Please cite this article in press as: Hegazy, A.M.S., et al., 6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats. Tissue Cell (2016), http://dx.doi.org/10.1016/j.tice.2016.03.006 ARTICLE IN PRESS G Model YTICE-993; No. of Pages 9 Tissue and Cell xxx (2016) xxx–xxx Contents lists available at ScienceDirect Tissue and Cell journal homepage: www.elsevier.com/locate/tice 6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats Ahmed M.S. Hegazy a,∗ , Mohammed M. Mosaed b , Saad H. Elshafey c , Naglaa A. Bayomy d a Anatomy Department, Benha Faculty of Medicine, Benha University, Egypt b Anatomy Department, Al-azhar Faculty of Medicine, Al-azhar University, Egypt c Histology department, Faculty of Medicine, Mansura University, Egypt d Histology Department, Faculty of Medicine, Tanta University, Tanta, Egypt a r t i c l e i n f o Article history: Received 17 September 2015 Received in revised form 13 March 2016 Accepted 14 March 2016 Available online xxx Keywords: Gentamicin Nephrotoxicity Casppase-3 HSP47 Rats a b s t r a c t Ginger or Zingiber officinale which is used in traditional medicine has been found to possess antioxidant effect that can control the generation of free radicals. Free radicals are the causes of renal cell degener- ation that leads to renal failure in case of gentamicin induced toxicity. This study was done to evaluate the possible protective effects of 6-gingerol as natural antioxidant on gentamicin-induced renal cortical oxidative stress and apoptosis in adult male albino rats. Forty adult male albino rats were used in this study and were randomly divided into four groups, control group; 6-gingerol treated group; gentamicin treated group and protected group (given simultaneous 6-gingerol and gentamicin). At the end of the study, blood samples were drawn for biochemical study. Kidney sections were processed for histological, and immunohistochemical examination for caspase-3 to detect apoptosis and anti heat shock protein 47 (HSP47) to detect oxidative damage. Gentamicin treated rats revealed a highly significant increase in renal function tests, tubular dilatation with marked vacuolar degeneration and desquamation of cells, interstitial hemorrhage and cellular infiltration. Immunohistochemically, gentamicin treated rats showed a strong positive immunoreaction for caspase-3 and anti heat shock protein 47 (HSP47). Protected rats showed more or less normal biochemical, histological, and immunohistochemical pictures. In conclusion, co-administration of 6-gingerol during gentamicin ‘therapy’ has a significant reno-protective effect in a rat model of gentamicin-induced renal damage. It is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections. © 2016 Elsevier Ltd. All rights reserved. 1. Introduction Gentamicin is an aminoglycoside that is still widely used against serious and life-threatening infections by Gram-negative aero- bic bacteria, despite that its use is limited by nephrotoxicity and ototoxicity (Hong et al., 2006; Zappitelli et al., 2011). Gen- tamicin treatment can induce acute tubular necrosis with acute renal failure in about 20% of patients with a high overall mor- tality of more than 50% (Himmelfarb, 2011). It has been stated that gentamicin is accumulated in the epithelial cells of proximal renal tubules leading to nephrotoxicity (Nagai and Takano, 2004; Padmini and Kumar, 2012). Histopathological analysis showed that administration of gentamicin caused intracellular edema, basal membrane interruption, apoptosis and acute tubular necrosis ∗ Corresponding author. E-mail address: ahmed0562301954@yahoo.com (A.M.S. Hegazy). (Souza et al., 2009). Lysis of membranous organelles as lyso- somes may release acid hydrolases which causes disruption of critical intracellular processes including mitochondrial respiration and electron transport chain (Morales et al., 2010). It has been suggested that increases in reactive oxygen species, proinflam- matory cytokines, apoptosis, decreases in glucose, and depletion of adenosine triphosphate (ATP) storage are being responsible for aminoglycoside-induced tubular, glomerular and vascular damage (Sue et al., 2009; Balakumar et al., 2010; Kim et al., 2013). Reactive oxygen species (ROS) are considered as important modulators of renal blood flow and glomerular filtration rate. Therefore, treatment with antioxidant protect the kidney from their damaging effects and acute tubular necrosis (Sue et al., 2009; Abdel-Raheem et al., 2009). There is also, a continuous search for agents which provide nephroprotection against the renal impair- ment induced by drugs like gentamicin. It is thus vitally important that we make a turn toward alternative systems of medicine for solutions. Ginger or Zingiber officinale (Z. officinale) which is used in http://dx.doi.org/10.1016/j.tice.2016.03.006 0040-8166/© 2016 Elsevier Ltd. 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