EFFECTS OF CHLOROQUINE, ARTHEMETER-LUMEFANTRINE AND ARTESUNATE ON EXPERIMENTAL COLITIS IN RATS

Abstract

Ulcerative colitis is a chronic inflammatory bowel disease characterised by inflammation, ulceration and bleeding of the colonic mucosa. The etiology is still unknown. Studies have shown that some anti-malarial drugs interfere with gastric mucosal integrity, leading to the development of gastric ulceration. However the effect of this class of drugs on the integrity of the colon is not known. This study was designed to investigate the effects of chloroquine, artesunate and artemether-lumefantrine on acute ulcerative colitis in rats. Eighty male albino rats (160–180 g) were randomly assigned to four groups of twenty animals each viz: control (distilled water), chloroquine phosphate (8 mg/kg), artemether-lumefantrine combination (8 mg/kg) and artesunate (2 mg/kg) p.o. Five days post-treatment, colitis was induced by intrarectal administration of 6% acetic acid (1mL/200 g). Colonic mucosal injury was assessed using a macroscopic diarrhoea score scale. Lipid peroxidation in the colon was determined by measuring the levels of Thiobarbituric Acid Reactive Substances using spectrophotometry. Histological findings were derived from paraffin sections of the colonic tissue stained with haematoxylin and eosin and scored according to the degree of neutrophil infiltration and tissue damage. The readings were taken over the period of 12 days post- induction in order to monitor the healing rate. Data were analysed using Student’s t test at p= 0.05. The diarrhoea score in the control group was 2.4 ± 0.1 and 1.1 ± 0.3 for days 3 and 12 post- induction respectively. These scores were significantly increased by chloroquine (3.1 ± 0.3 and 2.0 ± 0.0) and decreased by artesunate (1.6 ± 0.3 and 0.8 ± 0.2) respectively. Artemether-lumefantrine combination did not affect the diarrhoea score significantly. Colonic lipid peroxidation in the artesunate treated rats was significantly lower than the control, chloroquine vii and artemether-lumefantrine values throughout the healing period (3.1 ± 0.1 and 2.4 ± 0.1μmol/mL, 4.4 ± 0.1 and 3.61 ± 0.2 μmol/mL, 4.8 ± 0.1 and 4.4 ± 0.3 μmol/mL and 4.7 ± 0.2 and 3.8 ± 0.2 μmol/mL at days 3 and 12 for all the groups respectively), suggesting an interference with colon oxidative system. High rate of colonic injury and inflammatory cell infiltration were observed in the untreated colitis-induced animals (Infiltration score = 4.0 ± 0.2 on day 12). Treatment with chloroquine and artemether-lumefantrine did not significantly change the infiltration score when compared with the control values. However, artesunate reduced inflammatory cell infiltration (Infiltration score of 1.4 ± 0.4) with less severe ulceration at the same reference period. Chloroquine and artemether-lumefantrine delayed healing of acetic acid-induced colitis, while artesunate accelerated the process. The use of chloroquine and artemeter-lumefantrine for malaria treatment in colitis patients may not be advisable.