Toxicological Assessment of Lamivudine-Artesunate Treatment on Renal Function, Renal Histology and Some Biomarkers in Parasitized and Immunosuppressed Rodents

Abstract

The endemic nature of malaria and the prevalence of the viral infections of HIV and HBV in Africa necessitate concurrent lamivudine and artesunate therapy, and these drugs are amongst first line agents in management of these diseases. This study investigated the safety of lamivudine-artesunate co-administration in a rodent model of Plasmodium berghei infection in cyclophosphamide-induced immunosuppression. Thirty Wistar rats divided into five groups were used for the study with intraperitoneal drug administration for 21 days. Group 1 served as healthy controls while group 2 was disease control (Plasmodium berghei and cylcophosphamide inmmunosuppression). Group 3 and 4 received lamivudine 20mgkg^-1, with group 4 receiving artesunate 10mg kg^-1 in addition. Group 5 received only artesunate. All drugs were administered intraperitoneally and artesunate was from day 15 while groups 2-5 were also diseased. Electrolytes and urea levels did not differ significantly between treated and disease controls. Relative kidney weights were within close range of each other in all groups including the vehicle group. While lymphocytes were significantly lower in the lamivudine group, PCV levels were significantly decreased with artesunate in the disease group. Histological observations however did not show much difference and correlated the electrolytes and urea data from serum analysis. Data from this study suggests that concurrent administration of lamivudine and artesunate in the diseased state of malaria in immunosuppression may not pose severe renal consequences if administration is not intravascular in nature. Further safety studies with longer co administration of lamivudine and artesunate is recommended.

Keywords: Drug safety, drug interaction, antimalarial-antiviral interaction, lamivudine, artesunate