Lipid peroxidation is associated with poor control of type-2 diabetes mellitus.

BACKGROUND: Hyperglycemia increases oxidative stress through the overproduction of reactive oxygen species, which results in an imbalance between free radicals and the antioxidant defense system of the cells. A positive correlation was reported between lipid peroxide levels and diabetic complication. OBJECTIVES: The aim of the present study was to investigate the state of oxidative stress in controlled and uncontrolled diabetic patients. METHODS: One hundred thirty nine participants were included in this study, grouped as: Group-I: Healthy Control group of non-diabetic normal subjects, Group-II: Controlled type-2 DM group of subjects with type-2 DM and HbA1c≤8% and Group-III: Uncontrolled type-2 DM group of subjects with type-2 DM and HbA1c>8%. Fasting blood glucose, 2h postprandial glucose, MDA and HbA1c were quantified. The association between diabetic control and lipid peroxidation (malondialdehyde) was evaluated. RESULTS: The mean HbA1c increased significantly in uncontrolled type-2 DM subjects compared to controlled type-2 DM group. Lipid peroxidation as expressed in MDA was significantly increased in uncontrolled type-2 DM group compared to controlled type-2 DM, both groups show significant elevation in this parameter compared to healthy subjects. There is a significant positive correlation between MDA and HbA1c in the studied subjects. CONCLUSION: The core problem during diabetes is poor glycemic control, which leads to protein glycation, lipid peroxidation, oxidative stress and finally varieties of complications. Periodic evaluation of lipid peroxidation products in diabetes mellitus is recommended as it could contribute to the early identification and management of oxidative stress.

Influence of combinations of digitonin with selected phenolics, terpenoids, and alkaloids on the expression and activity of P-glycoprotein in leukaemia and colon cancer cells.

P-glycoprotein (P-gp or MDR1) is an ATP-binding cassette (ABC) transporter. It is involved in the efflux of several anticancer drugs, which leads to chemotherapy failure and multidrug resistance (MDR) in cancer cells. Representative secondary metabolites (SM) including phenolics (EGCG and thymol), terpenoids (menthol, aromadendrene, ß-sitosterol-O-glucoside, and ß-carotene), and alkaloids (glaucine, harmine, and sanguinarine) were evaluated as potential P-gp inhibitors (transporter activity and expression level) in P-gp expressing Caco-2 and CEM/ADR5000 cancer cell lines. Selected SM increased the accumulation of the rhodamine 123 (Rho123) and calcein-AM (CAM) in a dose dependent manner in Caco-2 cells, indicating that they act as competitive inhibitors of P-gp. Non-toxic concentrations of ß-carotene (40µM) and sanguinarine (1µM) significantly inhibited Rho123 and CAM efflux in CEM/ADR5000 cells by 222.42% and 259.25% and by 244.02% and 290.16%, respectively relative to verapamil (100%). Combination of the saponin digitonin (5µM), which also inhibits P-gp, with SM significantly enhanced the inhibition of P-gp activity. The results were correlated with the data obtained from a quantitative analysis of MDR1 expression. Both compounds significantly decreased mRNA levels of the MDR1 gene to 48% (p<0.01) and 46% (p<0.01) in Caco-2, and to 61% (p<0.05) and 1% (p<0.001) in CEM/ADR5000 cells, respectively as compared to the untreated control (100%). Combinations of digitonin with SM resulted in a significant down-regulation of MDR1. Our findings provide evidence that the selected SM interfere directly and/or indirectly with P-gp function. Combinations of different P-gp substrates, such as digitonin alone and together with the set of SM, can mediate MDR reversal in cancer cells.