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Toxicology letters

Gentamicin caused renal injury deeply related to methylglyoxal and N(ɛ)-(carboxyethyl)lysine (CEL).


PMID 23454834

Abstract

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.