L-2-Oxothiazolidine-4-carboxylic acid reduces in vitro cytotoxicity of glucose degradation products

Abstract

The GDP-induced stimulation of free radicals in mesothelial cells in the present study may provide a possible mechanism of GDP cytotoxicity. Because OTZ reduced the toxic effects of GDP on mesothelial cells, this compound may improve biocompatibility of peritoneal dialysis fluids.

Antiglycation and Antioxidant Effect of Carnosine against Glucose Degradation Products in Peritoneal Mesothelial Cells

“…Peritoneal fluid bioincompatibility resulting from the presence of GDPs is one of main factors contributing to dialysis failure and loss of peritoneum in CAPD patients [7,8,9,10,11,12,13]. Several attempts have been developed to improve PD fluid biocompatibility through eliminating, minimizing or at least trapping GDPs.…”

“…Another possible mechanism is the ability of carnosine to quench reactive aldehydes such as acetaldehydes, formaldehyde, malondialdehyde (MDA), hydroxyalkenals and others [27, 29]. Many of these aldehydes are present in the heat-sterilized PDF, and other aldehydes like MDA and hydroxyalkenals are elaborated during incubation of HPMC with GDPs [11, 38]. Accordingly, the preventive effect of carnosine of HPMC protein modification may be related to the carnosine reaction with both GDPs present in dialysis fluid and the aldehydes generated as a result of cellular oxidative damage.…”

“…HPMC are the lining monolayer of the peritoneal cavity that provides a large surface of fluid movement and represents the ultimate target for attack by GDPs from the chronic exposure to PDF. The mechanism of toxicity involved is still unknown but it has been suggested to mediate reactive oxygen species (ROS) generation [11] and/or AGE formation [12]. In addition, GDPs are implicated in the stimulation of vascular endothelial growth factor from peritoneal cells, which may as a consequence increase peritoneum permeability and loss of ultrafiltration over time [13].…”

“…However, certain drawback may arise with each method allowing the possible presence of mini quantities of GDP in PDF that upon chronic use may develop significant adverse effects. Another approach is the application of additives of known antiglycation properties [11, 18]. Nevertheless, substantiating such substances may pose clinical or practical difficulties as a result of the high toxicity at the affecting dosing or the low shelf-life and stability in solution.…”

Prevention of membrane damage in patient on peritoneal dialysis with new peritoneal dialysis solutions

“…Morgan et al showed that various GDPs delay remesothelization of peritoneum in a scratch wound model of peritoneal repair and documented that the effect of GDPs was independent of the presence of glucose [37]. Breborowicz et al have shown that L-2-oxothiazolidine-4-carboxylic acid (a precursor for glutathione), reduces the GDP-induced stimulation of free radicals cytotoxicity of GDPs in human peritoneal mesothelial cells and argued that addition of L-2-oxothiazolidine-4-carboxylic acid in PDF may improve biocompatibility of PDF [38].…”