A/L (2.3/13.7 mg/kg) (p<0.01) and A/L/T (p<0.001) when compared to negative control. Mean survival times were significantly increased at T (28.6 mg/kg) (p<0.05), A/L (2.3/13.7mg/kg) (p<0.01) and A/L/T (p<0.001) when compared to negative control. Red blood cells, hemoglobin, packed cell volume, high density lipoprotein, cholesterol levels were significantly (p<0.001) increased whereas white blood cells, total cholesterol, triglyceride and low density lipoprotein cholesterol levels were significantly decreased at T (28.6 mg/kg) (p<0.05), A/L (2.3/13.7mg/kg) (p<0.01) and A/L/T (p<0.001) when compared to negative control. The antiplasmodial effect of A/L/T differ significantly (p<0.05) when compared to positive control. Conclusion: This study recommends the repurposing of tinidazole in combination with artemether/lumefantrine for malaria treatment and further studies in humans.

Safety Assessment of Artemether/Lumefantrine/ Tinidazole on the Kidneys of Healthy and Diseased Mice

“…Previous study has shown the antiplasmodial activity of A/L/T in a mouse model infected with P. bergei [14]. Thus study further assessed the safety of A/L/T on the kidneys of healthy and P. bergei infected mice.…”

“…Open label human study showed that T monotherapy followed by weekly doses cleared blood stage infection with no recurrences of P. vivax [13]. In previous studies, we showed promising antimalarial activity of T in combination with A/L characterized by decreased paracetamia, prolonged survival time and decreased anemia in a mouse model infected with P. berghei [14]. Inview of the potential of animalarial drug combinations to cause nephroroxicity, this study assessed the safety of artemether/lumefantrine/ tinidazole (A/L/T) on the kidneys of healthy and diseased mice.…”

“…Artemether/lumefantrine (A/L) (IPAC Laboratory, India) and Tinidazole (T) (Norvatis) were used. The doses of T (28.6 mg/kg), A/L (2.3/13.7mg/kg) and A/L/T used were based on previous antiplasmodial studies [14].…”