Abstract
The syndrome of uremic toxicity comprises a complex toxic milieu in-vivo, as numerous uremic substances accumulate and harm the organ systems. Among these substances, toxic and non-toxic players differently interfere with human cells. However, results from animal experiments are not always compatible with the expected reactions in human patients and studies on one organ system are limited in capturing the complexity of the uremic situation. In this narrative review, we present aspects relevant for cellular toxicity research based on our previous establishment of a human spermatozoa-based cell model, as follows: (i) applicability to compare the effects of more than 100 uremic substances, (ii) detection of the protective effects of uremic substances by the cellular responses towards the uremic milieu, (iii) inclusion of the drug milieu for cellular function, and (iv) transferability for clinical application, e.g., hemodialysis. Our technique allows the estimation of cell viability, vitality, and physiological state, not only restricted to acute or chronic kidney toxicity but also for other conditions, such as intoxications of unknown substances. The cellular models can clarify molecular mechanisms of action of toxins related to human physiology and therapy. Identification of uremic toxins retained during acute and chronic kidney injury enables further research on the removal or degradation of such products.
Highlights
Human cell models must be developed alongside the disease of interest
This commentary article presents aspects based on a human spermatozoa model that can help to create further cell models relevant for the investigation of clinical toxicity, such as in uremia
We favor to study the uremic milieu with the following parameters: (i) inclusion of a wide number of uremic substances, (ii) selection of a cellular readout that extends toxic versus non-toxic categories, (iii) consideration of the treatment of the patients, i.e., drugs, and (iv) early translation in order to improve hemodialysis
Summary
Human cell models must be developed alongside the disease of interest. The syndrome of uremic toxicity includes complex variables to be considered for creating in-vitro conditions adequate to the uremic state. Our team developed a human spermatozoa-based model for the evaluation of toxic effects on cell viability and cell motility [6]. The use of the progressive motility of animal-derived spermatozoa as a method to identify the toxic effects of substances has been previously implemented [18,19,20]. The availability of robust human motility test systems that allow for a broad and serial substance evaluation for putative toxic effects on mitochondrial function is limited. The integration of cellular viability with its functional response allows for a more stringent resemblance of the uremic toxicity situation This narrative review aims to give general guidance for the establishment of cellular toxicity models. The cellular motility analysis allows us tous detect the protective effects of the of the substances according to the previously established method (2).
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