Old age and renal susceptibility to drugs. High-purity green tea ameliorates renal oxidative damage induced by gentamicin in aged rats

F Marotta1, Y Naito2, A. Lorenzetti1, A Kumari3, P Signorelli1, C Tomella1, A Polimeni1,
1ReGenera. Research Group for Aging-Intervention, Milano, Italy; 2Seyukai Medical Institute & Clinic, Nagoya, Japan; 3Department of Biology, Faculty of Science, Ankara University, Ankara, Turkey.

Up to 30% of patients treated with gentamicin (GM) for more than seven days show some signs of nephrotoxicity and this holds particularly relevant in elderly people. It has been reported that GM-induced nephrotoxicity is characterized by direct tubular necrosis, which is localized mainly in the proximal tubule. The exact mechanism of GM-induced nephrotoxicity is unknown. However, GM has been shown to enhance the generation of ROS causing increased consumption of GSH in non-enzymatic removal of oxygen-radicals. Therefore, GM may act like S-(1,2-dichlorovinyl)-L-cysteine a known nephrotoxicant and interferes with the recycling of GSSG into GSH by inhibition of the enzyme glutathione reductase. Green tea has reported to have antioxidant and free radical scavenging activities through its important catechins contents. Therefore, the aim of this work was to investigate the possible protective effect of a high-purity green extract (GTE)(Mega Green Tea Extract® containing decaffeinated leaf with 98% polyphenols and 45% epigallocathechin-gallate, LEF Ft Lauderdale, USA) against gentamicin-induced nephrotoxicity. For this purpose, 18-month old rats were divided into 4 groups. Group-1 (control) received normal saline. Group-2 received GTE (300 mg/kg/d, orally). Group-3 received gentamicin (80 mg/kg/d, intraperitoneally). Group-4 was injected with GTE plus gentamicin simultaneously. Daily urinary total protein levels were estimated to assess kidney dysfunction. The rats were sacrificed on the seventh day and kidneys were collected for histopathological studies. Blood urea nitrogen (BUN) and creatinine levels were measured in the blood. Moreover, GSH, TBARS levels, SOD and catalase activities were determined in renal tissues. GM produced elevation in urinary total protein, BUN, serum creatinine and TBARS levels. On the other hand, GM reduced the GSH level and SOD, CAT activities. GM-treated rats showed atrophy/hypertrophy of the glomeruli with degeneration and necrosis in the epithelial cells lining of renal tubules. The endothelial cells lining the glomerular tufts showed swelling and there was cytoplasmic vacuolation and focal inflammatory cells infiltration between the tubules in the corticomedullary junction and in the perivascular area of the dilated blood vessels associated with oedema. GTE reversed most of the histopathological alterations induced by GM and was found to be safe in healthy kidney. Accordingly, the administration of GTE plus GM significantly protected kidney function with normalization of all biochemical parameters (p<0.01).

Our results were consistent with the suggestion that high-quality GTE may indeed represent an effective protective agent from GM-induced kidney damage by exerting significant antioxidant and membrane lipid protective properties from oxidative/inflammatory injury.
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