title: Gentamicin caused renal injury deeply related to methylglyoxal and N(ɛ)-(carboxyethyl)lysine (CEL).
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.
authors: School of Pharmacy, College of Pharmacy, Taipei Medical University, No. 250, Wuxing Street, Taipei 11031, Taiwan, ROC. d301097002@tmu.edu.tw
authors: Yi-Chieh
authors: YC
authors: Li
authors: Yi-Min
authors: YM
authors: Shih
authors: Jen-Ai
authors: JA
authors: Lee
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism; D005839:Gentamicins / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007677:Kidney Function Tests; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000494:pharmacology; D011765:Pyruvaldehyde / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D005839:Gentamicins; C054688:N(6)-(1-carboxyethyl)lysine; D011765:Pyruvaldehyde; D008687:Metformin; D005978:Glutathione; D008239:Lysine