Potential nephroprotective effects of resveratrol in drug induced nephrotoxicity: a narrative review of safety and efficacy data

Advances in Traditional Medicine - Tập 20 - Trang 529-544 - 2020
Foroud Shahbazi1,2, Fakhrossadat Farvadi3, Simin Dashti-Khavidaki4, Sara Ataei5, Lida Shojaei1,2
1Department of Clinical Pharmacy, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
2Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
3Department of Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
4Liver Transplantation Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
5Department of Clinical Pharmacy, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran

Tóm tắt

Drug induced nephrotoxicity commonly occurs in hospitalized patients and sometimes may complicate treatment outcome, especially in critically ill patients. No universal prophylactic agent is available yet to protect against drug related nephrotoxicity. Many modalities have been applied with different successes. Polyphenolic compounds such as resveratrol have been used both in-vitro and in vivo to prevent drug induced nephrotoxicity. Resveratrol have several antioxidant, antiplatelet and nitric oxide releasing properties in preclinical studies. In this review, we discuss recent studies that evaluated resveratrol protective effects, the mechanism of action and safety issues on drug induced nephrotoxicity.

Tài liệu tham khảo

Al Dera HS (2016) Protective effect of resveratrol against aluminum chloride induced nephrotoxicity in rats. Saudi Med J 37(4):369. https://doi.org/10.15537/smj.2016.4.13611 Albertoni G, Schor N (2015) Resveratrol plays important role in protective mechanisms in renal disease-mini-review. J Bras Nefrol 37(1):106–114 Alexander JW, Metze TJ, McIntosh MJ, Goodman HR, First MR, Munda R, Safdar S (2005) The influence of immunomodulatory diets on transplant success and complications. Transplantation 79(4):460–465 Amudha G, Josephine A, Varalakshmi P (2006) Role of lipoic acid in reducing the oxidative stress induced by cyclosporine A. Clin Chim Acta 372(1–2):134–139 Ansari KA, Vavia PR, Trotta F, Cavalli R (2011) Cyclodextrin-based nanosponges for delivery of resveratrol: in vitro characterisation, stability, cytotoxicity and permeation study. AAPS Pharmscitech 12(1):279–286 Basavaraj S, Betageri GV (2014) Improved oral delivery of resveratrol using proliposomal formulation: investigation of various factors contributing to prolonged absorption of unmetabolized resveratrol. Exp Opin Drug Deliv 11(4):493–503 Benesic A, Schwerdt G, Hennemeier I, Sauvant C, Mildenberger S, Gekle M (2014) The nephrotoxic Ifosfamide-metabolite chloroacetaldehyde interferes with renal extracellular matrix homeostasis. Cell Physiol Biochem 33(4):1106–1116 Berman AY, Motechin RA, Wiesenfeld MY, Holz MK (2017) The therapeutic potential of resveratrol: a review of clinical trials. NPJ Precis Oncol 1(1):35 Bienholz A, Pang RM, Guberina H, Rauen U, Witzke O, Wilde B, Kribben A (2017) Resveratrol does not protect from ischemia-induced acute kidney injury in an in vivo rat model. Kidney Blood Press R 42(6):1090–1103 Bonechi C, Martini S, Ciani L, Lamponi S, Rebmann H, Rossi C, Ristori S (2012) Using liposomes as carriers for polyphenolic compounds: the case of trans-resveratrol. PLoS ONE 7(8):e41438. https://doi.org/10.1371/journal.pone.0041438 Bradamante S, Barenghi L, Villa A (2004) Cardiovascular protective effects of resveratrol. Cardiovasc Drug Rev 22(3):169–188 Brasnyó P, Molnár GA, Mohás M, Markó L, Laczy B, Cseh J, Halmai R (2011) Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr 106(3):383–389 Burdmann EA, Andoh TF, Yu L, Bennett WM (2003) Cyclosporine nephrotoxicity. Semin Nephrol 23(5):465–476 Cai S, Yang Q, Bagby TR, Forrest ML (2011) Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles. Adv Drug Deliv Rev 63(10–11):901–908 Carter LG, D'Orazio JA, Pearson KJ (2014) Resveratrol and cancer: focus on in vivo evidence. Endocr Relat Cancer 21(3):R209–R225. https://doi.org/10.1530/ERC-13-0171 Chander V, Chopra K (2005) Role of nitric oxide in resveratrol-induced renal protective effects of ischemic preconditioning. J Vasc Surg 42(6):1198–1205 Chander V, Chopra K (2006) Protective effect of nitric oxide pathway in resveratrol renal ischemia-reperfusion injury in rats. Arch Med Res 37(1):19–26 Chander V, Tirkey N, Chopra K (2005) Resveratrol, a polyphenolic phytoalexin protects against cyclosporine-induced nephrotoxicity through nitric oxide dependent mechanism. Toxicology 210(1):55–64 Chen JM, Bai JY, Yang KX (2018) Effect of resveratrol on doxorubicin resistance in breast neoplasm cells by modulating PI3K/Akt signaling pathway. IUBMB Life 70(6):491–500 Cid TP, Garcıa JC, Alvarez FC, De Arriba G (2003) Antioxidant nutrients protect against cyclosporine A nephrotoxicity. Toxicology 189(1–2):99–111 Clément M-V, Hirpara JL, Chawdhury S-H, Pervaiz S (1998) Chemopreventive agent resveratrol, a natural product derived from grapes, triggers CD95 signaling-dependent apoptosis in human tumor cells. Blood 92(3):996–1002 Colombo M, Cassano N, Bellia G, Vena G (2013) Cyclosporine regimens in plaque psoriasis: an overview with special emphasis on dose, duration, and old and new treatment approaches. ScientificWorldJournal. https://doi.org/10.1155/2013/805705 Crowell JA, Korytko PJ, Morrissey RL, Booth TD, Levine BS (2004) Resveratrol-associated renal toxicity. Toxicol Sci 82(2):614–619 Darwish MA, Abo-Youssef AM, Khalaf MM, Abo-Saif AA, Saleh IG, Abdelghany TM (2018) Resveratrol influences platinum pharmacokinetics: a novel mechanism in protection against cisplatin-induced nephrotoxicity. Toxicol Lett 290:73–82 De Nicola L, Thomson SC, Wead LM, Brown MR, Gabbai FB (1993) Arginine feeding modifies cyclosporine nephrotoxicity in rats. J Clin Invest 92(4):1859–1865 Dera HA, Abushouk A (2015) Protective effect of resveratrol against aluminium chloride (AlCl3) induced testicular damage in rats entails inhibition of intrinsic apoptotic pathway. Sci Adv Mater 7(2):384–395 Do Amaral CL, Francescato HDC, Coimbra TM, Costa RS, Darin JDAC, Antunes LMG, Bianchi MDLP (2008) Resveratrol attenuates cisplatin-induced nephrotoxicity in rats. Arch Toxicol 82(6):363–370 Dubourg L, Michoudet C, Cochat P, Baverel G (2001) Human kidney tubules detoxify chloroacetaldehyde, a presumed nephrotoxic metabolite of ifosfamide. J Am Soc Nephrol 12(8):1615–1623 El-Kashef D, El-Kenawi A, Suddek G, Salem H (2017) Allicin ameliorates kidney function and urinary bladder sensitivity in cyclosporine A-treated rats. Hum Exp Toxicol 36(7):681–691 El-Shitany NA, El-Haggar S, El-Desoky K (2008) Silymarin prevents adriamycin-induced cardiotoxicity and nephrotoxicity in rats. Food Chem Toxicol 46(7):2422–2428 El-Sheikh AA, Morsy MA, Al-Taher AY (2016) Protective mechanisms of resveratrol against methotrexate-induced renal damage may involve BCRP/ABCG2. Fundam Clin Pharmacol 30(5):406–418 Galletti P, Di Gennaro CI, Migliardi V, Indaco S, Della Ragione F, Manna C, Zappia V (2005) Diverse effects of natural antioxidants on cyclosporin cytotoxicity in rat renal tubular cells. Nephrol Dial Transpl 20(8):1551–1558 Gambini J, Inglés M, Olaso G, Lopez-Grueso R, Bonet-Costa V, Gimeno-Mallench L, Vina J (2015) Properties of resveratrol: in vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. Oxid Med Cell Longev 2015:837042. https://doi.org/10.1155/2015/837042 Gan Y, Tao S, Cao D, Xie H, Zeng Q (2017) Protection of resveratrol on acute kidney injury in septic rats. Hum Exp Toxicol 36(10):1015–1022 Garvin S, Öllinger K, Dabrosin C (2006) Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo. Cancer Lett 231(1):113–122 Gehm BD, McAndrews JM, Chien P-Y, Jameson JL (1997) Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci 94(25):14138–14143 Gokce EH, Korkmaz E, Dellera E, Sandri G, Bonferoni MC, Ozer O (2012) Resveratrol-loaded solid lipid nanoparticles versus nanostructured lipid carriers: evaluation of antioxidant potential for dermal applications. Int J Nanomed 7:1841. https://doi.org/10.2147/IJN.S29710 Goldhahn K, Schmetterer K, Steiner G, Hintersteininger M, Erker T, Kloesch B (2015) A8. 20 A novel resveratrol prodrug: anti-proliferative and pro-apoptotic effects in human T-cells. Ann Rheum Dis 74(1):A89–A90. https://doi.org/10.1136/annrheumdis-2015-207259.205 Guo W, Li A, Jia Z, Yuan Y, Dai H, Li H (2013) Transferrin modified PEG-PLA-resveratrol conjugates: in vitro and in vivo studies for glioma. Eur J Pharmacol 718(1–3):41–47 Hao Q, Xiao X, Zhen J, Feng J, Song C, Jiang B, Hu Z (2016) Resveratrol attenuates acute kidney injury by inhibiting death receptor-mediated apoptotic pathways in a cisplatin-induced rat model. Mol Med Rep 14(4):3683–3689 Harde H, Das M, Jain S (2011) Solid lipid nanoparticles: an oral bioavailability enhancer vehicle. Exp Opin Drug Deliv 8(11):1407–1424 Holthoff JH, Wang Z, Seely KA, Gokden N, Mayeux PR (2012) Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury. Kidney Int 81(4):370–378 Hui Y, Lu M, Han Y, Zhou H, Liu W, Li L, Jin R (2017) Resveratrol improves mitochondrial function in the remnant kidney from 5/6 nephrectomized rats. Acta Histochem 119(4):392–399 Ibrahim A, Al-Hizab FA, Abushouk AI, Abdel-Daim MM (2018) Nephroprotective effects of benzyl isothiocyanate and resveratrol against cisplatin-induced oxidative stress and inflammation. Front Pharmacol. https://doi.org/10.3389/fphar.2018.01268 Jafari A, Dashti-Khavidaki S, Khalili H, Lessan-Pezeshki M (2013) Potential nephroprotective effects of l-carnitine against drug-induced nephropathy: a review of literature. Exp Opin Drug Saf 12(4):523–543 Jang I, Kim E, Lim J, Kim M, Ban T, Yoon H, Choi B (2018) Effects of resveratrol on the renin-angiotensin system in the aging kidney. Nutrients 10(11):1741 Kaloyanides GJ, Pastoriza-Munoz E (1980) Aminoglycoside nephrotoxicity. Kidney Int 18(5):571–582 Kane-Gill SL, Goldstein SL (2015) Drug-induced acute kidney injury: a focus on risk assessment for prevention. Crit Care Clin 31(4):675–684 Kane-Gill SL, Smithburger PL, Kashani K, Kellum JA, Frazee E (2017) Clinical relevance and predictive value of damage biomarkers of drug-induced kidney injury. Drug Saf 40(11):1049–1074 Kim DH, Jung YJ, Lee JE, Lee AS, Kang KP, Lee S, Ramkumar KM (2011) SIRT1 activation by resveratrol ameliorates cisplatin-induced renal injury through deacetylation of p53. Am J Physiol Ren Physiol 301(2):F427–F435 Kitada M, Koya D (2013) Renal protective effects of resveratrol. Oxid Med Cell Longev. https://doi.org/10.1155/2013/568093 Koda-Kimble MA (2012) Koda-Kimble and Young's applied therapeutics: the clinical use of drugs. Lippincott Williams & Wilkins, Philadelphia Kuypers DR, Neumayer HH, Fritsche L, Budde K, Rodicio JL, Vanrenterghem Y, Group LS (2004) Calcium channel blockade and preservation of renal graft function in cyclosporine-treated recipients: a prospective randomized placebo-controlled 2-year study. Transplantation 78(8):1204–1211 Launay-Vacher V, Rey J-B, Isnard-Bagnis C, Deray G, Daouphars M (2008) Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Cancer Chemother Pharmacol 61(6):903–909 Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blumberg JB (2008) Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst 100(11):773–783 Lin C-T, Sun X-Y, Lin A-X (2016) Supplementation with high-dose trans-resveratrol improves ultrafiltration in peritoneal dialysis patients: a prospective, randomized, double-blind study. Ren Fail 38(2):214–221 Lin Y-F, Lee Y-H, Hsu Y-H, Chen Y-J, Lin Y-F, Cheng F-Y, Chiu H-W (2017) Resveratrol-loaded nanoparticles conjugated with kidney injury molecule-1 as a drug delivery system for potential use in chronic kidney disease. Nanomedicine 12(22):2741–2756 Liu F-C, Tsai H-I, Yu H-P (2015) Organ-protective effects of red wine extract, resveratrol, in oxidative stress-mediated reperfusion injury. Oxid Med Cell Longev. https://doi.org/10.1155/2015/568634 Liu S, Zhao M, Zhou Y, Wang C, Yuan Y, Li L, Lu Y (2019) Resveratrol exerts dose-dependent anti-fibrotic or pro-fibrotic effects in kidneys: a potential risk to individuals with impaired kidney function. Phytomedicine 57:223–235 Lorenz P, Roychowdhury S, Engelmann M, Wolf G, Horn TF (2003) Oxyresveratrol and resveratrol are potent antioxidants and free radical scavengers: effect on nitrosative and oxidative stress derived from microglial cells. Nitric Oxide 9(2):64–76 Lu Z, Cheng B, Hu Y, Zhang Y, Zou G (2009) Complexation of resveratrol with cyclodextrins: solubility and antioxidant activity. Food Chem 113(1):17–20 Luo C-J, Luo F, Bu Q-D, Jiang W, Zhang W, Liu X-M, Ma R-X (2019) Protective effects of resveratrol on acute kidney injury in rats with sepsis. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. https://doi.org/10.5507/bp.2019.006 Mahmood WA, Mshimesh BAR, Khazaal FAK, Jasim SY, Mahmood AA (2018) Potential effects of resveratrol on obesity-related nephropathy in Iraqi obese women. J Pharm Sci Rev Res 10(5):999–1005 Mattarei A, Azzolini M, Carraro M, Sassi N, Zoratti M, Paradisi C, Biasutto L (2013) Acetal derivatives as prodrugs of resveratrol. Mol Pharm 10(7):2781–2792 Mattarei A, Azzolini M, La Spina M, Zoratti M, Paradisi C, Biasutto L (2015) Amino acid carbamates as prodrugs of resveratrol. Sci Rep 5:15216. https://doi.org/10.1038/srep15216 Meng X, Maliakal P, Lu H, Lee M-J, Yang CS (2004) Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after ingestion of pure compounds and grape juice. J Agr Food Chem 52(4):935–942 Meng J, Guo F, Xu H, Liang W, Wang C, Yang X-D (2016) Combination therapy using co-encapsulated resveratrol and paclitaxel in liposomes for drug resistance reversal in breast cancer cells in vivo. Sci Rep 6:22390. https://doi.org/10.1038/srep22390 Miller RP, Tadagavadi RK, Ramesh G, Reeves WB (2010) Mechanisms of cisplatin nephrotoxicity. Toxins 2(11):2490–2518 Mingeot-Leclercq M-P, Tulkens PM (1999) Aminoglycosides: nephrotoxicity. Antimicrob Agents Chemother 43(5):1003–1012 Mokni M, Hamlaoui S, Kadri S, Limam F, Amri M, Marzouki L, Aouani E (2016) Grape seed and skin extract protects kidney from doxorubicin-induced oxidative injury. Pak J Pharm Sci 29(3):961–968 Montsko G, Nikfardjam MSP, Szabo Z, Boddi K, Lorand T, Ohmacht R, Mark L (2008) Determination of products derived from trans-resveratrol UV photoisomerisation by means of HPLC–APCI-MS. J Photochem Photobiol A Chem 196(1):44–50 Morales AI, Buitrago JM, Santiago JM, Fernández-Tagarro M, López-Novoa JM, Pérez-Barriocanal F (2002) Protective effect of trans-resveratrol on gentamicin-induced nephrotoxicity. Antioxid Redox Signal 4(6):893–898 Morales AI, Rodríguez-Barbero A, Vicente-Sánchez C, Mayoral P, López-Novoa JM, Pérez-Barriocanal F (2006) Resveratrol inhibits gentamicin-induced mesangial cell contraction. Life Sci 78(20):2373–2377 Moyano-Mendez JR, Fabbrocini G, De Stefano D, Mazzella C, Mayol L, Scognamiglio I, De Rosa G (2014) Enhanced antioxidant effect of trans-resveratrol: potential of binary systems with polyethylene glycol and cyclodextrin. Drug Dev Ind Pharm 40(10):1300–1307 Naesens M, Kuypers DR, Sarwal M (2009) Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 4(2):481–508 Narayanan NK, Nargi D, Randolph C, Narayanan BA (2009) Liposome encapsulation of curcumin and resveratrol in combination reduces prostate cancer incidence in PTEN knockout mice. Int J Cancer 125(1):1–8 Nasiri-Toosi Z, Dashti-Khavidaki S, Khalili H, Lessan-Pezeshki M (2013) A review of the potential protective effects of pentoxifylline against drug-induced nephrotoxicity. Eur J Clin Pharmacol 69(5):1057–1073 Neves AR, Queiroz JF, Reis S (2016) Brain-targeted delivery of resveratrol using solid lipid nanoparticles functionalized with apolipoprotein E. J Nanobiotechnol 14(1):27 Nøhr-Meldgaard K, Ovsepian A, Ingmer H, Vestergaard M (2018) Resveratrol enhances the efficacy of aminoglycosides against Staphylococcus aureus. Int J Antimicrob Agents 52(3):390–396 Osman A-MM, Telity SA, Damanhouri ZA, Al-Harthy SE, Al-Kreathy HM, Ramadan WS, Kamel F (2015) Chemosensitizing and nephroprotective effect of resveratrol in cisplatin–treated animals. Cancer Cell Int 15(1):6 Pannu N, Nadim MK (2008) An overview of drug-induced acute kidney injury. Crit Care Med 36(4):S216–S223. https://doi.org/10.1097/CCM.0b013e318168e375 Patel KR, Scott E, Brown VA, Gescher AJ, Steward WP, Brown K (2011) Clinical trials of resveratrol. Ann N Y Acad Sci 1215(1):161–169 Popat R, Plesner T, Davies F, Cook G, Cook M, Elliott P, Cavenagh J (2013) A phase 2 study of SRT 501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma. Br J Haematol 160(5):714–717 Rauf A, Imran M, Butt MS, Nadeem M, Peters DG, Mubarak MS (2018) Resveratrol as an anti-cancer agent: A review. Crit Rev Food Sci Nutr 58(9):1428–1447 Saldanha JF, Leal VO, Rizzetto F, Grimmer GH, Ribeiro-Alves M, Daleprane JB, Mafra D (2016) Effects of resveratrol supplementation in Nrf2 and NF-κB expressions in nondialyzed chronic kidney disease patients: A randomized, double-blind, placebo-controlled, crossover clinical trial. J Ren Nutr 26(6):401–406 Şehirli Ö, Şakarcan A, Velioğlu-Öğünç A, Çetinel Ş, Gedik N, Yeğen BÇ, Şener G (2007) Resveratrol improves ifosfamide-induced Fanconi syndrome in rats. Toxicol Appl Pharmacol 222(1):33–41 Shahbazi F, Sadighi S, Dashti-Khavidaki S, Shahi F, Mirzania M, Abdollahi A, Ghahremani MH (2015) Effect of silymarin administration on cisplatin nephrotoxicity: report from a pilot, randomized, double-blinded, placebo-controlled clinical trial. Phytother Res 29(7):1046–1053 Siddalingappa B, Benson HA, Brown DH, Batty KT, Chen Y (2015) Stabilization of resveratrol in blood circulation by conjugation to mPEG and mPEG-PLA polymers: investigation of conjugate linker and polymer composition on stability, metabolism, antioxidant activity and pharmacokinetic profile. PLoS ONE 10(3):e0118824 Siddik ZH (2003) Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22(47):7265. https://doi.org/10.1038/sj.onc.1206933 Silan C, Uzun Ö, Çomunoglu NÜ, Gokçen S, Bedirhan S, Cengiz M (2007) Gentamicin-induced nephrotoxicity in rats ameliorated and healing effects of resveratrol. Biol Pharm Bull 30(1):79–83 Singh CK, Ndiaye MA, Ahmad N (2015) Resveratrol and cancer: challenges for clinical translation. Biochim Biophys Acta 1852(6):1178–1185 Smoliga JM, Baur JA, Hausenblas HA (2011) Resveratrol and health—a comprehensive review of human clinical trials. Mol Nutr Food Res 55(8):1129–1141 Su J-Q, Wen Z, Wen Y-A, Xiao W-N, Lin J, Zheng Z-K (2016) Modification and stabilizing effects of PEG on resveratrol-loaded solid lipid nanoparticles. J Iran Chem Soc 13(5):881–890 Summerlin N, Soo E, Thakur S, Qu Z, Jambhrunkar S, Popat A (2015) Resveratrol nanoformulations: challenges and opportunities. Int J Pharm 479(2):282–290 Sun L-J, Sun Y-N, Chen S-J, Liu S, Jiang G-R (2017) Resveratrol attenuates skeletal muscle atrophy induced by chronic kidney disease via MuRF1 signaling pathway. Biochem Biophys Res Commun 487(1):83–89 Tacar O, Sriamornsak P, Dass CR (2013) Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol 65(2):157–170 Tatsioni A, Chung M, Sun Y, Kupelnick B, Lichtenstein AH, Perrone R, Bonis PA (2005) Effects of fish oil supplementation on kidney transplantation: a systematic review and meta-analysis of randomized, controlled trials. J Am Soc Nephrol 16(8):2462–2470 Turner RS, Thomas RG, Craft S, van Dyck CH, Mintzer J, Reynolds BA, Aisen PS (2015) A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology 85(16):1383–1391 Valentovic MA, Ball JG, Brown JM, Terneus MV, McQuade E, Van Meter S, Williams T (2014) Resveratrol attenuates cisplatin renal cortical cytotoxicity by modifying oxidative stress. Toxicol In Vitro 28(2):248–257 Vang O, Ahmad N, Baile CA, Baur JA, Brown K, Csiszar A, Lin H-Y (2011) What is new for an old molecule? Systematic review and recommendations on the use of resveratrol. PLoS ONE 6(6):e19881. https://doi.org/10.1371/journal.pone.0019881 Varoni EM, Lo Faro AF, Sharifi-Rad J, Iriti M (2016) Anticancer molecular mechanisms of resveratrol. Front Nutr 3:8. https://doi.org/10.3389/fnut.2016.00008 Venkatesan N, Punithavathi D, Arumugam V (2000) Curcumin prevents adriamycin nephrotoxicity in rats. Br J Pharmacol 129(2):231–234 Vestergaard M, Ingmer H (2019) Antibacterial and antifungal properties of resveratrol. Int J Antimicrob Agents 53(6):716–723 Vijayakumar MR, Kumari L, Patel KK, Vuddanda PR, Vajanthri KY, Mahto SK, Singh S (2016) Intravenous administration of trans-resveratrol-loaded TPGS-coated solid lipid nanoparticles for prolonged systemic circulation, passive brain targeting and improved in vitro cytotoxicity against C6 glioma cell lines. RSC Adv 6(55):50336–50348 Walle T (2011) Bioavailability of resveratrol. Ann N Y Acad Sci 1215(1):9–15. https://doi.org/10.1111/j.1749-6632.2010.05842.x Wang Z-Y (2001) Arsenic compounds as anticancer agents. Cancer Chemother Pharmacol 48(1):S72–S76 Widemann BC, Adamson PC (2006) Understanding and managing methotrexate nephrotoxicity. Oncologist 11(6):694–703 Wiederrecht G, Lam E, Hung S, Martin M, Sigal N (1993) The mechanism of action of FK-506 and cyclosporin A. Ann N Y Acad Sci 696(1):9–19 Xia N, Strand S, Schlufter F, Siuda D, Reifenberg G, Kleinert H, Li H (2013) Role of SIRT1 and FOXO factors in eNOS transcriptional activation by resveratrol. Nitric Oxide 32:29–35 Xiao Z, Chen C, Meng T, Zhang W, Zhou Q (2016) Resveratrol attenuates renal injury and fibrosis by inhibiting transforming growth factor-β pathway on matrix metalloproteinase 7. Exp Biol Med 241(2):140–146 Xu S, Gao Y, Zhang Q, Wei S, Chen Z, Dai X, Zhao K-S (2016) SIRT1/3 activation by resveratrol attenuates acute kidney injury in a septic rat model. Oxid Med Cell Longev. https://doi.org/10.1155/2016/7296092 Xue H-Y, Yuan L, Cao Y-J, Fan Y-P, Chen X-L, Huang X-Z (2016) Resveratrol ameliorates renal injury in spontaneously hypertensive rats by inhibiting renal micro-inflammation. Biosci Rep. https://doi.org/10.1042/BSR20160035 Yu M, Xue J, Li Y, Zhang W, Ma D, Liu L, Zhang Z (2013) Resveratrol protects against arsenic trioxide-induced nephrotoxicity by facilitating arsenic metabolism and decreasing oxidative stress. Arch Toxicol 87(6):1025–1035 Zhang J, Tian Q, Zhou S-F (2006) Clinical pharmacology of cyclophosphamide and ifosfamide. Curr Drug Ther 1(1):55–84 Zhang W, Liu Y, Ge M, Jing J, Chen Y, Jiang H, Zhang Z (2014) Protective effect of resveratrol on arsenic trioxide-induced nephrotoxicity in rats. Nutr Res Pract 8(2):220–226 Zhu Y, Fu J, Shurlknight KL, Soroka DN, Hu Y, Chen X, Sang S (2015) Novel resveratrol-based aspirin prodrugs: synthesis, metabolism, and anticancer activity. J Med Chem 58(16):6494–6506