Gentamicin caused renal injury deeply related to methylglyoxal and Ne{open}-(carboxyethyl)lysine (CEL)

Yi Chieh Li, Yi Min Shih, Jen Ai Lee

Research output: Contribution to journalArticle

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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 Ne{open}-(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.

Original languageEnglish
Pages (from-to)85-92
Number of pages8
JournalToxicology Letters
Volume219
Issue number1
DOIs
Publication statusPublished - May 2013

Fingerprint

Pyruvaldehyde
Gentamicins
Lysine
Kidney
Wounds and Injuries
Proteins
Advanced Glycosylation End Products
Biopsy
Metformin
Blood Urea Nitrogen
Urea
Rats
Creatinine
Blood
Nitrogen

Keywords

  • Aminoglycoside
  • Gentamicin
  • Kidney damage
  • Metformin
  • Methylglyoxal
  • N-(carboxyethyl)lysine

ASJC Scopus subject areas

  • Toxicology

Cite this

Gentamicin caused renal injury deeply related to methylglyoxal and Ne{open}-(carboxyethyl)lysine (CEL). / Li, Yi Chieh; Shih, Yi Min; Lee, Jen Ai.

In: Toxicology Letters, Vol. 219, No. 1, 05.2013, p. 85-92.

Research output: Contribution to journalArticle

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