Effects of a putrescine analog on Giardia lamblia

Abstract

The protozoan Giardia lamblia is the most frequent intestinal parasite of first-world countries and a major cause of waterborne disorder often referred to as traveler's diarrhea. We have previously noticed that the putrescine analog 1,4-diamino-2-butanone (DAB) remarkably inhibits the growth of anaerobic trichomonad and Trypanosoma cruzi parasites. Here, we examined the role of polyamines in Giardia cells using this putrescine analog. DAB impaired parasite proliferation dose-dependently. The analog induced increased flagella numbers and sometimes four ventral disks as well as asymmetrical division, indicating truncated or deregulated cytokinesis. Electron microscopy analysis revealed that DAB also triggered the encystment process. Oxidative stress was evaluated by measuring lipid peroxidation by thiobarbituric acid reactive substances (TBARS) detection. Trophozoites incubated either with 1 mM of DAB or putrescine for 18 h displayed increased lipoperoxide levels. Addition of 200 microM aminoguanidine, a polyamine/diamine oxidase inhibitor, partially reverted the DAB, but not the putrescine effects, indicating that the DAB effects are due, at least in part, to DAB oxidation end products. These data indicate that polyamines play a role in Giardia cell division, differentiation, and antioxidant defenses.

Leishmanicidal activity of Cecropia pachystachya flavonoids: Arginase inhibition and altered mitochondrial DNA arrangement

“…Here, it was shown mitochondrial damage and kDNA disorganization by transmission electron microscopy. These alterations maybe due to PA deficiency, as these polycations are antioxidant (Maia et al, 2008;Menezes et al, 2006;Tkachenko et al, 2011;Vannier-Santos et al, 2008) and can stabilize and regulate the function of nucleic acids (Igarashi and Kashiwagi, 2010). Such an inference is in agreement with that previously demonstrated by the effect of reduced PA synthesis in Trypanosoma cruzi (Menezes et al, 2006) and L. (L.) amazonensis (Vannier-Santos et al, 2008).…”

1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation

“…DAB, a diamino analogue of putrescine, is a competitive inhibitor of ODC in several pathogenic microorganisms such as T. cruzi [11], L. amazonensis [12], G. lamblia [13], Entamoeba invadens [40], Aspergillus nidulans [15], and Candida albicans [41]. Therefore, administration of millimolar DAB to several types of cells is expected to cause a significant decrease in polyamine contents, consequently leading to a notable decline in cell proliferation [11][12][13]. Accordingly, DAB reportedly promotes cell architecture disorganization, mitochondrial dysfunction, and increased lipid peroxidation [11,13].…”

“…Recently DAB has been reported to be toxic to several pathogens, including Trypanosoma cruzi, the etiologic agent of Chagas disease [11]. Other pathogenic microorganisms reported to be affected by DAB include Leishmania amazonensis [12], Giardia lamblia [13], and Tritrichomonas foetus [14]. It is thought that the major effect of DAB upon microorganisms is the inhibition of ornithine decarboxylase (ODC; K i =0.9 μM), the enzyme that catalyzes the first step in polyamine biosynthesis culminating in cell arrest [15,16].…”

Modes of Action of Arjunolic Acid and Derivatives on Trypanosoma cruzi Cells

“…Samples were fixed and postfixed as described above, dehydrated in ethanol series, dried by the critical point method in a Balzers apparatus, mounted on stubs and covered with a circa 20 nm-thick gold layer, as previously described [34]. Specimens were observed in a JEOL 5310 scanning electron microscope.…”