The Antiproteinuric Effects of Green Tea Extract on Acute Cyclosporine-Induced Nephrotoxicity in Rats

Department of Internal Medicine, Division of Nephrology, Chosun University Hospital, Gwangju, Republic of Korea.
Transplantation Proceedings (Impact Factor: 0.98). 05/2012; 44(4):1080-2. DOI: 10.1016/j.transproceed.2012.03.047
Source: PubMed


It has been reported that the proteinuria is an early useful marker to detect cyclosporine (CsA) nephrotoxicity. The aim of this study was to investigate the antiproteinuric effects of green tea extract (GTE) on CsA-induced acute renal injury in rats.
The rats (n = 28) were divided into four groups (n = 7/group); controls intraperitoneally (IP) injected with 0.9% saline; CsA group IP injected CsA (50 mg/kg); inducible nitric oxide synthase (iNOS) inhibitor group administered in addition NG-nitro-L-arginine-methyl ester (12 mmol/L) subcutaneously and CsA-GTE group of CsA IP plus GTE (100 mg/kg) subcutaneously.
The 24-hour urine proteins were significantly increased among the CsA (22.6 ± 3.1 mg/d) compared with the control (7.1 ± 1.5 mg/d) and significantly decreased in the CsA-GTE group (8.2 ± 1.8 mg/d, P < .01). Nitric oxide production induces by CsA treatment was significantly suppressed by GTE and iNOS inhibitor. Renal tissue malondialdehyde level was significantly increased in the CsA compared with controls and significantly decreased in the CsA-GTE group. The antioxidant enzyme activities of superoxide dysmutase and catalase, which were significantly suppressed in the CsA compared with the control group, were restored in the CsA-GTE cohort.
GTE treatment of rats showed meaningful antiproteinuric effects through antioxidative activity in kidneys from CsA-induced acute renal injury.

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    • "EGCG prevents in vitro free radical-mediated hemolysis by cyclosporine (Lin et al., 2000), and induces GPX (Na and Surh, 2008; Tsai et al., 2011) SOD (Na and Surh, 2008) and GST (Na and Surh, 2008; Han et al., 2012). This evidence is also confirmed by animal studies, where both GTE (Shin et al., 2012) and EGCG (Chang and Mun, 2004) reduce cyclosporine-induced nephrotoxicity, increasing the antioxidant enzyme activities of SOD and CAT (Shin et al., 2012), and decreasing lipoperoxidation and UA (Mohamadin et al., 2005) (figure 2). However, caution should be taken in considering the use of GTE to prolong allograft survival and to reduce cyclosporine nephrotoxicity (Tripathi et al., 2009). "
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    ABSTRACT: Epigallocatechin-3-gallate (EGCG), the main flavonoid of Green Tea (GT), could play an active role in the prevention of oxidative stress related diseases, such as hematological malignancies. Some effects of EGCG are not imputable to the antioxidant activity, but involve modulation of antioxidant enzymes and uric acid (UA) levels. The latter is the major factor responsible of the plasma Non-Enzymatic Antioxidant Capacity (NEAC). However, hyperuricaemia is a frequent clinical feature caused by tumor lysis syndrome or cyclosporine side effects, before and after bone marrow transplantation (BMT). Besides, food-drug interactions could be associated with GT consumption and could have clinical implications. The molecular mechanisms involved in the redox and drug metabolizing/transporting pathways was discussed with particular reference to the potential role of GT and EGCG in BMT. Moreover, reviewing data on NEAC, isoprostanes, uric acid and various enzymes, from human studies on GT, its extract or EGCG, an increase in NEAC, no effect on isoprostanes and contrasting results on UA and enzymes were observed. Currently, few and contrasting available evidences suggest caution for GT consumption in BMT patients and more studies are needed in order to better understand the potential impact of EGCG on oxidative stress and metabolizing/transporting systems.
    No preview · Article · Jun 2015 · Critical Reviews in Food Science and Nutrition
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    • "Judging from serum creatinine levels, GTE obliterates cisplatin-induced nephrotoxicity in rats [4-6]. Moreover, GTE also exerts antiproteinuric effects on cyclosporine-induced nephrotoxicity in rats [7]. Furthermore, GTE reverses the progression of immune-mediated glomerulonephritis in mice [8]. "
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    ABSTRACT: NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with longevity in Japanese. A previous study has shown that ND2-237 Leu/Met polymorphism modulates the effects of green tea consumption on risk of hypertension. For men with ND2-237Leu, habitual green tea consumption may reduce the risk of hypertension. Moreover, there is a combined effect of ND2-237 Leu/Met polymorphism and alcohol consumption on risk of mildly decreased estimated glomerular filtration rate (eGFR) (<90 ml/min/1.73 m2). Several beneficial effects of green tea on the kidney have been reported. The objective of this study was to investigate whether ND2-237 Leu/Met polymorphism modifies the effects of green tea consumption on risk of mildly decreased eGFR in male Japanese health check-up examinees. For ND2-237Leu genotypic men, after adjustment for confounding factors, green tea consumption may increase the risk of mildly decreased eGFR (P for trend = 0.016). The adjusted odds ratio (OR) for mildly decreased eGFR was significantly higher in subjects with ND2-237Leu who consume >=6 cups of green tea per day than those who consume <=1 cup of green tea per day (adjusted OR = 5.647, 95 % confidence interval: 1.528-20.88, P = 0.009). On the other hand, for ND2-237Met genotypic men, green tea consumption does not appear to determine the risk of mildly decreased eGFR. The present results suggest that ND2-237 Leu/Met polymorphism unexpectedly modifies the effects of green tea consumption on eGFR and the risk of mildly decreased eGFR in male Japanese subjects.
    Full-text · Article · Nov 2013 · Journal of Negative Results in BioMedicine
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    ABSTRACT: There is increasing evidence suggesting that antioxidants in green tea extracts may protect kidneys on the progression of end-stage renal disease. We investigated the protective impacts of (-)-epigallocatechin 3-O-gallate (EGCG) against streptozotocin (STZ)-induced diabetic nephropathy in mice. The mice were divided into 5 groups (n=10 per group): control (saline, i.p.), STZ (200mg/kg, i.p.), EGCG50 (50mg/kg, S.Q.), EGCG100 (100mg/kg, S.Q.), and EGCG200 (200mg/kg, S.Q.). Animals were sacrificed at scheduled times after EGCG administration and then quantitative and qualitative analysis were performed. Compared with the control group, the STZ group showed an increase in levels of blood glucose, blood urea nitrogen, creatinine and urine protein amounts with a decrease in body weight. All the above parameters were significantly reversed with EGCG treatment, especially in the EGCG100 group. After STZ injection, there was a mesangial proliferation with increased renal osteopontin accumulation and its protein expression in the glomeruli and the proximal tubules. Mice kidneys after EGCG-treatment showed a reduced expression of above parameters and relatively improved histopathological findings. These results indicated that EGCG 100mg/kg might provide an effective protection against STZ-induced diabetic nephropathy in mice by osteopontin suppression.
    No preview · Article · Aug 2014 · Acta Histochemica
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