Dose-Dependent Alterations in the Biomarkers of Lipid and Protein Oxidation in the Blood of Patients with Type 2 Diabetes Mellitus after in vitro Incubation with Extracts of Chelidonium majus L.

Abstract

The role of oxidative stress in the occurrence and development of diabetes mellitus is both critical and pivotal. Several molecular event cascades in different metabolic pathways such as glycolytic, hexosamine, protein kinase C, polyol and advanced glycation end-product pathways have been identified as pro-oxidative processes and are usually upregulated in diabetics. Consistent with our previous studies, we continue to evaluate the antioxidant potential of great celandine (Chelidonium majus L., CM), a representative of the Papaveraceae family, collected from northern parts of Poland using the blood samples of patients with type 2 diabetes mellitus. Therefore, in the present study, oxidative stress biomarkers (2-thiobarbituric acid reactive substances (TBARS), aldehydic and ketonic derivatives of oxidative modification of proteins (OMP)) were used to evaluate the antioxidant properties of the stalk and root extracts of CM in final doses of 5 mg.mL^-1, 2.5 mg.mL^-1, 1.25 mg.mL^-1 and 0.63 mg.mL^-1. Plant materials were collected from natural habitats on the territory of the Kartuzy district in the Pomeranian province (northern part of Poland). The use of extracts derived from both roots and stalks of CM collected from both urban and rural agglomerations in final doses of 5 mg.mL^-1, 2.5 mg.mL^-1, and 1.25 mg.mL^-1 resulted in a significant enhancement of lipid peroxidation in the blood samples. On the contrary, only incubation of blood samples with stalk extracts of CM collected from urban areas at a final dose of 0.63 mg.mL^-1 resulted in a no-significant decrease in TBARS levels contributing to the protection of lipid structures in membranes. Similar results were obtained by analyzing levels of aldehydic derivatives of oxidatively modified proteins in the blood samples after in vitro incubation with the extracts, where final doses of 5 mg.mL^-1, 2.5 mg.mL^-1, and 1.25 mg.mL^-1 significantly increased the oxidation process in protein structures. Analysis of levels of ketonic derivatives of oxidatively modified proteins showed that the use of root extracts of CM collected from urban agglomerations in final doses of 2.5 and 1.25 mg.mL^-1 reduced levels of oxidatively modified proteins, while the use of stalk extracts of CM harvested from urban agglomerations in a final dose of 0.63 mg.mL^-1 statistically significantly reduced levels of ketonic derivatives of oxidatively modified proteins compared to the control samples. These in vitro studies indicate that extracts derived from this plant are a significant source of natural metabolites that could be cytotoxic in final doses of 5 mg.mL^-1, 2.5 mg.mL^-1, and 1.25 mg.mL^-1 to the blood of patients with T2DM. Only a final dose of 0.63 mg.mL^-1 no significantly changed levels of lipid and protein oxidation in the blood samples.