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Beneficial Effects of Green Tea Extract in Gentamicin-Induced Acute Renal Failure in Rats / Povoljni efekti ekstrakta zelenog čaja na akutnu bubrežnu insuficijenciju uzrokovanu gentamicinom kod pacova

Beneficial Effects of Green Tea Extract in Gentamicin-Induced Acute Renal Failure in Rats /... ACTA FACULTATIS MEDICAE NAISSENSIS DOI: 10.1515/afmnai-2015-0005 UDC: 633.72:[615.33:616.61-008.6 Beneficial Effects of Green Tea Extract in Gentamicin-Induced Acute Renal Failure in Rats Milica Veljkovi1, Sonja Ili1, Nenad Stojiljkovi1, Ljubinka Velickovi2, Dragana Pavlovi3, Mirjana Radenkovi1, Suzana Brankovi1, Dusanka Kiti3, Marija Gocmanac Ignjatovi1 University of Nis, Faculty of Medicine, Institute of Physiology, Serbia University of Nis, Faculty of Medicine, Institute of Pathology, Serbia University of Nis, Faculty of Medicine, Department of Pharmacognosy, Serbia SUMMARY The aim of this study was to investigate whether green tea extract has beneficial effect on gentamicin-induced acute renal failure. The investigation was conducted on thirty-two Wistar rats divided into four groups of 8 animals each. Control (C) group received normal saline. GT group received green tea extract orally, 300mg/kg. GM group received gentamicin intraperitoneally, 100mg/kg and GT+GM group received both gentamicin and green tea extract. Histological sections of kidney in GM group revealed necrosis of proximal tubules, vacuolization of cytoplasm and massive mononuclear inflammatory infiltrates in interstitium. Coadministration of green tea with gentamicin had renoprotective effect and showed only mild infiltrations, normal glomeruli and alleviated tubular degeneration. Analysis of biochemical parameters showed significantly higher urea and creatinine serum concentrations in GM group in comparison with C group and GT+GM group (p<0.001). Plasma lipid peroxidation biomarker MDA was significantly higher in GM group than those in C group (p<0.001), whereas the values for GT+GM group were significantly lower than MDA recorded for GM group (p<0.001). Beneficial effects of green tea on gentamicin-induced nephrotoxicity is explained through decrease of oxidative stress and lipid peroxidation.Our results indicate that green tea administration has nephroprotective effect on oxidative stress and acute renal failure caused by gentamicin. Key words: gentamicin, green tea, extract, rats Corresponding author: Milica Veiljkovi phone: +381641939374 e-mail: milica.veljkovic@gmail.com INTRODUCTION Gentamicin is a widely used aminoglycoside antibiotic with a low price and high effectivity in treatment of gram-negative and -lactam resistent infections (1). However, its use has been limited because of its adverse effect of causing nephrotoxicity (2). Gentamicin-induced nephrotoxicity is an animal model for study of acute kidney failure in experimental research (3). Although the mechanism by which gentamicin causes nephrotoxicity remains unclear, proposed pathological mechanisms include induction of oxidative stress, apoptosis, necrosis, elevation of endothelin I and increase of monocyte/macrophages infiltration (3­5). Getamicininduced nephrotoxicity is clinically characterized by increased serum creatinine and blood urea nitrogen and decreased glomerular filtration rate (2,3) and morphologically by focal necrosis and apoptosis in tubular epithelium with extensive peritubular cell inflammation (2). Gentamicin increases generation of reactive oxygen species (ROS), such as super oxide anions (6), hydroxyl radicals, hydrogen peroxide and reactive nitrogen species in the kidney (3). Most research studies on gentamicin-induced nephrotoxicity are focused on the use of various antioxidants (3). Green tea (Camellia Sinensis) contains the highest concentration of powerful antioxidants called polyphenols also known as green tea catechins (7). The important catechins contents of green tea are epicatechin, epicatechin-3-gallate, epigallocatechin and epigallocatechin-3-gallate (7,8). These polyphenols in green tea can neutralize free radicals and may reduce some of the damage caused by reactive oxygen species (ROS) (7). In this study, we aimed to evaluate green tea extract (GTE) as an inhibitory agent against gentamicin-induced acute renal failure because of its antioxidant property. sample from "Josif Pancic", Pancevo, Serbia) were obtained after evaporation to the dryness in vacuo under 40ºC and extraction yield was 25%. Chemicals, reagents and solvents used in the experiment were of analytical grade. Animals Thirty-two Wistar albino rats, weighing 200 ­ 250g, were selected for this study. The control group of rats (C group) received 1 ml saline solution per day intraperitoneally for 8 days. The green tea (GT) group received an oral administration of 300 mg/kg/day of green tea for 15 days using an intragastric enteral feeding protocol (1). The gentamicin (GM) group was injected subcutaneously with gentamicin (Actavis company, Leskovac, Serbia) 100 mg/kg/day for the last 8 days of experiment. The green tea and gentamicin group (GT+GM) group was treated orally with green tea 300 mg/kg/day for 15 days concomitantly with intraperitoneal injection of gentamicin, in the same dose like GM group, for the last 8 days of experiment. Fifteen days after the beginning of the experiment all animals were anaesthetized using 80 mg/kg ketamine (Ketamidor 10%, Richter Pharma AG, Wels, Austria) and sacrificed. Blood samples for biochemical analysis were taken from the aorta (2ml). The kidney was subsequently removed and cut into two pieces for biochemical analysis and light microscopy. All experimental procedures were conducted in accordance with the principles for the care and use of laboratory animals for scientific purposes contained in the European Union regulations and USA Guide for the Care and Use of Laboratory Animals. Histological analysis After the kidneys were dissected, tissues were fixed in 10% paraformaldehyde (2), dehydrated in ascending graded series of alcohol and embedded in paraffin. Kidney tissues were cut into pieces of 5 m thickness using a HistoRange microtome (model: LKB 2218, LKB-Produkter AB, Bromma, Sweden) followed by staining with hematoxylin and eosin (HE) according to conventional staining protocols. The histological sections were examined under a light microscope Leica DMR (Leica Microsystems AG, Wetzlar, Germany) M A T E R I A L S A ND M E T H O D S Preparation of Ethanolic Green Tea extract (GTE) Green tea leaves were reduced to a fine powder with ethanol (70% v/v) by percolation, as described in European Pharmacopeia 6.0 (Ph. Eur. 5, 2007). The ethanolic extract of Camellia Sinensis (commercial Biochemical analysis Blood samples taken from the aorta were analyzed for markers of renal failure. Urea and creatinine concentrations in serum were measured using an automatic biochemical analyzer (A25 Biosystems, Barcelona, Spain) in the laboratory of the Clinic of Nephrology Clinical Center Nis. Statistical analysis All values are expressed as mean ± SD. All data were compared between groups by one-way analysis of variance (ANOVA) followed by Tukey's post hoc test for multiple comparison (Graphpad Prism version 5.03, San Diego, CA, USA). The value less than 0.05 was considered significant. Estimation of lipid peroxidation Serum malondialdehyde as a marker of lipid peroxidation was assessed by thiobarbitoric acid test, (3) spectrophotometrically. Homogenate absorption was measured at 532 nm. The malondialdehyde / lipid peroxidation end-product concentration was expressed per mg/protein using the molecular extinction coefficient of MDA (1.56 × 10-5 mol cm-1). RESULTS Histological analysis Sections from control (C) group (Figure 1) shows normal histological structure of the glomeruli and renal tubules (7). In GM group (Figure 2) renal sections showed glomerular congestion, narrowed Bowman`s space, periglomerular inflammation and hyaline cylinders. Proximal tubules were undergoing necrosis, vacuolization of cytoplasm and epithelial desquamation. Interstitium showed massive mononuclear inflammatory infiltrates. Figure 1: Histopathological view of renal sections of C group of rats (HE x 200) Figure 2. Histopathological view of renal sections of GM group of rats (HE x 200) Green tea (Figure 3) reversed most of the histopathological alterations induced by gentamicin as seen from sections from GT+GM group (7). Figure 4 shows normal glomeruli, alleviated tubular degeneration and mild to moderate mononuclear inflammatory infiltrates. The rest of histopathological changes produced by gentamicin were completely prevented by green tea treatment. There were no necrosis of the epithelial cells of proximal tubules and no hyaline cylinders. Green tea alone (GT group) was found to be safe and did not induce any histopathological changes in the kidney. Figure 3. Histopathological view of renal sections of GT group of rats (HE x 200) Figure 4. Histopathological view of renal sections of GT+GM group of rats (HE x 200) Biochemical analysis In the GM group when compared to the C group, the analysis of biochemical parameters showed a significant increase of urea and creatinine serum concentrations (p <0.001) (Table 1). In the GT+GM group, creatinine concentrations were elevated compared to the control group but not statistically, but these values were significantly decreased compared to the GM group (p<0.001). Levels of urea were not significantly elevated in GT+GM group in comparison with the C group and were significantly lower when compared to the GM group of animals (p<0.001). Table 1. Biochemical analysis of rat serum creatinine and urea concentrations SERUM CONCENTRATION C group 5.44 ± 0.7127 38.38 ± 1.931 GM group 268.4 ± 55.39*** 158.6 ± 37.92*** GT group 46.31 ± 7.665### 51.84 ± 5.607### GT+GM group 86.14 ± 20.57### 51.94 ± 2.27### CREATININE (µmol/L) UREA (mmol/L) ### p< 0.001 VS. GM ***p< 0.001 VS. C Estimation of lipid peroxidation Gentamicin administration to rats significantly increased the MDA levels in the kidney tissue compared to C group (p<0.001). Coadministration of green tea in the GT+GM group reduced lipid peroxidation, as evidenced by significantly decreased level of MDA when compared to the GM group (p<0.001) (Figure 5). Our results showed decrease in serum creatinine and urea in group that was simultaneously treated with green tea, which indicates that administration of green tea ameliorates glomerular function (3). The biochemical analysis of our study was confirmed by the histopathological analysis, where GM group show necrosis of proximal tubules, vacuolization of cytoplasm and massive mononuclear inflammatory infiltrates in interstitium. Coadministration of green tea with gentamicin had renoprotective effect and showed only mild infiltrations, normal glomeruli and alleviated tubular degeneration (1). The renoprotective effect of green tea extract has been previously reported by Salem EA et al (1) and Khan et al (10). Tea, the most consumed beverage since ancient times, is known for its beneficial health effects. Green tea polyphenols, mainly catechins and their derivatives have been shown to have antimutagenic, anticarcinogenic, neuroprotective, antidiabetic and antibacterial health benefit. Their most important property, when it comes to our study, is their antioxidant action (10). These polyphenols include epicatechin, epicatechin-3-gallate, epigallocatechin and epigallocatechin-3-gallate, with the latter being the main polyphenol in green tea, acting protective against renal injury. It is suggested that epigallocatechin-3-gallate participates in the elimination of uremic toxins and prevention of renal failure. Also, green tea polyphenols inhibit synthesis of vasoconstrictor generation, such as thromboxane A2 and prostaglandine D2 (1) and inhibit inflammatory responses by attenuating NF kappa B activation. *** ### ### µmol/mg T T+ G M G G M C ### p< 0.001 VS. GM ***p< 0.001 VS. C Figure 5. Values of kidney malondialdehyde in separate groups of treated rats DISCUSSION Gentamicin is still considered to be an important antibiotic against life-threatening infections despite its nephrotoxic effect (7). Moreover, gentamicin-induced nephrotoxicity has been widely used as an animal model to study acute kidney failure in experimental research (3). It is suggested that the most important factor in pathogenesis of gentamicininduced nephrotoxicity is oxidative stress and generation of reactive oxygen species (ROS). ROS induces tubular necrosis, decrease of glomerular filtration rate and inflammation by activating nuclear factor kappa B (3). We found that gentamicin caused marked elevations of serum creatinine and urea concentrations (p <0.001) compared with control group. Increased level of malondialdehyde (p<0.001) compared to control group indicates free radicals generation in gentamicin-induced nephrotoxicity. Increase of serum creatinine, urea and malondialdehyde were inhibited significantly in rats simultaneously treated with green tea and gentamicin compared to gentamicin-only treated rats. The majority of previous experiments studying protections against gentamicin-induced nephrotoxicity were focused on the use of different antioxidant substances, including the extracts from medicinal plants with antioxidant properties. However, none of these have been found to be safe/suitable for clinical practice (9). CONCLUSION Our study showed that green tea reduces gentamicin-induced functional and histological kidney damage. These results may indicate that green tea is beneficial as a protective agent in gentamicininduced nephrotoxicity, possibly by inhibition of lipid peroxidation and enhancing antioxidant activity. Declaration of interest The authors report no conflicts of interes. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Acta Facultatis Medicae Naissensis de Gruyter

Beneficial Effects of Green Tea Extract in Gentamicin-Induced Acute Renal Failure in Rats / Povoljni efekti ekstrakta zelenog čaja na akutnu bubrežnu insuficijenciju uzrokovanu gentamicinom kod pacova

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Abstract

ACTA FACULTATIS MEDICAE NAISSENSIS DOI: 10.1515/afmnai-2015-0005 UDC: 633.72:[615.33:616.61-008.6 Beneficial Effects of Green Tea Extract in Gentamicin-Induced Acute Renal Failure in Rats Milica Veljkovi1, Sonja Ili1, Nenad Stojiljkovi1, Ljubinka Velickovi2, Dragana Pavlovi3, Mirjana Radenkovi1, Suzana Brankovi1, Dusanka Kiti3, Marija Gocmanac Ignjatovi1 University of Nis, Faculty of Medicine, Institute of Physiology, Serbia University of Nis, Faculty of Medicine, Institute of Pathology, Serbia University of Nis, Faculty of Medicine, Department of Pharmacognosy, Serbia SUMMARY The aim of this study was to investigate whether green tea extract has beneficial effect on gentamicin-induced acute renal failure. The investigation was conducted on thirty-two Wistar rats divided into four groups of 8 animals each. Control (C) group received normal saline. GT group received green tea extract orally, 300mg/kg. GM group received gentamicin intraperitoneally, 100mg/kg and GT+GM group received both gentamicin and green tea extract. Histological sections of kidney in GM group revealed necrosis of proximal tubules, vacuolization of cytoplasm and massive mononuclear inflammatory infiltrates in interstitium. Coadministration of green tea with gentamicin had renoprotective effect and showed only mild infiltrations, normal glomeruli and alleviated tubular degeneration. Analysis of biochemical parameters showed significantly higher urea and creatinine serum concentrations in GM group in comparison with C group and GT+GM group (p<0.001). Plasma lipid peroxidation biomarker MDA was significantly higher in GM group than those in C group (p<0.001), whereas the values for GT+GM group were significantly lower than MDA recorded for GM group (p<0.001). Beneficial effects of green tea on gentamicin-induced nephrotoxicity is explained through decrease of oxidative stress and lipid peroxidation.Our results indicate that green tea administration has nephroprotective effect on oxidative stress and acute renal failure caused by gentamicin. Key words: gentamicin, green tea, extract, rats Corresponding author: Milica Veiljkovi phone: +381641939374 e-mail: milica.veljkovic@gmail.com INTRODUCTION Gentamicin is a widely used aminoglycoside antibiotic with a low price and high effectivity in treatment of gram-negative and -lactam resistent infections (1). However, its use has been limited because of its adverse effect of causing nephrotoxicity (2). Gentamicin-induced nephrotoxicity is an animal model for study of acute kidney failure in experimental research (3). Although the mechanism by which gentamicin causes nephrotoxicity remains unclear, proposed pathological mechanisms include induction of oxidative stress, apoptosis, necrosis, elevation of endothelin I and increase of monocyte/macrophages infiltration (3­5). Getamicininduced nephrotoxicity is clinically characterized by increased serum creatinine and blood urea nitrogen and decreased glomerular filtration rate (2,3) and morphologically by focal necrosis and apoptosis in tubular epithelium with extensive peritubular cell inflammation (2). Gentamicin increases generation of reactive oxygen species (ROS), such as super oxide anions (6), hydroxyl radicals, hydrogen peroxide and reactive nitrogen species in the kidney (3). Most research studies on gentamicin-induced nephrotoxicity are focused on the use of various antioxidants (3). Green tea (Camellia Sinensis) contains the highest concentration of powerful antioxidants called polyphenols also known as green tea catechins (7). The important catechins contents of green tea are epicatechin, epicatechin-3-gallate, epigallocatechin and epigallocatechin-3-gallate (7,8). These polyphenols in green tea can neutralize free radicals and may reduce some of the damage caused by reactive oxygen species (ROS) (7). In this study, we aimed to evaluate green tea extract (GTE) as an inhibitory agent against gentamicin-induced acute renal failure because of its antioxidant property. sample from "Josif Pancic", Pancevo, Serbia) were obtained after evaporation to the dryness in vacuo under 40ºC and extraction yield was 25%. Chemicals, reagents and solvents used in the experiment were of analytical grade. Animals Thirty-two Wistar albino rats, weighing 200 ­ 250g, were selected for this study. The control group of rats (C group) received 1 ml saline solution per day intraperitoneally for 8 days. The green tea (GT) group received an oral administration of 300 mg/kg/day of green tea for 15 days using an intragastric enteral feeding protocol (1). The gentamicin (GM) group was injected subcutaneously with gentamicin (Actavis company, Leskovac, Serbia) 100 mg/kg/day for the last 8 days of experiment. The green tea and gentamicin group (GT+GM) group was treated orally with green tea 300 mg/kg/day for 15 days concomitantly with intraperitoneal injection of gentamicin, in the same dose like GM group, for the last 8 days of experiment. Fifteen days after the beginning of the experiment all animals were anaesthetized using 80 mg/kg ketamine (Ketamidor 10%, Richter Pharma AG, Wels, Austria) and sacrificed. Blood samples for biochemical analysis were taken from the aorta (2ml). The kidney was subsequently removed and cut into two pieces for biochemical analysis and light microscopy. All experimental procedures were conducted in accordance with the principles for the care and use of laboratory animals for scientific purposes contained in the European Union regulations and USA Guide for the Care and Use of Laboratory Animals. Histological analysis After the kidneys were dissected, tissues were fixed in 10% paraformaldehyde (2), dehydrated in ascending graded series of alcohol and embedded in paraffin. Kidney tissues were cut into pieces of 5 m thickness using a HistoRange microtome (model: LKB 2218, LKB-Produkter AB, Bromma, Sweden) followed by staining with hematoxylin and eosin (HE) according to conventional staining protocols. The histological sections were examined under a light microscope Leica DMR (Leica Microsystems AG, Wetzlar, Germany) M A T E R I A L S A ND M E T H O D S Preparation of Ethanolic Green Tea extract (GTE) Green tea leaves were reduced to a fine powder with ethanol (70% v/v) by percolation, as described in European Pharmacopeia 6.0 (Ph. Eur. 5, 2007). The ethanolic extract of Camellia Sinensis (commercial Biochemical analysis Blood samples taken from the aorta were analyzed for markers of renal failure. Urea and creatinine concentrations in serum were measured using an automatic biochemical analyzer (A25 Biosystems, Barcelona, Spain) in the laboratory of the Clinic of Nephrology Clinical Center Nis. Statistical analysis All values are expressed as mean ± SD. All data were compared between groups by one-way analysis of variance (ANOVA) followed by Tukey's post hoc test for multiple comparison (Graphpad Prism version 5.03, San Diego, CA, USA). The value less than 0.05 was considered significant. Estimation of lipid peroxidation Serum malondialdehyde as a marker of lipid peroxidation was assessed by thiobarbitoric acid test, (3) spectrophotometrically. Homogenate absorption was measured at 532 nm. The malondialdehyde / lipid peroxidation end-product concentration was expressed per mg/protein using the molecular extinction coefficient of MDA (1.56 × 10-5 mol cm-1). RESULTS Histological analysis Sections from control (C) group (Figure 1) shows normal histological structure of the glomeruli and renal tubules (7). In GM group (Figure 2) renal sections showed glomerular congestion, narrowed Bowman`s space, periglomerular inflammation and hyaline cylinders. Proximal tubules were undergoing necrosis, vacuolization of cytoplasm and epithelial desquamation. Interstitium showed massive mononuclear inflammatory infiltrates. Figure 1: Histopathological view of renal sections of C group of rats (HE x 200) Figure 2. Histopathological view of renal sections of GM group of rats (HE x 200) Green tea (Figure 3) reversed most of the histopathological alterations induced by gentamicin as seen from sections from GT+GM group (7). Figure 4 shows normal glomeruli, alleviated tubular degeneration and mild to moderate mononuclear inflammatory infiltrates. The rest of histopathological changes produced by gentamicin were completely prevented by green tea treatment. There were no necrosis of the epithelial cells of proximal tubules and no hyaline cylinders. Green tea alone (GT group) was found to be safe and did not induce any histopathological changes in the kidney. Figure 3. Histopathological view of renal sections of GT group of rats (HE x 200) Figure 4. Histopathological view of renal sections of GT+GM group of rats (HE x 200) Biochemical analysis In the GM group when compared to the C group, the analysis of biochemical parameters showed a significant increase of urea and creatinine serum concentrations (p <0.001) (Table 1). In the GT+GM group, creatinine concentrations were elevated compared to the control group but not statistically, but these values were significantly decreased compared to the GM group (p<0.001). Levels of urea were not significantly elevated in GT+GM group in comparison with the C group and were significantly lower when compared to the GM group of animals (p<0.001). Table 1. Biochemical analysis of rat serum creatinine and urea concentrations SERUM CONCENTRATION C group 5.44 ± 0.7127 38.38 ± 1.931 GM group 268.4 ± 55.39*** 158.6 ± 37.92*** GT group 46.31 ± 7.665### 51.84 ± 5.607### GT+GM group 86.14 ± 20.57### 51.94 ± 2.27### CREATININE (µmol/L) UREA (mmol/L) ### p< 0.001 VS. GM ***p< 0.001 VS. C Estimation of lipid peroxidation Gentamicin administration to rats significantly increased the MDA levels in the kidney tissue compared to C group (p<0.001). Coadministration of green tea in the GT+GM group reduced lipid peroxidation, as evidenced by significantly decreased level of MDA when compared to the GM group (p<0.001) (Figure 5). Our results showed decrease in serum creatinine and urea in group that was simultaneously treated with green tea, which indicates that administration of green tea ameliorates glomerular function (3). The biochemical analysis of our study was confirmed by the histopathological analysis, where GM group show necrosis of proximal tubules, vacuolization of cytoplasm and massive mononuclear inflammatory infiltrates in interstitium. Coadministration of green tea with gentamicin had renoprotective effect and showed only mild infiltrations, normal glomeruli and alleviated tubular degeneration (1). The renoprotective effect of green tea extract has been previously reported by Salem EA et al (1) and Khan et al (10). Tea, the most consumed beverage since ancient times, is known for its beneficial health effects. Green tea polyphenols, mainly catechins and their derivatives have been shown to have antimutagenic, anticarcinogenic, neuroprotective, antidiabetic and antibacterial health benefit. Their most important property, when it comes to our study, is their antioxidant action (10). These polyphenols include epicatechin, epicatechin-3-gallate, epigallocatechin and epigallocatechin-3-gallate, with the latter being the main polyphenol in green tea, acting protective against renal injury. It is suggested that epigallocatechin-3-gallate participates in the elimination of uremic toxins and prevention of renal failure. Also, green tea polyphenols inhibit synthesis of vasoconstrictor generation, such as thromboxane A2 and prostaglandine D2 (1) and inhibit inflammatory responses by attenuating NF kappa B activation. *** ### ### µmol/mg T T+ G M G G M C ### p< 0.001 VS. GM ***p< 0.001 VS. C Figure 5. Values of kidney malondialdehyde in separate groups of treated rats DISCUSSION Gentamicin is still considered to be an important antibiotic against life-threatening infections despite its nephrotoxic effect (7). Moreover, gentamicin-induced nephrotoxicity has been widely used as an animal model to study acute kidney failure in experimental research (3). It is suggested that the most important factor in pathogenesis of gentamicininduced nephrotoxicity is oxidative stress and generation of reactive oxygen species (ROS). ROS induces tubular necrosis, decrease of glomerular filtration rate and inflammation by activating nuclear factor kappa B (3). We found that gentamicin caused marked elevations of serum creatinine and urea concentrations (p <0.001) compared with control group. Increased level of malondialdehyde (p<0.001) compared to control group indicates free radicals generation in gentamicin-induced nephrotoxicity. Increase of serum creatinine, urea and malondialdehyde were inhibited significantly in rats simultaneously treated with green tea and gentamicin compared to gentamicin-only treated rats. The majority of previous experiments studying protections against gentamicin-induced nephrotoxicity were focused on the use of different antioxidant substances, including the extracts from medicinal plants with antioxidant properties. However, none of these have been found to be safe/suitable for clinical practice (9). CONCLUSION Our study showed that green tea reduces gentamicin-induced functional and histological kidney damage. These results may indicate that green tea is beneficial as a protective agent in gentamicininduced nephrotoxicity, possibly by inhibition of lipid peroxidation and enhancing antioxidant activity. Declaration of interest The authors report no conflicts of interes.

Journal

Acta Facultatis Medicae Naissensisde Gruyter

Published: Mar 1, 2015

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