Diabetic nephropathy; diabetic kidney disease; green tea; recent-onset diabetes; type 1 diabetes
Abstract :
[en] 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.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Maia Ladeira, Luiz Carlos ; Université de Liège - ULiège > GIGA > GIGA In silico medecine - Biomechanics Research Unit
dos Santos, Eliziária Cardoso
Santos, Talita Amorim
da Silva, Janaina
Lima, Graziela Domingues de Almeida
Machado-Neves, Mariana
da Silva, Renê Chagas
Freitas, Mariella Bontempo
Maldonado, Izabel Regina dos Santos Costa
Language :
English
Title :
Green tea infusion prevents diabetic nephropathy aggravation in recent-onset type 1 diabetes regardless of glycemic control
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Bibliography
Aebi, H., [13] Catalase in vitro. Methods in Enzymology, Methods in Enzymology, 1984, Elsevier, 121–126, 10.1016/S0076-6879(84)05016-3.
Al-Numair, K.S., Veeramani, C., Alsaif, M.A., Chandramohan, G., Influence of kaempferol, a flavonoid compound, on membrane-bound ATPases in streptozotocin-induced diabetic rats. Pharm. Biol. 53 (2015), 1372–1378, 10.3109/13880209.2014.982301.
Arataki, M., On the postnatal growth of the kidney, with special reference to the number and size of the glomeruli (albino rat). Am. J. Anat. 36 (1926), 399–436, 10.1002/aja.1000360302.
Bader, G.D., Hogue, C.W.V., An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinf. 4 (2003), 1–27, 10.1186/1471-2105-4-2.
Barkaoui, M., Katiri, A., Boubaker, H., Msanda, F., Ethnobotanical survey of medicinal plants used in the traditional treatment of diabetes in Chtouka Ait Baha and Tiznit (Western Anti-Atlas), Morocco. J. Ethnopharmacol. 198 (2017), 338–350, 10.1016/j.jep.2017.01.023.
Bernas, T., Asem, E.K., Robinson, J.P., Cook, P.R., Dobrucki, J.W., Confocal fluorescence imaging of photosensitised DNA denaturation in cell nuclei. Photochem. Photobiol. 33342 (2005), 960–969, 10.1562/2004-11-11-ra-369.
Bindea, G., Galon, J., Mlecnik, B., CluePedia Cytoscape plugin: pathway insights using integrated experimental and in silico data. Bioinformatics 29 (2013), 661–663, 10.1093/bioinformatics/btt019.
Bindea, G., Mlecnik, B., Hackl, H., Charoentong, P., Tosolini, M., Kirilovsky, A., Fridman, W.H., Pagès, F., Trajanoski, Z., Galon, J., ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25 (2009), 1091–1093, 10.1093/bioinformatics/btp101.
Borges, C.M., Papadimitriou, A., Duarte, D.A., Lopes De Faria, J.M., Lopes De Faria, J.B., The use of green tea polyphenols for treating residual albuminuria in diabetic nephropathy: a double-blind randomised clinical trial. Sci. Rep. 6 (2016), 1–9, 10.1038/srep28282.
Chopade, V.V., Phatak, A.A., Upaganlawar, A.B., Tankar, A.A., Green tea (Camellia sinensis): chemistry, traditional, medicinal uses and its pharmacological activities- a review. Phcog. Rev. 2 (2008), 157–162.
Collins, Q.F., Liu, H.-Y.Y., Pi, J., Liu, Z., Quon, M.J., Cao, W., Epigallocatechin-3-gallate (EGCG), A green tea polyphenol, suppresses hepatic gluconeogenesis through 5′-AMP-activated protein kinase. J. Biol. Chem. 282 (2007), 30143–30149, 10.1074/jbc.M702390200.
da Silva, E., Natali, A.J., da Silva, M.F., de Jesus Gomes, G., da Cunha, D.N.Q., Toledo, M.M., Drummond, F.R., Ramos, R.M.S., dos Santos, E.C., Novaes, R.D., de Oliveira, L.L., Maldonado, I.R., dos, S.C., Swimming training attenuates the morphological reorganization of the myocardium and local inflammation in the left ventricle of growing rats with untreated experimental diabetes. Pathol. Res. Pract. 212 (2016), 325–334, 10.1016/j.prp.2016.02.005.
de Godoi, R.S., Almerão, M.P., da Silva, F.R., In silico evaluation of the antidiabetic activity of natural compounds from Hovenia dulcis Thunberg. J. Herb. Med., 2020, 100349, 10.1016/j.hermed.2020.100349.
Dias, F.C.R., Martins, A.L.P., de Melo, F.C.S.A., Cupertino, M. do C., Gomes, M. de L.M., de Oliveira, J.M., Damasceno, E.M., Silva, J., Otoni, W.C., da Matta, S.L.P., Hydroalcoholic extract of Pfaffia glomerata alters the organization of the seminiferous tubules by modulating the oxidative state and the microstructural reorganization of the mice testes. J. Ethnopharmacol. 233 (2019), 179–189, 10.1016/j.jep.2018.12.047.
Dieterich, S., Bieligk, U., Beulich, K., Hasenfuss, G., Prestle, J., Gene expression of antioxidative enzymes in the human Heart: increased expression of catalase in the end-stage failing heart. Circulation 101 (2000), 33–39, 10.1161/01.CIR.101.1.33.
Eid, A., Bodin, S., Ferrier, B., Delage, H., Boghossian, M., Martin, M., Baverel, G., Conjard, A., Intrinsic gluconeogenesis is enhanced in renal proximal tubules of Zucker diabetic fatty rats. J. Am. Soc. Nephrol. 17 (2006), 398–405, 10.1681/ASN.2005070742.
Fallah Huseini, H., Fakhrzadeh, H., Larijani, B., Shikh Samani, A.H., Review of anti-diabetic medicinal plant used in traditional medicine. J. Med. Plants 5 (2006), 1–8.
Feng, Q., Liu, D., Lu, Y., Liu, Z., The interplay of renin-angiotensin system and toll-like receptor 4 in the inflammation of diabetic nephropathy. J. Immunol. Res. 2020 (2020), 1–11, 10.1155/2020/6193407.
Fiske, C.C.H., Subbarow, Y.Y., The colorimetric determination of phosphorus. J. Biol. Chem. 66 (1925), 375–400.
Gilbert, R.E., Proximal tubulopathy: prime mover and key therapeutic target in diabetic kidney disease. Diabetes 66 (2017), 791–800, 10.2337/db16-0796.
Habig, W.H., Pabst, M.J., Jakoby, W.B., Glutathione S-Transferases: the first enzymatic step in mercapturic acid formation. J. Biol. Chem. 25 (1974), 7130–7139.
Haraguchi, R., Kohara, Y., Matsubayashi, K., Kitazawa, R., Kitazawa, S., New insights into the pathogenesis of diabetic nephropathy: proximal renal tubules are primary target of oxidative stress in diabetic kidney. Acta Histochem. Cytoc. 53 (2020), 21–31, 10.1267/ahc.20008.
Hayashi, D., Ueda, S., Yamanoue, M., Saito, N., Ashida, H., Shirai, Y., Epigallocatechin-3-gallate activates diacylglycerol kinase alpha via a 67 kDa laminin receptor: a possibility of galloylated catechins as functional food to prevent and/or improve diabetic renal dysfunctions. J. Funct. Foods 15 (2015), 561–569, 10.1016/j.jff.2015.04.005.
Hayashi, D., Wang, L., Ueda, S., Yamanoue, M., Ashida, H., Shirai, Y., The mechanisms of ameliorating effect of a green tea polyphenol on diabetic nephropathy based on diacylglycerol kinase α. Sci. Rep. 10 (2020), 1–12, 10.1038/s41598-020-68716-6.
Herman-Edelstein, M., Doi, S.Q., Pathophysiology of Diabetic Nephropathy, Proteinuria: Basic Mechanisms, Pathophysiology and Clinical Relevance. 2016, Elsevier Inc, 10.1007/978-3-319-43359-2_4.
Itagaki, S. ichi, Nishida, E., Lee, M.J., Doi, K., Histopathology of subacute renal lesions in mice induced by streptozotocin. Exp. Toxicol. Pathol. 47 (1995), 485–491, 10.1016/S0940-2993(11)80332-5.
Itoh, Y., Yasui, T., Okada, A., Tozawa, K., Hayashi, Y., Kohri, K., Examination of the anti-oxidative effect in renal tubular cells and apoptosis by oxidative stress. Urol. Res. 33 (2005), 261–266, 10.1007/s00240-005-0465-7.
Jassal, B., Matthews, L., Viteri, G., Gong, C., Lorente, P., Fabregat, A., Sidiropoulos, K., Cook, J., Gillespie, M., Haw, R., Loney, F., May, B., Milacic, M., Rothfels, K., Sevilla, C., Shamovsky, V., Shorser, S., Varusai, T., Weiser, J., Wu, G., Stein, L., Hermjakob, H., D'Eustachio, P., The reactome pathway knowledgebase. Nucleic Acids Res. 48 (2020), D498–D503, 10.1093/nar/gkz1031.
Kang, J., Dai, X.-S., Yu, T.-B., Wen, B., Yang, Z.-W., Glycogen accumulation in renal tubules, a key morphological change in the diabetic rat kidney. Acta Diabetol. 42 (2005), 110–116, 10.1007/s00592-005-0188-9.
Kim-Park, W.K., Allam, E.S., Palasuk, J., Kowolik, M., Park, K.K., Windsor, L.J., Green tea catechin inhibits the activity and neutrophil release of Matrix Metalloproteinase-9. J. Tradit. Complement. Med. 6 (2016), 343–346, 10.1016/j.jtcme.2015.02.002.
Kobayashi, Y., Suzuki, M., Satsu, H., Arai, S., Hara, Y., Suzuki, K., Miyamoto, Y., Shimizu, M., Green tea polyphenols inhibit the sodium-dependent glucose transporter of intestinal epithelial cells by a competitive mechanism. J. Agric. Food Chem. 48 (2000), 5618–5623, 10.1021/jf0006832.
Kumazoe, M., Fujimura, Y., Tachibana, H., 67-kDa laminin receptor mediates the beneficial effects of green tea polyphenol EGCG. Curr. Pharmacol. Rep., 2020, 10.1007/s40495-020-00228-3.
Ladeira, L.C.M., dos Santos, E.C., Mendes, B.F., Gutierrez, E.A., Santos, C.F.F., de Souza, F.B., Machado-Neves, M., Maldonado, I.R., dos, S.C., Green tea infusion aggravates nutritional status of the juvenile untreated STZ-induced type 1 diabetic rat. bioRxiv, 35, 2020, 10.1101/2020.01.13.904896.
Ladeira, L.C.M., dos Santos, E.C., Valente, G.E., da Silva, J., Santos, T.A., dos Santos Costa Maldonado, I.R., Could biological tissue preservation methods change chemical elements proportion measured by energy dispersive X-ray spectroscopy?. Biol. Trace Elem. Res. 196 (2020), 168–172, 10.1007/s12011-019-01909-x.
Lima, G.D. de A., Sertorio, M.N., Souza, A.C.F., Menezes, T.P., Mouro, V.G.S., Gonçalves, N.M., Oliveira, J.M. de, Henry, M., Machado-Neves, M., Fertility in male rats: disentangling adverse effects of arsenic compounds. Reprod. Toxicol. 78 (2018), 130–140, 10.1016/j.reprotox.2018.04.015.
Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randal, R.J., Protein measurement with the Folin phenol reagent. Anal. Biochem. 217 (1994), 220–230, 10.1016/0304-3894(92)87011-4.
Mather, A., Pollock, C., Glucose handling by the kidney. Kidney Int. 79 (2011), S1–S6, 10.1038/ki.2010.509.
Meng, J.-M., Cao, S.-Y., Wei, X.-L., Gan, R.-Y., Wang, Y.-F., Cai, S.-X., Xu, X.-Y., Zhang, P.-Z., Li, H.-B., Effects and mechanisms of tea for the prevention and management of diabetes mellitus and diabetic complications: an updated review. Antioxidants, 8, 2019, 170, 10.3390/antiox8060170.
Mineharu, Y., Koizumi, A., Wada, Y., Iso, H., Watanabe, Y., Date, C., Yamamoto, A., Kikuchi, S., Inaba, Y., Toyoshima, H., Kondo, T., Tamakoshi, A., Coffee, green tea, black tea and oolong tea consumption and risk of mortality from cardiovascular disease in Japanese men and women. J. Epidemiol. Community Health 65 (2011), 230–240, 10.1136/jech.2009.097311.
Mohabbulla Mohib, M., Fazla Rabby, S.M., Paran, T.Z., Mehedee Hasan, M., Ahmed, I., Hasan, N., Abu Taher Sagor, M., Mohiuddin, S., Protective role of green tea on diabetic nephropathy - a review. Cogent Biol., 2, 2016, 10.1080/23312025.2016.1248166.
Park, J.S., Kim, M.H., Chang, H.J., Kim, K.M., Kim, S.M., Shin, B.A., Ahn, B.W., Jung, Y.D., Epigallocatechin-3-gallate inhibits the PDGF-induced VEGF expression in human vascular smooth muscle cells via blocking PDGF receptor and Erk-1/2. Int. J. Oncol. 29 (2006), 1247–1252, 10.3892/ijo.29.5.1247.
Peixoto, E.B., Papadimitriou, A., Teixeira, D.A.T., Montemurro, C., Duarte, D.A., Silva, K.C., Joazeiro, P.P., Lopes de Faria, J.M., Lopes de Faria, J.B., Reduced LRP6 expression and increase in the interaction of GSK3β with p53 contribute to podocyte apoptosis in diabetes mellitus and are prevented by green tea. J. Nutr. Biochem. 26 (2015), 416–430, 10.1016/j.jnutbio.2014.11.012.
Perva-Uzunalić, A., Škerget, M., Knez, Ž., Weinreich, B., Otto, F., Grüner, S., Extraction of active ingredients from green tea (Camellia sinensis): extraction efficiency of major catechins and caffeine. Food Chem. 96 (2006), 597–605, 10.1016/j.foodchem.2005.03.015.
Rachid, A., Rabah, D., Farid, L., Zohra, S.F., Houcine, B., Ethnopharmacological survey of medicinal plants used in the traditional treatment of diabetes mellitus in the North Western and South Western Algeria. J. Med. Plants Res. 6 (2012), 2041–2050, 10.5897/JMPR11.1796.
Rebhan, M., Chalifa-Caspi, V., Prilusky, J., Lancet, D., GeneCards: a novel functional genomics compendium with automated data mining and query reformulation support. Bioinformatics 14 (1998), 656–664, 10.1093/bioinformatics/14.8.656.
Renno, W.M., Abdeen, S., Alkhalaf, M., Asfar, S., Effect of greean tea on kidney tubules of diabetic rats. Br. J. Nutr. 100 (2008), 652–659, 10.1017/S0007114508911533.
Ribback, S., Cigliano, A., Kroeger, N., Pilo, M.G., Terracciano, L., Burchardt, M., Bannasch, P., Calvisi, D.F., Dombrowski, F., PI3K/AKT/mTOR pathway plays a major pathogenetic role in glycogen accumulation and tumor development in renal distal tubules of rats and men. Oncotarget 6 (2015), 13036–13048, 10.18632/oncotarget.3675.
Ricart-Jané, D., Llobera, M., López-Tejero, M.D., Anticoagulants and other preanalytical factors interfere in plasma nitrate/nitrite quantification by the Griess method. Nitric Oxide - Biol. Chem. 6 (2002), 178–185, 10.1006/niox.2001.0392.
Sartippour, M.R., Heber, D., Zhang, L., Beatty, P., Elashoff, D., Elashoff, R., Go, V.L., Brooks, M.N., Inhibition of fibroblast growth factors by green tea. Int. J. Oncol. 21 (2002), 487–491, 10.3892/ijo.21.3.487.
Scardoni, G., Petterlini, M., Laudanna, C., Analyzing biological network parameters with CentiScaPe. Bioinformatics 25 (2009), 2857–2859, 10.1093/bioinformatics/btp517.
Shannon, P., Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13 (2003), 2498–2504, 10.1101/gr.1239303.
Silva, M.J., Brodt, M.D., Lynch, M.A., McKenzie, J.A., Tanouye, K.M., Nyman, J.S., Wang, X., Type 1 diabetes in young rats leads to progressive trabecular bone loss, cessation of cortical bone growth, and diminished whole bone strength and fatigue life. J. Bone Miner. Res. 24 (2009), 1618–1627, 10.1359/jbmr.090316.
Soetan, K.O., Olaiya, C.O., Oyewole, O.E., The importance of mineral elements for humans, domestic animals and plants: a review. Afr. J. Food Sci. 4 (2010), 200–222.
Su, J., Ye, D., Gao, C., Huang, Q., Gui, D., Mechanism of progression of diabetic kidney disease mediated by podocyte mitochondrial injury. Mol. Biol. Rep., 2020, 10.1007/s11033-020-05749-0.
Suzuki, T., Fujikura, K., Higashiyama, T., Takata, K., DNA staining for fluorescence and laser confocal microscopy. J. Histochem. Cytochem. 45 (1997), 49–53, 10.1177/002215549704500107.
Szklarczyk, D., Morris, J.H., Cook, H., Kuhn, M., Wyder, S., Simonovic, M., Santos, A., Doncheva, N.T., Roth, A., Bork, P., Jensen, L.J., Von Mering, C., The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 45 (2017), D362–D368, 10.1093/nar/gkw937.
Szklarczyk, D., Santos, A., Von Mering, C., Jensen, L.J., Bork, P., Kuhn, M., STITCH 5: augmenting protein-chemical interaction networks with tissue and affinity data. Nucleic Acids Res. 44 (2016), D380–D384, 10.1093/nar/gkv1277.
Tachibana, H., Koga, K., Fujimura, Y., Yamada, K., A receptor for green tea polyphenol EGCG. Nat. Struct. Mol. Biol. 11 (2004), 380–381, 10.1038/nsmb743.
Vallon, V., Thomson, S.C., Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia 60 (2017), 215–225, 10.1007/s00125-016-4157-3.
Van Aller, G.S., Carson, J.D., Tang, W., Peng, H., Zhao, L., Copeland, R.A., Tummino, P.J., Luo, L., Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor. Biochem. Biophys. Res. Commun. 406 (2011), 194–199, 10.1016/j.bbrc.2011.02.010.
Vaz, S.R., de Amorim, L.M.N., de Nascimento, P.V.F., Veloso, V.S.P., Nogueira, M.S., Castro, I.A., Mota, J.F., Botelho, P.B., Effects of green tea extract on oxidative stress and renal function in diabetic individuals: a randomized, double-blinded, controlled trial. J. Funct. Foods 46 (2018), 195–201, 10.1016/j.jff.2018.04.059.
Waltner-Law, M.E., Wang, X.L., Law, B.K., Hall, R.K., Nawano, M., Granner, D.K., Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production. J. Biol. Chem. 277 (2002), 34933–34940, 10.1074/jbc.M204672200.
Yamabe, N., Yokozawa, T., Oya, T., Kim, M., Therapeutic potential of (-)-Epigallocatechin 3- O -gallate on renal damage in diabetic nephropathy model rats. J. Pharmacol. Exp. Therapeut. 319 (2006), 228–236, 10.1124/jpet.106.107029.
Yang, X., Tomás-Barberán, F.A., Tea is a significant dietary source of ellagitannins and ellagic acid. J. Agric. Food Chem. 67 (2019), 5394–5404, 10.1021/acs.jafc.8b05010.
Yin, D.D., Luo, J.H., Zhao, Z.Y., Liao, Y.J., Li, Y., Tranilast prevents renal interstitial fibrosis by blocking mast cell infiltration in a rat model of diabetic kidney disease. Mol. Med. Rep. 17 (2018), 7356–7364, 10.3892/mmr.2018.8776.
Yokozawa, T., Noh, J.S., Park, C.H., Green tea polyphenols for the protection against renal damage caused by oxidative stress. Evidence-based Complement. Alternative Med., 2012, 10.1155/2012/845917 2012.
Yoon, S.P., Maeng, Y.H., Hong, R., Lee, B.R., Kim, C.G., Kim, H.L., Chung, J.H., Shin, B.C., Protective effects of epigallocatechin gallate (EGCG) on streptozotocin-induced diabetic nephropathy in mice. Acta Histochem. 116 (2014), 1210–1215, 10.1016/j.acthis.2014.07.003.
Yoshimura, M., Watanabe, Y., Kasai, K., Yamakoshi, J., Koga, T., Inhibitory effect of an ellagic acid-rich pomegranate extract on tyrosinase activity and ultraviolet-induced pigmentation. Biosci. Biotechnol. Biochem. 69 (2005), 2368–2373, 10.1271/bbb.69.2368.
Youn, H.S., Lee, J.Y., Saitoh, S.I., Miyake, K., Kang, K.W., Choi, Y.J., Hwang, D.H., Suppression of MyD88- and TRIF-dependent signaling pathways of toll-like receptor by (-)-epigallocatechin-3-gallate, a polyphenol component of green tea. Biochem. Pharmacol. 72 (2006), 850–859, 10.1016/j.bcp.2006.06.021.
Yu, H., Kim, P.M., Sprecher, E., Trifonov, V., Gerstein, M., The importance of bottlenecks in protein networks: correlation with gene essentiality and expression dynamics. PLoS Comput. Biol. 3 (2007), 713–720, 10.1371/journal.pcbi.0030059.
Zhang, X., Guo, K., Xia, F., Zhao, X., Huang, Z., Niu, J., FGF23 C-tail improves diabetic nephropathy by attenuating renal fibrosis and inflammation. BMC Biotechnol. 18 (2018), 1–9, 10.1186/s12896-018-0449-7.
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