Assessment of hepatotoxicity effects of long term administration of SynriamTM in rats

Abstract

Synriam^TM antimalarial drug (SAD), a combination of arterolane malate (150 mg) (a short-acting drug that is effective against all parasite blood stages) and piperaquine phosphate (750 mg) (a slow, long-acting drug that kills residual parasites), has been proven to be safe and effective for malaria treatment in human. However, dearth data is available on its safety in animals. This study investigated the toxicity of SAD on selected liver indices in rats. Thirty-five adult Wistar rats were randomized into five groups (n=7). Group A-Control, Group B-E SAD-treated with 4.0, 8.0, 16.0 and 32.0 mg/kg body weight (bwt.) SAD, respectively, for 28 days. The rats were sacrificed 24 h after the last administration.  Liver and blood (for serum extraction) were collected using standard methods. SAD-treated groups compared favorably (p>0.05) with control for organ-body weight ratio, liver and serum activities of aminotransferases, gamma-glutamate transferase, glutamate dehydrogenase, lactate dehydrogenase, sodium-potassium-adenosine triphosphatase, calcium-magnesium-adenosine triphosphatase, and serum globulin levels of subjects. However, SAD treatment showed significant effects (p<0.05) on liver and serum activities of alkaline phosphatase, serum protein, albumin and bilirubin levels. SAD treatment also showed mild effects on the hepatocytes but with no fatty degeneration. This study therefore provides evidence that long term therapeutic dose administration of SAD does not predispose to liver dysfunction in rats.