Evaluation of Silybum marianum seed extract and vitamin B6 derivatives on methylglyoxal and sugar-induced oxidative DNA damage

Abstract

AbstractReducing sugars are known to generate reactive oxygen species (ROS), mainly by means of the glycation reaction. The hydroxyl radical, a prominent entity of ROS, is known to alter cellular DNA and induces damage to DNA, and plays a role in diseases such as diabetes mellitus. In this study, the oxidative damage of DNA induced by the lysine/Fe3+/MG reaction was investigated. Silybum marianum seeds extract (SlyE), standard silymarin (Sly), and vitamin B6 derivatives, pyridoxal-5-phosphate (PLP), pyridoxamine (PM), and pyridoxine (P) in reversing glycation-induced damage in DNA were evaluated. In addition, different sugars and sugar phosphates were incubated with plasmid pBR 322 DNA to control and compare their harmful effects. Our results revealed that SlyE protected lysine/Fe3+/MG induced oxidative DNA damage more effectively than Sly. Vitamins, on the other hand, prevented this DNA damage in the order of PLP>P>PM. The DNA altering and damaging intensity of sugars and sugar phosphates tested increased considerably in the following order: Ribose-5-phosphate > fructose-6-phosphate > ribose > fructose > fructose-1,6 biphosphate > glucose-6 phosphate > glucose. The results show that the lysine/Fe3+/MG glycation reaction can cause oxidative damage of DNA through a mechanism involving hydroxyl radicals. It also provides evidence that ribose-5-phosphate and fructose and its phosphate metabolites can alter DNA more rapidly in vitro than glucose and its phosphate metabolites.