*Cell Death after Photodynamic Therapy Treatment in Unicellular Protozoan Parasite… DOI: http://dx.doi.org/10.5772/intechopen.94140*

endoplasmic reticulum seen in close contact with abnormal hydrogenosomes [2]. Furthermore, parasites treated with proteossome inhibitors exhibit the appearance of an uncommon enlarged endoplasmic reticulum and concentric membrane whorls, which resembled autophagic vacuoles [24]. The round-shaped mebendazole-treated parasites presented an intense cytoplasmic vacuolization, and profiles of endoplasmic reticulum were frequently seen in association with abnormal hydrogenosomes and vacuoles [23]. Another autophagy way can be necessary for caspases activation and induction of apoptosis in trichomonads. However, cellular death induced by griseofulvine in trichomonad seems to not involve the path of caspases autophagy way. Since both the mechanisms, apoptosis and autophagy, can lead to release of lysosomal components after treatment of *T. foetus* with PDT [44], it is not known which of these mechanisms the parasite is using in different treatments.

The absence of apoptotic bodies and the characterization of a non-apoptotic-like cell death which fails to fulfill the criteria for apoptosis suggest paraptosis mechanism, once the cell death features shown by lycorine treatment in *T. vaginalis* differ from the apoptosis-like characteristics reported for this protist [2]. Although *T. foetus* presents some morphological aspects similar to apoptosis such as nuclear fragmentation and chromatin condensation, it also features aspects of paraptosis such as cytoplasmic vacuolization and chromatin condensation [6]. The main feature of paraptosis consists of extensive cytoplasmic vacuolation without significant cell membrane blebbing, nuclear shrinkage, or pyknosis. To date the most defining feature that differentiates it from autophagic cell death is the absence of autophagic vacuoles in paraptosis (**Table 1**) [29, 30, 42, 47].

Although, recent studies showed the "ladder pattern" compatible internucleosomic genomic DNA fragmentation characteristic of apoptosis, in *T foetus* submitted to PDT treatment (unpublished data).

The different treatments and the different results obtained with *T. foetus* suggest the existence of more than one mechanism of cell demise in these parasites (**Figure 1**).

#### **6. Implications and future directions**

The evidence of that alternative, non-apoptotic, PCD in unicellular organisms has important implications for understanding cell dynamics. The environmental stimuli can produce different types of cell death depending on the intensity of stimulus, and that classic apoptosis and necrosis may represent only two extremes of a continuum intermediate form of cell death, applicable to also unicellular organisms [10]. Comparatives analyses of proteome maps from parasites exhibiting such pathogenic characteristics may provide valuable data to understand the pathogenic mechanisms involved in urogenital trichomoniasis. Besides, the metabolic pathways that are different from those of their mammal hosts, given that Trichomonads possesses a hydrogenosomal/cytosolic compartmentalization of metabolism and metabolic pathway, the identification of proteins involved in such metabolic pathways could reveal good targets for drugs development [1, 48].

Several laboratories have contributed to understand the protein expression of Trichomonads, but despite numerous research and efforts to unravel the mechanisms of cell death, detailed description of the molecular mechanisms is still unknown. Identification of proteins related to the machinery of death of these cells should be the main focus of studies in the coming years. Studies related to molecular biology and biochemistry are still needed because little is known about the overall proteomic expression profiling of this parasite.

*Cell Death after Photodynamic Therapy Treatment in Unicellular Protozoan Parasite… DOI: http://dx.doi.org/10.5772/intechopen.94140*
