Efficacy of combination therapy (metronidazole and/or artemether) in experimental giardiasis and its impact on nonenzymatic oxidative stress biomarkers

Abstract

BackgroundGiardia lamblia trophozoites colonize in the upper small intestine resulting in diarrhea and various clinical manifestations, including abdominal pain, anorexia, and signs of malabsorption. A decrease in the level of trace elements might occur because of this absorption deficiency resulting from giardiasis. Experimentally, the excretory secretory product of G. lamblia trophozoites increased the level of reactive oxygen species in mice enterocytes. The levels of bilirubin, uric acid, and albumin are often used as major nonenzymatic oxidative biomarkers.ObjectiveThis study was designed to determine the effect of therapy by metronidazole (MTZ) and artemether (ART) on trophozoite and cyst forms in experimentally Giardia spp.-infected hamsters and to reveal the changes in iron (Fe), manganese (Mn), copper (Cu), and chromium (Cr) serum levels pretreatment and post-treatment. Another objective was to evaluate the impact of this therapy on serum levels of bilirubin, uric acid, and albumin as nonenzymatic oxidative stress biomarkers.Materials and methodsHamsters were divided into four groups: the control group I included two subgroups, Ia (noninfected, nontreated) and Ib (infected, nontreated); group II (infected and treated with MTZ); group III (infected and treated with ART); and group IV (infected and treated with combined therapy of MTZ+ART). Hamsters of all four groups were killed 5 weeks postinfection (PI) - that is, 2 weeks after treatment - to evaluate drug efficacy. Stool samples and duodenal contents were examined to count the number of G. lamblia cysts and trophozoites, respectively. Blood samples were also collected to estimate trace elements (Fe, Mn, Cu, and Cr) as well as nonenzymatic oxidative stress biomarkers (bilirubin, uric acid, and albumin).ResultsThere was a significant reduction in trophozoite and cyst counts following treatment with ART alone (88 and 82.5%, respectively) as compared with the infected control group Ib. Treatment with MTZ alone and in combination with ART also yielded a very high percentage of reduction in both trophozoites (94.2 and 98.3%, respectively) and cysts counts (93.9 and 95.5%, respectively). The trace elements in serum of infected controls (Ib) displayed nonsignificant decrease in Fe and significant decrease in Mn levels as compared with their levels in noninfected hamsters of group Ia. Cu levels increased in the infected group and were still increased after treatment with either MTZ or ART but decreased to normal with the combined therapy. Cr levels showed no significant change in all groups. Uric acid increased in infected controls as compared with normal controls. Treatment with MTZ or ART alone decreased uric acid levels lower than normal, and the combination of both drugs normalized its levels. Evaluation of serum bilirubin levels in the infected group and in those treated by MTZ and ART alone did not show any statistically significant differences compared with the normal noninfected group. Treatment with the combined therapy yielded even slightly lower insignificant level. Albumin level also did not differ significantly except in the combined regimen where it was lower than the normal range.ConclusionThe effect of giardiasis on the changes in the level of trace elements and nonenzymatic oxidative stress biomarkers is relevant in this study. The combined therapy produced significant parasite eradication and normalized the studied parameters with the exception of Mn and albumin levels, which were adversely affected and remained lower than normal. Further studies are needed to evaluate these data in undernourished and chronically infected hamsters.