Article 2022 · 2 atıf

Toxicity of Glycyl-l-Prolyl-l-Glutamate Pseudotripeptides: Cytotoxic, Oxidative, Genotoxic, and Embryotoxic Perspectives

Turkez, Hasan, Tozlu, Ozlem Ozdemir, Tatar, Arzu, Arslan, Mehmet Enes, Cadirci, Kenan, Marinelli, Lisa, Yapca, Omer Erkan, Cacciatore, Ivana, Di Stefano, Antonio, Mardinoglu, Adil

Özet

The tripeptide H-Gly-Pro-Glu-OH (GPE) and its analogs began to take much interest from scientists for developing effective novel molecules in the treatment of several disorders including Alzheimer's disease, Parkinson's disease, and stroke. The peptidomimetics of GPEs exerted significant biological properties involving anti-inflammatory, antiapoptotic, and anticancer properties. The assessments of their hematological toxicity potentials are critically required for their possible usage in further preclinical and clinical trials against a wide range of pathological conditions. However, there is so limited information on the safety profiling of GPE and its analogs on human blood tissue from cytotoxic, oxidative, and genotoxic perspectives. And, their embryotoxicity potentials were not investigated yet. Therefore, in this study, measurements of mitochondrial viability (using MTT assay) and lactate dehydrogenase (LDH) release as well as total antioxidant capacity (TAC) assays were performed on cultured human whole blood cells after treatment with GPE and its three novel peptidomimetics for 72 h. Sister chromatid exchange (SCE), micronucleus (MN), and 8-oxo-2-deoxyguanosine (8-OH-dG) assays were performed for determining the genotoxic damage potentials. In addition, the nuclear division index (NDI) was figured out for revealing their cytostatic potentials. Embryotoxicity assessments were performed on cultured human pluripotent NT2 embryonal carcinoma cells by MTT and LDH assays. The present results from cytotoxicity, oxidative, genotoxicity, and embryotoxicity testing clearly propounded that GPEs had good biosafety profiles and were trouble-free from the toxicological point of view. Noncytotoxic, antioxidative, nongenotoxic, noncytostatic, and nonembryotoxic features of GPE analogs are worthwhile exploring further and may exert high potentials for improving the development of novel disease-modifying agents.

Anahtar Kelimeler

N-TERMINAL TRIPEPTIDE GLYCINE-PROLINE-GLUTAMATE GROWTH-FACTOR-I GPE ANALOGS GLU GPE LYMPHOCYTES BRAIN VITRO INFLAMMATION ANTIOXIDANT

WoS Kategorileri

Toxicology

Sürdürülebilir Kalkınma Amaçları

Sağlık ve Kaliteli Yaşam

Künye

Dergi: JOURNAL OF TOXICOLOGY
Yıl: 2022
Cilt: 2022
ISSN: 1687-8191
eISSN: 1687-8205
DOI: 10.1155/2022/3775194
WoS UID: WOS:000891074400001

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