Toxicological and biochemical effects of therapeutic doses of chloroquine, artecxin, lonart and p-alaxin in P. berghei-infected mice: a comparative study

Abstract

Background: Alterations in hematological indices and biochemical parameters are implicated in malaria and many pharmacologic agents used in the treatment of malaria in the tropics.

Objective: This study was designed to determine and compare in vivo antimalarial activity and safety of therapeutic doses of Chloroquine (CQ), Artecxin (ART), P –Alaxin (P-ALA) and Lonart (LON) in Plasmodium berghei infected mice.

Method: Six groups each of five mice (healthy control (nonparasitized non-treated group), parasitized-non-treated (PnT), Parasitized- CQ treated (positive control), parasitized – ART, LON and P-ALA treated groups were used for the study. Antimalarial activity/parasite density in the blood of infected and treated mice was evaluated. Toxicity of drugs was also evaluated with haematological, biochemical parameters and histology.

Results: ART and other antimalarial drugs significantly (p<0.05) cleared the parasite density following three days administration of the drugs in the order ART>P-ALA>LON. The drugs ameliorated, malarial infection-induced abnormalities in hematological and biochemical indices. All the antimalarial drugs caused significant elevation (p<0.05) in plasma alkaline phosphatase (ALP) and aspartate amino transferase (AST) activities while ART showed no significant difference (p>0.05) in alanine amino transferase (ALT) activity when compared with control. Histopathological evaluation revealed severe necroinflammatory effect of ART on the liver cells while other drugs had mild toxic effects.

Conclusion: ART has a higher efficacy and antimalarial activity in Plasmodium berghei-infected mice compared to LON and P-ALA. However, its toxic effects on liver and kidney cells' architecture suggest that it be recommended in severe cases of malaria infection to preserve life.

Keywords:  Plasmodium berghei, Artecxin, Lonart, PAlaxin, Toxicity, Chloroquine