ANTIOXIDANTS MODULATE ADENOSINE METABOLISM IN RAT MESANGIAL CELLS CULTURED UNDER HIGH GLUCOSE CONDITIONS

Abstract

Glomerular mesangial cells play a major role in glomerular hemodynamics, considered also as antigen-presenting cells participating in immune response. Mesangial dysfunction and proliferation are typical lesions of diabetic glomerulopathy. Adenosine, a local hormone, produced by mesangial cells is a metabolic regulator of renal blood flow, capable of decreasing glomerular filtration rate (GFR), exerting immunosuppressive, antiproliferative and anti-inflammatory properties. Since it was well established that antioxidants confer protection against increased oxidative stress that occurs in diabetes, the effect of captopril, reduced glutathione and melatonin on adenosine metabolism was investigated. Glomerular mesangial cells obtained from collagenase treated glomeruli, isolated from renal cortex of Sprague-Dowley rats, were grown under high glucose conditions (30 mmol/L) as a model of diabetic microenvironment. The activity of adenosine metabolizing enzymes: 5′-nucleotidease (5′-NU) responsible for its production and adenosine deaminase (ADA)—responsible for its degradation were investigated. Hyperglycemic conditions led to decreased adenosine production via 5′-NU and decreased removal via ADA. Captopril, given in therapeutic concentration induced enzyme activities in normoglycemic conditions and restored hyperglycemia—induced decrease. In order to investigate if the presence of SH groups may be responsible for this improvement, the cells were exposed to reduced glutathione, and it exerted almost equal effect, given in physiological and higher concentrations. Melatonin increased 5′-NU activity only in physiological glucose conditions. Presented results confirm potential renoprotective effect of SH-group containing antioxidant supplementation during diabetes in restoring adenosine metabolism.