Circulating glycolaldehyde induces oxidative damage in the kidney of rats

Abstract

Renal failure is a key pathological issue in diabetic patients. Increased levels of advanced glycation end-products (AGEs) have been associated to diabetic complications, including diabetic nephropathy. Models of AGE-treated animals have been applied to evaluate the effect of such molecules on oxidative parameters involved in the pathogenesis and evolution of diabetes disease. However, little is known about the effect of glycating agents other than glucose. Here we investigate the effect of intravenously administrated glycolaldehyde (GA) on oxidative stress parameters of the kidney. Male Wistar rats received a single injection of GA in different doses (10, 50 or 100mg/kg) and were sacrificed after 6, 12 or 24h. Activities of antioxidant enzymes catalase, superoxide dismutase and glyoxalase I were assayed. Damage to proteins and lipids were also assayed. The content of N(epsilon)-(carboxymethyl)lysine (CML) was quantified. Glycolaldehyde induced a decrease in the activity of all enzymes studied. Lipoperoxidation and protein carbonylation raised, accompanied by a decrease in sulfhydryl groups. Despite the oxidative stress generated by GA, no change was found in the content of CML, suggesting that accumulation of AGEs in the kidney might occur at later steps in the development of diabetic nephropathy.

Glycolaldehyde Induces Cytotoxicity and Increases Glutathione and Multidrug-Resistance-Associated Protein Levels in Schwann Cells

“…8,29,30) In breast cancer cells, GA increased intracellular superoxide production and MnTMPyP, a superoxide dismutase/catalase mimetic, failed to protect cells from the GA-induced apoptotic cell death. 16,31) Studies have indicated that GA is oxidized by ROS, such as superoxide, during oxidative stress in isolated hepatocytes to form glyoxal and glyoxal subsequently induces cytotoxicity.…”

“…1,2) Although plasma GA level has not been quantified, its physiological concentration is estimated to range from 0.1 to 1 mm [8][9][10][11] and several in vitro studies have employed that range. [9][10][11] In this study, we demonstrated for the first time that GA at near-physiological concentration exerted biological effects on Schwann cells by effectively decreasing cell viability (Fig.…”

“…Schwann cells were treated with GA (100, 250 or 500 µm) for various times (4,8,16, or 24 h) and cell viability was measured by the MTS assay (Fig. 1A).…”

“…Nonetheless, its physiological concentration is estimated to range from 0.1 to 1 mm. [8][9][10][11] Although the physiological purpose of the intensive production of GA is unclear, it is postulated that the elevated GA is involved in the development of diabetic complications.…”

The association effect of insulin and clonazepam on oxidative stress in liver of an experimental animal model of diabetes and depression

“…GLO plays an important role in the detoxification of aoxoaldehydes, mainly glyoxal and MG (Lorenzi et al, 2010). This enzyme catalyzes the formation of S-D-lactoylglutathione from MG and GSH, leading to reduced concentrations of its substrate.…”