n(6)-(1-carboxyethyl)lysine and Kidney-Diseases

In this study, we investigated the role of carbonyl stress in gentamicin (GM)-induced renal injury in rats. Carbonyl stress is represented by methylglyoxal (MGO) and its downstream advanced glycation end products, such as N(ɛ)-(carboxyethyl)lysine (CEL). GM (150mg/kg/day, i.p.) administration for 6 days significantly increased blood urea nitrogen (BUN) levels from 24.06±0.55 to 85.04±21.31mg/dL and decreased creatinine clearance rate (Ccr) from 10.68±0.76 to 2.53±1.11ml/min/kg B.W.; biopsy showed tubular injury. The kidney levels of MGO and CEL increased significantly from 9.56±1.94 to 79.13±17.96μg/g of protein and from 0.03±0.00 to 0.06±0.00μmol/μg of protein, respectively. Therefore, MGO and CEL appeared to be associated with GM-induced renal damage. Co-administration of metformin (50 or 100mg/kg/day) and GM for 13 days effectively reversed GM-induced renal damage. The kidney levels of MGO and CEL decreased significantly from 24.95±7.74 to 22.98±17.74μg/g of protein and from 0.04±0.01 to 0.03±0.01μmol/μg of protein (both vs. the GM group), respectively. The identification of this new pathway may help prevent GM-induced nephrotoxicity.

Topics: Animals; Anti-Bacterial Agents; Antioxidants; Gentamicins; Glutathione; Immunohistochemistry; Kidney Diseases; Kidney Function Tests; Lysine; Male; Metformin; Pyruvaldehyde; Rats; Rats, Wistar

Advanced glycation end-products (AGE) have been involved in inflammatory diseases and may have an important role in the progression of symptoms. However, few studies have analysed the levels of glycated proteins in sepsis. In this study, we evaluated the levels of the well-known AGE (N(ε) -(carboxymethyl)lysine (CML) and N(ε) -(carboxyethyl)lysine (CEL)) in the plasma of septic patients.. Plasma from 36 patients admitted to an adult intensive care unit and 6 healthy controls had the levels of CML/CEL measured by ELISA.. The level of AGE in plasma decreased with the increase of severity (1·40±0·46 nmol/mg of protein in sepsis, 0·58±0·23 nmol/mg of protein in severe sepsis and 0·31±0·12 nmol/mg of protein in septic shock). Control plasma presented low AGE concentration (0·06±0·01 nmol/mg protein). Also, we found a decrease in plasma AGE in those patients that died at the end of 28 days follow-up (0·80±0·50 nmol/mg of protein in survivors vs. 0·31±0·10 nmol/mg of protein in nonsurvivors), being associated with the renal component of sequential organ failure assessment (SOFA) score. In the same line, there was a decrease in plasma AGE with the increase in SOFA.. Our data demonstrate that plasma AGE levels are inversely associated with the severity of sepsis and may be associated with kidney dysfunction.

Topics: Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Glycation End Products, Advanced; Humans; Kidney Diseases; Lysine; Male; Middle Aged; Prognosis; ROC Curve; Sepsis