Kidney diseases are common health problems worldwide. Various etiologies (e.g., diabetes, hypertension, drug-induced nephrotoxicity, infection, cancers) can affect renal function and ultimately lead to development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). The global rise in number of CKD/ESRD patients during recent years has led to tremendous concern to look for effective strategies to prevent or slow progression of CKD and ESRD. Natural compounds derived from herbs or medicinal plants have gained wide attention for scientific scrutiny to achieve such goals. One of such natural compounds that has been extensively investigated is epigallocatechin-3-gallate (EGCG), a major polyphenol found in the tea plant (Camellia sinensis). A growing body of recent evidence has shown that EGCG may be a promising therapeutic or protective agent in various kidney diseases. This article thus highlights recent progress in medical research on beneficial effects of EGCG against a broad spectrum of kidney diseases, including acute kidney injury, cisplatin-induced nephrotoxicity, kidney stone disease, glomerulonephritis, lupus nephritis, renal cell carcinoma, diabetic nephropathy, CKD, and renal fibrosis. The renoprotective mechanisms are also detailed. Finally, future perspectives of medical research on EGCG and its potential use in clinical practice for treatment and prevention of kidney diseases are discussed.

Ethnopharmacological Relevance: Green tea, traditionally used as antidiabetic medicine, positively affects the diabetic nephropathy. It was assumed that these beneficial effects were due to the hypoglycemiant capacity of the tea, wich reduces the glycemic overload and, consequently, the advanced glycation end products rate and oxidative damage. However, these results are still controversial, since tea is not always able to exert a hypoglycemic action, as demonstrated by previous studies.

Aim: Investigate if green tea infusion can generate positive outcomes for the kidney independently of glycemic control, using a model of severe type 1 diabetes.

Material And Methods: We treated streptozotocin type 1 diabetic young rats with 100 mg/kg of green tea, daily, for 42 days, and evaluated the serum and tissue markers for stress and function. We also analyzed the ion dynamics in the organ and the morphological alterations promoted by diabetes and green tea treatment. Besides, we analyzed, by an in silico approach, the interactions of the green tea main catechins with the proteins expressed in the kidney.

Results: Our findings reveal that the components of green tea can interact with the proteins participating in cell signaling pathways that regulate energy metabolism, including glucose and glycogen synthesis, glucose reabsorption, hypoxia management, and cell death by apoptosis. Such interaction reduces glycogen accumulation in the organ, and protects the DNA. These results also reflect in a preserved glomerulus morphology, with improvement in pathological features, and suggesting a prevention of kidney function impairment.

Conclusion: Our results show that such benefits are achieved regardless of the blood glucose status, and are not dependent on the reduction of hyperglycemia.

Aims: One of the most popular beverages worldwide, green tea, was investigated for its potential protective effect in a rat model of gentamicin-induced nephrotoxicity by monitoring functional and morphological changes in kidneys.

Main Methods: The study was conducted on four groups of rats: control group (C), treated with only gentamicin (GM), treated with only green tea (GT) and treated with both gentamicin and green tea (GT+GM). Kidney function, oxidant and antioxidant parameters of renal tissue, as well as histopathological studies were assessed. Morphometric analysis was used to quantify these histopathological changes.

Key Findings: Gentamicin caused significant elevations in serum creatinine and urea and oxidative stress parameter (AOPP), while antioxidative enzyme catalase was significantly decreased. Histological sections of kidneys in GM group revealed necrosis of proximal tubules, vacuolation of cytoplasm and massive mononuclear inflammatory infiltrates in interstitium. Coadministration of green tea with gentamicin histologically showed renoprotective effect. Histological results were confirmed and quantified by morphometric analysis. Also in this group we measured ameliorated parameters of renal functions and antioxidative defense.

Significance: Regenerative potential of green tea after renal injury induced by gentamicin could be explained through the decrease of oxidative stress and lipid peroxidation. Green tea is a natural antioxidant, with many health promoting effects, widely available and in accordance to that affordable. Because of the established habits, people largely consume it as a beverage. It could be beneficial in the reduction of oxidative stress and changes caused by it primarily in renal tubules and interstitium.

Green tea (GT), through its antioxidant properties, may be useful to treat or prevent human diseases. Because several lines of evidence suggest that oxidative stress contributes to the pathogenesis of diabetic nephropathy, we tested the hypothesis that GT prevents diabetes and hypertension-related renal oxidative stress, attenuating renal injury. Spontaneously hypertensive rats (SHR) with streptozotocin-induced diabetes and nondiabetic SHR were treated daily with tap water or freshly prepared GT (13.3 g/L). After 12 wk, the systolic blood pressure did not differ between treated and untreated nondiabetic or diabetic rats. However, body weight was less (P < 0.05) and glycemia was greater in diabetic SHR rats than in nondiabetic rats. Renal oxidative stress variables such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine expression, NADPH oxidase-dependent superoxide generation, and the expression of renal cortex Nox4 were greater (P < 0.05) in diabetic rats that received water (DW) than in nondiabetic rats that received water (CW). The 8-OHdG and NADPH oxidase-dependent superoxide generation were significantly less in rats treated with GT. Nitrotyrosine and Nox4 expression were significantly less in diabetic rats that received GT (DGT) than in DW. Likewise, the indices of renal injury, albuminuria, and renal expression of collagen IV were significantly greater in DW than in CW. These differences were significantly less in DGT than in DW. GT reestablished the redox state and reduced the indicators of nephropathy without altering glycemia and blood pressure levels in diabetic SHR. These findings suggest that the consumption of GT may ameliorate nephropathy in diabetic hypertensive patients.

It has been documented that green tea (GT) and its catechin components improve renal failure and inhibit the growth of mesangial cells. In the present study we examined the long-term effect of GT extract on streptozotocin (STZ)-induced diabetic nephropathy and on the glycogen accumulation in the kidney tubules. Male Sprague-Dawley rats were randomly assigned to normal control groups (2, 6, 8 and 12 weeks) and five diabetic groups (n 10) of comparable age. A GT diabetic group received 16 % concentration of GT for 12 weeks post-diabetes induction as their sole source of drinking water. GT treatment significantly (P < 0.01) reduced the serum glucose, glycosylated protein, serum creatinine and blood urea N levels by 29.6 (sem 3.7), 22.7 (sem 5.2), 38.9 (sem 10) and 41.7 (sem 1.9) %, respectively, compared with the diabetic group of comparable age. In addition, the GT-treated group showed a significant 44 (sem 10.8) % higher creatinine clearance (Ccr) compared with the untreated diabetic group. Likewise, GT reduced the urea N, creatinine, glucose and protein excretion rates by 30 (sem 7.6), 35.4 (sem 5.3), 34.0 (sem 5.3) and 46.0 (sem 13.0) % compared with the 12 weeks diabetic group. Administration of GT to 12 weeks diabetic rats significantly (P < 0.001) prevented (99.98 (sem 0.27) % less) the accumulation of glycogen in the kidney tubules. These results indicate that in STZ diabetes, kidney function appears to be improved with GT consumption which also prevents glycogen accumulation in the renal tubules, probably by lowering blood levels of glucose. Therefore, GT could be beneficial additional therapy in the management of diabetic nephropathy.

Nicotine is a potential inducer of oxidative stress, through which it can damage numerous biological molecules. Natural antioxidants that prevent or slow the progression and severity of nicotine toxicity may have a significant health impact. The purpose of this study, conducted on Wistar rats, was to evaluate the beneficial effects of green tea () extract on nicotine treatment-induced damage on kidney. Our results showed that nicotine significantly ( < 0.01) increased serum and kidney malondialdehyde, the serum contents of urea, creatinine, and uric acid. In addition, nicotine intoxication significantly ( < 0.01) decreased the levels of vitamins E and C in serum and kidney tissue as well as the activities of superoxide dismutase, catalase, and glutathione peroxidase. Interestingly, animals that were pretreated with green tea, prior to nicotine administration, showed a significant nephroprotection, revealed by a significant reduction-induced oxidative damage for all tested markers. The nephroprotective activity of green tea is mediated, at least in part, by the antioxidant effect of its constituents.

Green tea, derived from the unoxidized leaves of Camellia sinensis (L.) Kuntze, is one of the least processed types of tea and is rich in antioxidants and polyphenols. Among these, catechins-particularly epigallocatechin gallate (EGCG)-play a key role in regulating cell signaling pathways associated with various chronic conditions, including cardiovascular diseases, neurodegenerative disorders, metabolic diseases, and cancer. This review presents a comprehensive analysis of recent clinical studies focused on the therapeutic benefits and potential risks of interventions involving green tea extracts or EGCG. A systematic literature survey identified 17 relevant studies, classified into five key areas related to catechin interventions: toxicity and detoxification, drug pharmacokinetics, cognitive functions, anti-inflammatory and antioxidant properties, and obesity and metabolism. Findings from these clinical studies suggest that the health benefits of green tea catechins outweigh the potential risks. The review highlights the importance of subject genotyping for enzymes involved in catechin metabolism to aid in interpreting liver injury biomarkers, the necessity of assessing drug-catechin interactions in clinical contexts, and the promising effects of topical EGCG in reducing inflammation. This analysis underscores the need for further research to refine therapeutic applications while ensuring the safe and effective use of green tea catechins.

Background: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2009, Issue 3).Tea is one of the most commonly consumed beverages worldwide. Teas from the plant Camellia sinensis can be grouped into green, black and oolong tea, and drinking habits vary cross-culturally. C sinensis contains polyphenols, one subgroup being catechins. Catechins are powerful antioxidants, and laboratory studies have suggested that these compounds may inhibit cancer cell proliferation. Some experimental and nonexperimental epidemiological studies have suggested that green tea may have cancer-preventative effects.

Objectives: To assess possible associations between green tea consumption and the risk of cancer incidence and mortality as primary outcomes, and safety data and quality of life as secondary outcomes.

Search Methods: We searched eligible studies up to January 2019 in CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and reference lists of previous reviews and included studies.

Selection Criteria: We included all epidemiological studies, experimental (i.e. randomised controlled trials (RCTs)) and nonexperimental (non-randomised studies, i.e. observational studies with both cohort and case-control design) that investigated the association of green tea consumption with cancer risk or quality of life, or both.

Data Collection And Analysis: Two or more review authors independently applied the study criteria, extracted data and assessed methodological quality of studies. We summarised the results according to diagnosis of cancer type.

Main Results: In this review update, we included in total 142 completed studies (11 experimental and 131 nonexperimental) and two ongoing studies. This is an additional 10 experimental and 85 nonexperimental studies from those included in the previous version of the review. Eleven experimental studies allocated a total of 1795 participants to either green tea extract or placebo, all demonstrating an overall high methodological quality based on 'Risk of bias' assessment. For incident prostate cancer, the summary risk ratio (RR) in the green tea-supplemented participants was 0.50 (95% confidence interval (CI) 0.18 to 1.36), based on three studies and involving 201 participants (low-certainty evidence). The summary RR for gynaecological cancer was 1.50 (95% CI 0.41 to 5.48; 2 studies, 1157 participants; low-certainty evidence). No evidence of effect of non-melanoma skin cancer emerged (summary RR 1.00, 95% CI 0.06 to 15.92; 1 study, 1075 participants; low-certainty evidence). In addition, adverse effects of green tea extract intake were reported, including gastrointestinal disorders, elevation of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin/subcutaneous reactions. Consumption of green tea extracts induced a slight improvement in quality of life, compared with placebo, based on three experimental studies. In nonexperimental studies, we included over 1,100,000 participants from 46 cohort studies and 85 case-control studies, which were on average of intermediate to high methodological quality based on Newcastle-Ottawa Scale 'Risk of bias' assessment. When comparing the highest intake of green tea with the lowest, we found a lower overall cancer incidence (summary RR 0.83, 95% CI 0.65 to 1.07), based on three studies, involving 52,479 participants (low-certainty evidence). Conversely, we found no association between green tea consumption and cancer-related mortality (summary RR 0.99, 95% CI 0.91 to 1.07), based on eight studies and 504,366 participants (low-certainty evidence). For most of the site-specific cancers we observed a decreased RR in the highest category of green tea consumption compared with the lowest one. After stratifying the analysis according to study design, we found strongly conflicting results for some cancer sites: oesophageal, prostate and urinary tract cancer, and leukaemia showed an increased RR in cohort studies and a decreased RR or no difference in case-control studies. AUTHORS'

Conclusions: Overall, findings from experimental and nonexperimental epidemiological studies yielded inconsistent results, thus providing limited evidence for the beneficial effect of green tea consumption on the overall risk of cancer or on specific cancer sites. Some evidence of a beneficial effect of green tea at some cancer sites emerged from the RCTs and from case-control studies, but their methodological limitations, such as the low number and size of the studies, and the inconsistencies with the results of cohort studies, limit the interpretability of the RR estimates. The studies also indicated the occurrence of several side effects associated with high intakes of green tea. In addition, the majority of included studies were carried out in Asian populations characterised by a high intake of green tea, thus limiting the generalisability of the findings to other populations. Well conducted and adequately powered RCTs would be needed to draw conclusions on the possible beneficial effects of green tea consumption on cancer risk.

Chronic kidney disease (CKD) is a major health problem worldwide. Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are highly protein-bound nephro-cardiovascular toxins, which are not efficiently removed through hemodialysis. The renal excretions of IS and PCS were mediated by organic anion transporters (OATs) such as OAT1 and OAT3. Green tea (GT) is a popular beverage containing plenty of catechins. Previous pharmacokinetic studies of teas have shown that the major molecules present in the bloodstream are the glucuronides/sulfates of tea catechins, which are putative substrates of OATs. Here we demonstrated that GT ingestion significantly elevated the systemic exposures of endogenous IS and PCS in rats with chronic renal failure (CRF). More importantly, GT also significantly increased the levels of serum creatinine (Cr) and blood urea nitrogen (BUN) in CRF rats. Mechanism studies indicated that the serum metabolites of GT (GTM) inhibited the uptake transporting functions of OAT1 and OAT3. In conclusion, GT inhibited the elimination of nephro-cardiovascular toxins such as IS and PCS, and deteriorated the renal function in CRF rats.

Green tea (Camellia sinensis) is a commonly consumed beverage or dietary supplement. As a natural product with a myriad of proposed health benefits, patients are likely to consume green tea while taking their medications unaware of its potential to interact with drugs and influence drug efficacy and safety. Catechins are the abundant polyphenolic compounds in green tea (e.g., (-)-epigallocatechin-3-gallate), which are reported to influence determinants of drug pharmacokinetics, such as drug solubility and the activity of drug transporters and drug metabolizing enzymes. This review summarized the results of clinical studies investigating the influence of green tea catechins on the pharmacokinetics of clinically used medications. The majority of analyses (72%) reported significant decreases (by 18-99%) in systemic drug exposure with green tea consumption (atorvastatin, celiprolol, digoxin, fexofenadine, folic acid, lisinopril, nadolol, nintedanib, raloxifene, and rosuvastatin). One analysis (6%) reported a 50% increase in drug systemic exposure (sildenafil) and for 22% of analyses drug pharmacokinetics were not affected by green tea consumption (fluvastatin, pseudoephedrine, simvastatin, and tamoxifen). For most drugs reporting an interaction, green tea catechins were proposed to decrease intestinal drug absorption by inhibiting OATP uptake (particularly OATP1A2), enhancing P-gp efflux activity or reducing drug solubility. Case reports have associated changes in drug pharmacokinetics with green tea consumption to changes in drug efficacy or safety (e.g., nadolol and erlotinib). These findings prompt the need for further research in relating evidence from existing literature to predict additional clinically important green tea-drug interactions and to provide appropriate recommendations for patients and clinicians.