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1. Introduction
Gentamicin (GM) is commonly applied in human clinical practices for treatment of life-threatening gram-negative infections [1, 2]. However, the usefulness of GM is limited by the development of nephrotoxicity. In some cases, this side effect is so severe that the use of the drug must be discontinued. In spite of the introduction of newer and less toxic antibiotics, GM is still used clinically because of its rapid bactericidal action, broad-spectrum activity, chemical stability, and low cost [3, 4]. GM-induced nephrotoxicity is characterized by direct tubular necrosis, without morphological changes in glomerular structures [1]. The mechanisms involved in GM-induced cell injury are not clearly understood. However, several studies demonstrated that reactive oxygen species (ROS) may be important mediators in GM-induced nephrotoxicity [5]. Abnormal production of ROS directly damages some macromolecules and induces cellular injury and necrosis via several mechanisms including peroxidation of membrane lipids, protein denaturation, and DNA damage [6, 7]. Accordingly, the administration of several compounds with antioxidant activity has been successfully used to prevent or ameliorate GM-induced nephrotoxicity [8, 9].
In the past few years, much interest has been laid on the role of naturally occurring dietary substances for the control and management of various chronic diseases, one such compound salicylic acid (SA) has been used since ancient times to provide pain relief and treat inflammatory conditions. Salicylic acid is a phenolic compound present in plants, where it plays a central role in the development of local and systemic resistance to pathogen infection [10, 11]. Humans and animals obtain SA mainly from daily foods, fruits, and vegetables. Increasing evidence demonstrates that applied SA can counteract oxidative damage induced by adverse conditions in animals [12, 13], though the mechanisms underlying these effects remain unclear. It has been reported that SA comprise free radical-scavenging and iron chelation properties [14]. SA can affect the activation of transcription factors, in particular nuclear factor kappa B (NF-κB), thereby intervening in apoptotic pathways [15]. It is also a hydroxyl radical scavenger in both experimental animals and humans who are experiencing oxidative stress [16, 17].
The aim of the present study was therefore to investigate whether SA treatment prevents GM-induced nephrotoxicity. For this purpose, we have examined histopathological effects of GM and possible protective effect of SA...