Nefroprotektivno delovanje vodenog acetonskog ekstrakta Morus alba i mehanizam toksičnosti indukovane glifosatom - in vivo model
Sažetak
Glifosat, aktivna materija preparata Roundup®, je pesticid koji je u najširoj upotrebi u svetu i njegovi ostaci se mogu naći u prerađenoj hrani i pijaćoj vodi. Ranija istraživanja su potvrdila da ekstrakti lista Morus alba poseduju farmakološko dejstvo. Međutim, renoprotektivno delovanje ekstrakta M. alba i njihovog molekularnog mehanizma još uvek je nepoznato.
U ogledu su korišćeni laboratorijski beli pacovi (180-200 g) (n=5-6). Kontrolna grupa je intraperitonealno (i.p) dobijala 0.2 ml normalnog fiziološkog rastvora jednom u toku dana tokom dve nedelje. Kontrolnim životinjama je davana standardna hrana. Tretirane grupe su dobijale ili polifenolni ekstrakt (100 mg/kg, i.p) ili glifosat (100 mg/kg, i.p), ili pak njihovu smešu (ekstrakt μg ml−1 kg t.m. i glifosat 100 mg kg−1 t.m, i.p), jednom dnevno do petnaestog dana tretmana. Merene su vrednosti laktat dehidrogenaze LDH, koncentracije uree, kreatitina i azotmonoksida u serumu, a korišćene su standardne kolorometrijske metode.
Renalni oksidativni stress, konstatovan preko povišenih vrednosti malondialdehida (MDA) i nivoa proteinskih karbonila, kao i snižene aktivnosti superoksida dismutase (SOD), bio je značajno povišen delovanjem primenjenog ekstrakta lista duda (MLE). MLE je pokazao da može da modulira izmenjene biohemijske parameter održavanjem nivoa slobodnog gvožđa i homeostaze Ca2 +, kao i da reguliše endogeni sistem antioksidativnih enzima. Izgleda da istovremena primena vodenog acetonskog rastvora frakcije M. alba koji je bogat hlorogenom kiselinom i njenim izomerima može imati zaštitno delovanje na bubrege nakon nefrotoksične aktivnosti glifosata. Ukupno gledano, MLE može delovati zaštitno protiv toksičnosti indukovane
glifosatom, što se može pripisati hlorogenoj kiselini i njenim izomerima, koji predstavljaju najprisutnije fenolne kiseline u ekstraktima.
List belog duda je izvor fenolnih jedinjenja i stoga može predstavljati osnovu za potragu za novim hemijskim jedinjenjem koje će omogućiti dobijanje novog lekovitog sredstva. Suplement od ekstrakta belog duda može biti kandidat za razvoj bezbednog i perspektivnog preparata kao dodatka ishrani namenjenog zaštiti od nefrotoksičnosti.
Reference
Aebi, H. (1984). Catalase in vitro. Methods in Enzymology, 105, 121-126. doi.org/10.1016/S0076-6879(84)05016-3
Agrahari, S., Pandey, K., & Gopal, K. (2017). Biochemical alteration induced by monocrotophos in the blood plasma of fish, Channa punctatus (Bloch). Pesticide Biochemistry and Physiology, 88(3), 268-272. https://doi.org/10.1016/j.pestbp.2007.01.001
Astiz, M., De Alaniz, M.J.T., & Marra, C.A. (2009). Antioxidant defense system in rats simultaneously intoxicated with agrochemicals, Environmental Toxicology and Pharmacology, 28, 465-473. doi: 10.1016/j.etap.2009.07.009.
Bakris, G.L., Lass, N., Gaber, A.O., Jones, J.D., & Burnett, J.C. (1990). Radiocontrast medium-induced declines in renal function: A role for oxygen free radicals. Americal Journal of Physiology,258, 115-120. doi: 10.1152/ajprenal.1990.258.1.F115.
Baudin, E., Caron, P., Lombard-Bohas, C., Tabarin, A., Mitry, E., Reznick, Y. ... Do Cao, C. (2013). Malignant insulinoma: recommendations for characterisation and treatment,. Annales d’Endocrinolgie 74, 523-533. doi: 10.1016/j.ando.2013.07.001
Benedetti, A.L., De Lourdes Vituri, C., Trentin, A.G., Domingues, M.A.C., & Alvarez-Silva, M. (2004). The effects of sub-chronic exposure of Wistar rats to the herbicide glyphosate-biocarb. Toxicology Letters, 153, 227-232. doi: 10.1016/j.toxlet.2004.04.008.
Bradberry, S.M., Proudfoot, A.T., & Vale, J.A. (2004). Glyphosate poisoning. Toxicological Reviews, 23, 159-167.
Cavuşoğlu, K., Yapar, K., Oruc, E., & Yalcın, .E. (2011). Protective effect of Ginkgo biloba L. leaf extract against glyphosate toxicity in Swiss albino mice. Journal of Medicinal Food, 14, 1263-1272. doi: 10.1089/jmf.2010.0202
Chen, Y.C., Tien, Y.J., Chen, C.H., Beltan F.N., Amor, E.C., Wang, R.J. ... Yang, R.C. (2013). Morus alba and active compound oxyresveratrol exert anti-inflammatory activity via inhibition of leukocyte migration involving MEK/ERK signalling. BMC Complementary and Alternative Medicine, 13, Art. No. 45. doi: 10.1186/1472-6882-13-45
Chu, Q., Lin, M., Tian, X., &Ye, J. (2006). Study on capillary electrophoresis-amperometric detection profiles of different parts of M. alba L. Journal of Chromatography, A, 1116, 286–290.
Culbreth, M.E., Harrill, J.A., Freudenrich, T.M., Mundy, W.R., & Shafer, T.J. (2012). Comparison of chemicalinduced changes in proliferation and apoptosis in human and mouse neuroprogenitor cells. Neurotoxicology, 33, 1499-1510.
De Liz Oliveira Cavalli, L.V., Cattani, D., Heinz Rieg, C.E., Pierozan, P., Zanatta, L., Benedetti Parisotto, E… Zamoner, A. (2013). Roundup disrupts male reproductive functions by triggering calcium-mediated cell death in rat testis and Sertoli cells. Free Radical Biological Medecine, 65, 335–346. doi: doi.org/10.1016/j.freeradbiomed.2013.06.043
Domitrović, R., Cvijanović, O., Šušnić, V., & Katalinić, N. (2014). Renoprotective mechanisms of chlorogenic acid in cisplatin-induced kidney injury. Toxicology, 324, 98-107.
Draper, H.H., & Hadley, M. (1990). Malondialdehyde determination as index of lipid peroxidation. Methods in Enzymology, 186, 421-431.
Duke, J. A. & Ayensu, E. S. (1985). Medicinal plants of China (2 Vols). Journal of Botanical Taxonomy and Geobotany, Feddes Repertorium, 98, 398. doi.org/10.1002/fedr.19870980707
Dzoyem, J.P., & Eloff, J.N. (2014). Biochemical parameters in toxicological studies in Africa: Significance, principle of methods, data interpretation, and use in plant screenings. In Victor Kuete (ed.), Toxicological Survey of African Medicinal Plants (pp 659-715). London, UK: Elsevier. doi.org/10.1016/B978-0-12-800018-2.00023-6
El-Shenawy, N.S. (2009). Oxidative stress responses of rats exposed to Roundup and its active ingredient glyphosate. Environmental Toxicology and Pharmacology, 28, 379-385. doi: 10.1016/j.etap.2009.06.001.
Emami, A., Shams Ardekani, M.R., Mehregan, I. (2004). Color atlas of medicinal plants. Tehran, Iran: ITMRC Publications, 240.
Fang, N., Yu, S., & Prior, R.L. (2002). LC/MS/MS characterization of phenolic constituents in dried plums. Journal of Agricultural and Food Chemistry, 50, 3579-85.
Faqir, M., Zafar, M.V.S., Tanweer, K., Javed, I., & Saleemi, M.K. (2014). Nephroprotective effects of Morus Alba Linn against isoniazid-induced toxicity in albino rabbits. Pakistan Veterinary Journal, 34, 499-503.
Fattouch, S., Caboni, P., Tuberoso, C., Angioni, A., Dessi, S., Marzouki, M.N., Cabras, P. (2008). Comparative analysis of polyphenolic profiles and antioxidant and antimicrobial activities of Tunisian pome fruit pulp and peel aqueous acetone extracts. Journal of Agricultural and Food Chemistry, 56(3), 1084-1090. doi.org/10.1021/jf072409e
Hamdaoui, L., Naifar, M., Mzid, M., Ben Salem, M., Chtourou, A., Makni-Ayadi, F. ... Rebai, T. (2016). Nephrotoxicity of Kalach 360 SL: biochemical and histopathological findings. Toxicology Mechanisms and Methods, 26(9), 685-691.
Jin, S., Chang, C., Zhang, L., Liu, Y., Huang, X., & Chen, Z. (2015). Chlorogenic acid improves late diabetes through adiponectin receptor signaling pathways in db/db mice. PLoS ONE, 10(4), 120-842.
Jingqiu, L., Xiaoxia, G., Yinghua, X., Jing, C., Wei, L., & Yan, Z. (2016). Chlorogenic acid slows down proteinuria and renal fibrosis in 5/6-nephrectomized rats by anti-oxidation and inhibiting accumulation of extracellular matrix. International Journal of Clinical and Experimental Medicine, 9(8), 15719-15727.
Kaneto, H., Fujii, J., Suzuki, K.,. Kasai, H., Kawamori, R., Kamada, T., & Taniguchi, N. (1994). DNA cleavage induced by glycation of Cu, Zn-superoxide dismutase. Biochemical Journal, 304, 219-225.
Kapil, A., Koul, I.B., & Suri, O.P. (1995). Antihepatotoxic effects of chlorogenic acid from Anthocephalus cadamba. Phytotherapy Research, 9, 189. doi: doi.org/10.1002/ptr.2650090307
Kawagashira, Y., Koike, H., Kawabata, K., Takahashi, M., Ohyama, K., Hashimoto, R. ... Sobue, G. (2017). Vasculitic neuropathy following exposure to a glyphosate-based herbicide. Internal Medicine, 56, 1431-1434.
Kobayashi, Y., Miyazawa, M., & Kojima, T. (2011). The use of Morus alba L.(mulberry) and Eucommia ulmoides (Tochu) leaves as functional foods: a promising approach in the management of hyperlipidemia. Journal of Traditional Medicine, 27, 225-230.
Larsen, K. (1972). Creatinine assay by a reaction-kinetic principle. Clinica Chimica Acta, 41, 209-17. doi: 10.1016/0009-8981(72)90513-x.
Leardi, A., Caraglia, M., Selleri, C., Pepe, S., Pizzi, C., Notaro, R. ... Tagliaferri, P. (1998). Desferioxamine increases iron depletion and apoptosis induced by ara-C of human myeloid leukaemic cells. British Journal of Haematology, 102, 746-752.
Lee, C.Y., Sim, S.M., & Cheng, H.M. (2007). Systemic absorption of antioxidants from mulberry (Morus alba L) leaf extracts using an in situ rat intestinal preparation. Nutrition Research, 27, 492-497. doi: 10.1016/J.NUTRES.2007.06.004
Mansour, S.A., & Mossa, A.H. (2010). Oxidative damage, biochemical and histopathological alterations in rats exposed to chlorpyrifos and the antioxidant role of zinc. Pesticide Biochemistry and Physiology, 96, 14-23.
Marc, J., Breton, M.L., Cormier, P., Morales, J., Belle, R., & Mulner Lorillon, O.A. (2005). A glyphosatebased pesticide impinges on transcription. Toxicology and Applied Pharmacology, 203, 1-8. doi: 10.1016/j.taap.2004.07.014
McCord, J.M., Keele, B.B., & Fridovic, I. (1971). An enzymebased theory of obligate anaerobiosis: the physiological function of superoxide dismutase. Proceedings of the National Academy of Sciences of the USA, 68, 1024-1027.
Mensah, P.K., Palmer, C.G., Muller, W.J. (2012). Lipid peroxidation in the freshwater shrimp Caridina nilotica as a biomarker of Roundup herbicide pollution of freshwater systems in South Africa. Water Science and Technology, 65, 1660-1666.
Mesnage, R., Arno, M., Costanzo, M., Malatesta, M., Seralini, G.E., Antoniou, M.N. (2015). Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure. Environmental Health, 14, 70.
Misra, H.P., & Fridovich, I. (1972). The role of superoxide anion in autoxidation of epinephrine and a simple assay for superoxide dismutase. Journal of Biological Chemistry, 247, 3170- 3175.
Mohamed,F., Endre, Z.H., Pickering, J.W., Jayamanne, S., Palangasinghe, C., Shahmy, S. … Buckley, N.A. (2016). Mechanism-specific injury biomarkers predict nephrotoxicity early following glyphosate surfactant herbicide (GPSH) poisoning. Toxicology Letters, 7, 258, 1-10.
Naowaboot, J., Pannangpetch, P., Kukongviriyapan, V., Kongyingyoes, B., & Kukongviriyapan, U. (2004). Antihyperglycemic, antioxidant and antiglycation activities of mulberry leaf extract in streptozotocininduced chronic diabetic rats. Plant Foods for Human Rationion, 64, 116-121.
Naqvi, R. (2017). Acute kidney injury from different poisonous substances. World Journal of Nephrology, 6(3), 162–167.
Navarro, C.D., & Martinez, C.B. (2014). Effects of the surfactant polyoxyethylene amine (POEA) on genotoxic, biochemical and physiological parameters of the freshwater teleost Prochilodus lineatus. Comparative Biochemistry and Physiology, C - Toxicology and Pharmacology, 165, 83-90.
Ullah, N., Khan, M.A., Khan, S., Ahman, H., Asif, A.H., & Khan, T. (2016), Nephro-protective potential of Morus alba, a prospective experimental study on animal models, Pharmaceutical Biology, 54, 530-535.
Negga, R., Stuart, J.A., Machen, M.L., Salva, J., Lizek, A.J., Richardson, S.J. … Fitsanakis V.A. (2012). Exposure to glyphosate- and/or Mn/Zn-ethylenebisdithiocarbamatecontaining pesticides leads to degeneration of γ-aminobutyric acid and dopamine neurons in Caenorhabditis elegans. Neurotoxicity Research, 21, 281–290.
Nematbakhsh, M., Hajhashemi, V., Ghannadi, A., Talebi, A., & Nikahd, M. (2013). Protective effects of the Morus alba L. leaf extracts on cisplatininduced nephrotoxicity in rats. Research in Pharmaceutical Sciences, 8(2), 71-77.
Nickavar, B., & Mosazadeh, G. (2009). Influence of three Morus species extracts on α-amylase activity. Iranian Journal of Pharmaceutical Research, 8(2),115-119.
Ohnishi, S.T., & Barr, J.K. (1978). A simple method of quantitating protein using the biuret and phenol reagent. Analitical Biochemistry, 86, 193-200.
Peluso, M., Munnia, A., Bolognesi, C., & Parodi, S. (1998). 32P-postlabeling detection of DNA adducts in mice treated with the herbicide Roundup. Environmental and Molecular Mutagenesis 31, 55-59.
Rebai, O., Belkhir, M., Boujelben, A., Fattouch, S., & Amri, M. (2017). Morus alba leaf extract mediates neuroprotection against glyphosate-induced toxicity and biochemical alterations in the brain. Environmental Science and Pollution Research International, 24(10), 9605-9613.
Rizvi, S.I., & Maurya, P.K. (2007). Markers of oxidative stress in erythrocytes during aging in humans. Annals of the New York Academy of Sciences, 1100, 373-382.
Sadighara, P., & Barin, A. (2010). The study of antioxidant potential of Morus alba L. leaves extract. Journal of Herbal Drugs, 1(3),43-46.
Salih, N.D., Hazir, M.N.S., & Abo Hamid, M.H. (2015). The effect of mulberry (Morus sp.) tea supplementation on acetaminophen induced renal failure in rats. World Journal of Pharmacy and Pharmaceutical Sciences, 4(4), 111-125.
Sanchez-Salcedo, E.M., Mena, P., Garcia-Viguera, C.,& Hernandez, F. ( 2015). Phytochemical evaluation of white (Morus alba L.) and black (Morus nigra L.) mulberry fruits, a starting point for the assessment of their beneficial properties. Journal of Functional Foods, 12, 399-408.
Seok, S.J., Park, J.S., Hong, J.R., Gil, H.W., Yang, J.O., Lee, E.Y. ... Hong, S.Y. (2011). Surfactant volume is an essential element in human toxicity in acute glyphosate herbicide intoxication. Clinical Toxicology (Phila), 49(10), 892-899.
Shehata, A.A., Schrodl, W., Schledorn, P., & Kruger, M. (2014). Distribution of glyphosate in chicken organs and its reduction by humic acid supplementation. Journal of Poultry Science, 51(3), 333.
Sribanditmongkol, P., Jutavijittum, P., Pongraveevongsa, P., Wunnapuk, K., & Durongkadech, P. (2012). Pathological and toxicological findings in glyphosatesurfactant herbicide fatality: A case report. The American Journal of Forensic Medicine and Pathology, 33(3), 234-237.
Stern, J., & Lewis, W.H. (1957). The colorimetric estimation of calcium in serum with ocresolphthalein complexone. Clinica Chimica Acta, 2, 576-580.
Suzuki, A., Yamamoto, N., Jokura, H., Yamamoto, M., Fujii, A., Tokimitsu, I. & Saito, I. (2006). Chlorogenic acid attenuates hypertension and improves endothelial function in spontaneously hypertensive rats. Journal of Hypertension, 24, 1065-1073.
Thabti, I., Elfalleh, W., Hannachi, H., Ferchichi, A., & Campos, M.D.G. (2012). Identification and quantification of phenolic acids and flavonol glycosides in Tunisian Morus species by HPLC-DAD and HPLCMS. Journal of Functional Foods, 4, 367-374.
Valcke, M., Levasseur, M.E., Da Silva, A.S., & Wesseling, C. (2017). Pesticide exposures and chronic kidney disease of unknown etiology: an epidemiologic review. Environmental Health, 16, 49.
Wang, J., Wu, F.A, Zhao, H. Liu, L., & Wu, Q.S. (2008). Isolation of flavonoids from mulberry (Morus alba L.) leaves with macroporous resins. African Journal of Biotechnology, 7(13), 2147-2155.
Wei, K., Yin, Z., & Xie, Y. (2016). Roles of the kidney in the formation, remodeling and repair of bone. Journal of Nephrology, 29, 349-357.
Wunnapuk, K., Gobe, G., Endre, Z., Peake, P., Grice, J., Roberts, M.S. ... Liu, X. (2014). Use of a glyphosate-based herbicide-induced nephrotoxicity model to investigate a panel of kidney injury biomarkers. Toxicology Letters, 225, 192–200.
Yang Y, Gong T, Liu C, Chen RY (2010). Four new 2-arylbenzofuran derivatives from leaves of Morus alba L. Chemical and Pharmacelutical Bulletin, 58(2), 257-60.
Yeung, H.C. (1985). Handbook of Chinese herbs and formulas, Vol 1. Taos, NM, USA: Redwing Book.
Zhang, F., Pan, L.P., Ding, E.M., Ge, Q.J., Zhang, Z.H., Xu, J.N., Zhang, L., & Zhu, B.L. (2017). Study of the effect of occupational exposure to glyphosate on hepatorenal function. Zhonghua Yu Fang Yi Xue Za Zhi, 51(7), 615-620.
Zhao, Y., Wang, J., Ballevre, O., Luo, H. & Zhang, W. (2012). Antihypertensive effects and mechanisms of chlorogenic acids. Hypertension Research, 35, 370-374.
- Autori zadržavaju autorska prava i pružaju časopisu pravo prvog objavljivanja rada i licenciraju ga "Creative Commons Attribution licencom" koja omogućava drugima da dele rad, uz uslov navođenja autorstva i izvornog objavljivanja u ovom časopisu.
- Autori mogu izraditi zasebne, ugovorne aranžmane za neekskluzivnu distribuciju članka objavljenog u časopisu (npr. postavljanje u institucionalni repozitorijum ili objavljivanje u knjizi), uz navođenje da je članak izvorno objavljen u ovom časopisu.
- Autorima je dozvoljeno i podstiču se da postave objavljeni članak onlajn (npr. u institucionalni repozitorijum ili na svoju internet stranicu) pre ili tokom postupka prijave rukopisa, s obzirom da takav postupak može voditi produktivnoj razmeni ideja i ranijoj i većoj citiranosti objavljenog članka (Vidi Efekti otvorenog pristupa).