Experimental Gentamicin Nephrotoxicity and Agents that Modify it

A Mini-Review of Recent Research

Badreldin H. Ali, Mohammed Al Za'abi, Gerald Blunden, Abderrahim Nemmar

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

The aminoglycoside antibiotic gentamicin (GM) is still widely used against infections by Gram-positive and Gram-negative aerobic bacteria. Its therapeutic efficacy, however, is limited by renal impairment that occurs in up to 30% of treated patients. The drug may accumulate in epithelial tubular cells causing a range of effects starting with loss of the brush border in epithelial cells and ending in overt tubular necrosis, activation of apoptosis and massive proteolysis. GM also causes cell death by generation of free radicals, phospholipidosis, extracellular calcium-sensing receptor stimulation and energetic catastrophe, reduced renal blood flow and inflammation. Many drugs have been shown to either ameliorate or potentiate GM nephrotoxicity. This article aims at updating the literature that has been published in the past decade on the effects of agents that either ameliorate or augment the nephrotoxicity of this aminoglycoside. Notable among the new ameliorating procedures are gene therapy, such as intravenous cell therapy with serum amyloid A protein-programmed cells, and the use of some novel antioxidant agents and oils of natural origin. These include, for example, green tea, garlic saffron, grape seed extracts as well as sesame and oleanolic oils. Agents that may augment GM nephrotoxicity include indomethacin, cyclosporin, uric acid and the Ca ++-channel blocker verapamil. Most of the nephroprotective agents mentioned here have not been tested in large controlled clinical trials. Because of their relative safety and effectiveness, antioxidant agents seem to be good candidates for testing in humans.

Original languageEnglish
Pages (from-to)225-232
Number of pages8
JournalBasic and Clinical Pharmacology and Toxicology
Volume109
Issue number4
DOIs
Publication statusPublished - Oct 2011

Fingerprint

Gentamicins
Aminoglycosides
Research
Gram-Negative Aerobic Bacteria
Antioxidants
Grape Seed Extract
Epithelial Cells
Sesame Oil
Calcium-Sensing Receptors
Oils
Serum Amyloid A Protein
Garlic
Aerobic bacteria
Renal Circulation
Proteolysis
Controlled Clinical Trials
Tea
Microvilli
Cell- and Tissue-Based Therapy
Verapamil

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Experimental Gentamicin Nephrotoxicity and Agents that Modify it : A Mini-Review of Recent Research. / Ali, Badreldin H.; Al Za'abi, Mohammed; Blunden, Gerald; Nemmar, Abderrahim.

In: Basic and Clinical Pharmacology and Toxicology, Vol. 109, No. 4, 10.2011, p. 225-232.

Research output: Contribution to journalArticle

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