ORIGINAL ARTICLE Flavocoxid attenuates gentamicin-induced nephrotoxicity in rats Dalia H. El-Kashef 1 & Asmaa E. El-Kenawi 1 & Ghada M. Suddek 1 & Hatem A. Salem 1 Received: 6 July 2015 /Accepted: 2 August 2015 # Springer-Verlag Berlin Heidelberg 2015 Abstract Gentamicin is a widely used antibiotic against serious and life-threatening infections; however, its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine whether flavocoxid has a protective effect against gentamicin-induced nephrotoxicity in rats. For this pur- pose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of flavocoxid on gentamicin induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was determined. Twenty-four male Wistar albino rats were randomly divided into three groups, namely control, gentamicin (100 mg/kg, i.p.) and gentamicin plus flavocoxid (20 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood, urine samples and kidneys were collected for further analysis. Gentamicin administration caused a severe nephrotoxicity which was evidenced by an ele- vated renal somatic index (RSI), serum creatinine, blood urea nitrogen, serum lactate dehydrogenase, and protein in urine with a concomitant reduction in serum albumin and normalized cre- atinine clearance value as compared with the controls. Moreover, a significant increase in renal contents of malondialdehyde, myeloperoxidase, and tumor necrosis factor-alpha with a signif- icant decrease in renal reduced glutathione and superoxide dis- mutase activities was detected upon gentamicin administration together with increasing the sensitivity of isolated urinary bladder rings to ACh. Exposure to gentamicin induced necrosis of renal tubular epithelial cells. Flavocoxid protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by gentamicin treatment. In addition, flavocoxid significantly reduced the responses of isolated bladder rings to ACh. The results from our study indicate that flavocoxid supplement atten- uates gentamicin-induced renal injury via the amelioration of oxidative stress and inflammation of renal tubular cells. Keywords Gentamicin . Flavocoxid . Nephrotoxicity . Urinary bladder . TNF-α . Nitric oxide Introduction Gentamicin is an aminoglycoside antibiotic which is com- monly used for the treatment of serious infections caused by Gram-negative bacteria. Although it is a powerful antibacteri- al (Chen and Kaye 2011), its nephrotoxic and ototoxic side effects can be quite severe that its use has to be discontinued. It has been estimated that up to 30 % of patients treated with aminoglycosides for more than 7 days show some signs of nephrotoxicity (Mattew 1992 ) and the specificity of gentamicin-induced renal toxicity is related to its preferential accumulation in the renal convoluted tubules and lysosomes (Nagai and Takano 2004). Nephrotoxicity induced by genta- micin is a complex situation characterized by an increase in blood urea nitrogen (BUN) and serum creatinine concentra- tion, and tubular necrosis (Parlakpinar et al. 2005). Reactive oxygen species (ROS) including superoxide an- ion, hydrogen peroxide, and singlet oxygen act as messengers in complex processes such as gene expression and regulation of cell proliferation when they are excessively generated or when enzymatic and non-enzymatic defense systems are im- paired (Nazıroğlu 2007). There is also evidence that ROS play an important role in the pathogenesis of drug-induced kidney diseases due to vulnerability of urinary system towards drug- induced oxidative stress (Baliga et al. 1999; Nazıroğlu et al. * Ghada M. Suddek ghmsuddek@yahoo.com 1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt Naunyn-Schmiedeberg's Arch Pharmacol DOI 10.1007/s00210-015-1164-8