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.The aminoglycoside antibiotics are used, either alone or in combination with cell wall-active agents, for the treatment of severe ⁄ life-threatening infections caused by Gram-positive and Gram-negative aerobes [1]. Gentamicin (GM) is probably the most commonly used and studied of all the aminoglycosides [2]. One serious limitation to the use of this antibiotic is that it can cause ototoxicity and nephrotoxicity, and, in some situations, these side effects are so severe that the use of the drug must be discontinued. It has been estimated that up to 30% of patients treated with GM for more than 7 days show some signs of renal impairment [3]. GM nephrotoxicity has been investigated in several experimental models in rabbits, mice and rats [4][5][6], and several strategies and agents have been used, with various degrees of success, in an attempt to protect or reverse renal GM damage [3,7,8]. This would be expected to have important clinical implications in increasing the safety of the drug. Because the pharmaceutical industry, in general, is not investing adequately in the development of new antibiotics, and antimicrobial resistance is on the increase, revival of older antibiotics for use might be a viable option. Some reviews have been published recently on specific aspects of GM nephrotoxicity. For example, Zorov [9] wrote about the role of renal mitochondria on protection against GM nephrotoxicity. Koyner...