RESVERATROL ATTENUATES OXIDATIVE STRESS IN CHEMOTHERAPY INDUCED ACUTE KIDNEY INJURY: AN EXPERIMENTAL RAT MODEL
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Abstract
OBJECTIVE: To investigate the anti-oxidative and anti-nephrotoxic effects of Resveratrol in cisplatin induced nephrotoxic albino Wistar rats.
METHODS: This quasi-experimental study was performed at Isra University, Hyderabad, Pakistan. Thirty male albino Wistar rats were divided into three groups: group-A (control), group-B (cisplatin) and group-C (cisplatin+Resveratrol). Biochemical [serum urea, creatinine and glutathione peroxidase (GPX)] and renal histomorphology was performed in all groups after 21 days of treatment.
RESULTS: Difference in mean pre- and post-experimental body weight was observed in all three groups. Mean body weight decreased from 241.7±8.5 gm to 196.50±9.34 gm and from 237±7.4 gm to 207.2±6.56 gm in group-B and group-C respectively. In group-A; mean serum urea was 22.7±2.66 mg/dl, serum creatinine was 0.45±0.05 mg/dl and serum GPX was 1.44±0.13 ηg/ml. In group-B; mean serum urea level was 51±3.65 mg/dl, mean serum creatinine was 0.78±0.05 mg/dl and serum GPX was 0.85±0.11 ηg/ml. In group-C, mean serum urea level was 32.8±1.45 mg/dl, serum creatinine level was 0.41±0.09 mg/dl and serum GPX was 1.53±0.08 ηg/ml. In group-A, renal structure was intact, marked changes were observed in renal histology of group-B while group-C displayed less glomerular damage. The mean distance between visceral and parietal layers of Bowman’s capsule was 69.34±0.87 µm in group-A, 216.5±1.32 µm in group-B while 102.22±1.65 µm in group-C. Areas of peritubular fibrosis and congestion were observed in groups B and C but less prominent in group-C compared with group-B.
CONCLUSION: Resveratrol therapy is a potent anti-nephrotoxic regime showing promising results in chemotherapy induced nephrotoxicity and oxidative stress.
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References
Bellomo R. Acute Dialysis Quality Initiative workgroup. Acute renal failure-definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004;8:R204-12. DOI: 10.1186/cc2872
Linkermann A, Chen G, Dong G, Kunzendorf U, Krautwald S, Dong Z. Regulated cell death in AKI. Clin J Am Soc Nephrol 2014 1;25(12):2689-701. DOI: 10.1681/ASN.2014030262
Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet 2012 31;380(9843):756-66. DOI: 10.1016/S0140-6736(11)61454-2
Hsu CY, McCullough CE, Fan D, Ordonez JD, Cherow GM, Go AS. Community-based incidence of acute renal failure. Kidney Int 2007;72(2):208–12. DOI: 10.1038/sj.ki.5002297
Liangos O, Wald R, O’Bell JW, Price L, Pereira BJ, Jaber BL. Epidemiology and outcomes of acute renal failure in hospitalized patients: a national survey. Clin J Am Soc Nephrol 2006;1(1):43–51. DOI: 10.2215/CJN.00220605
Bagshaw SM, George C, Bellomo R, and the ANZICS Database Management Committee. Early acute kidney injury and sepsis: a multicentre evaluation. Crit Care 2008; 12(2): R47. DOI: 10.1186/cc6863
Hoste EA, Clermont G, Kersten A, Venkataraman R, Angus DC, De Bacquer D, et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care 2006;10(3):R73. DOI: 10.1186/cc4915
Khan FG, Ahmed E. Acute renal failure in diabetes mellitus. J Pak Med Assoc 2015 Feb;65(2):179-82.
Pannu N, Nadim MK. An overview of drug-induced acute kidney injury. Crit Care Med 2008 Apr 1;36(4):S216-23. DOI: 10.1097/ccm.0b013e318168e375
Karimi G, Khoei A, Omidi A, Kalantari M, Babaei J, Taghiabadi E, et al. Protective effect of aqueous and ethanolic extracts of Portulaca oleracea against cisplatin induced nephrotoxicity. Iran J Basic Med Sci 2010 Apr 1;13(2):31-5. DOI: 10.22038/IJBMS.2010.5079
Yu W, Chen Y, Dubrulle J, Stossi F, Putluri V, Sreekumar A, et al. Cisplatin generates oxidative stress which is accompanied by rapid shifts in central carbon metabolism. Sci Rep 2018 Mar 9;8(1):4306. DOI: 10.1038/s41598-018-22640-y
Sharma M, Gupta YK. Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats. Life Sci 2002 11;71(21):2489-98. DOI: 10.1016/S0024-3205(02)02083-0
Malhotra A, Bath S, Elbarbry F. An organ system approach to explore the antioxidative, anti-inflammatory, and cytoprotective actions of resveratrol. Oxid Med Cell Longev 2015;2015:803971. DOI: 10.1155/2015/803971
Al Dera HS. Protective effect of resveratrol against aluminum chloride induced nephrotoxicity in rats. Saudi Med J 2016;37(4):369. DOI: 10.15537/smj.2016.4.13611
Li H, Xia N, Förstermann U. Cardiovascular effects and molecular targets of resveratrol. Nitric Oxide 2012 Feb 15;26(2):102-10. DOI: 10.1016/j.niox.2011.12.006
Kitada M, Koya D. Renal protective effects of resveratrol. Oxid Med Cell Longev 2013;2013:568093. DOI: 10.1155/2013/568093
Sahu BD, Kumar JM, Sistla R. Baicalein, a bioflavonoid, prevents cisplatin-induced acute kidney injury by up-regulating antioxidant defenses and down-regulating the MAPKs and NF-κB pathways. PLoS One. 2015 Jul 29;10(7):e0134139. DOI: 10.1371/journal.pone.0134139
Ghosh J, Das J, Manna P, Sil PC. Acetaminophen induced renal injury via oxidative stress and TNF-alpha production: therapeutic potential of arjunolic acid. Toxicology 2010; 268: 8-18. DOI: 10.1016/j.tox.2009.11.011
Osman AM, Telity SA, Damanhouri ZA, Al-Harthy SE, Al-Kreathy HM, Ramadan WS, et al. Chemosensitizing and nephroprotective effect of resveratrol in cisplatin–treated animals. Cancer Cell Int 2015 Dec;15(1):6. DOI: 10.1186/s12935-014-0152-2
Sharma S, Anjaneyulu M, Kulkarni SK, Chopra K. Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats. Pharmacology 2006;76(2):69-75. DOI: 10.1159/000089720
Holthoff JH, Wang Z, Seely KA, Gokden N, Mayeux PR. Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury. Kidney Int 2012 Feb 2;81(4):370-8. DOI: 10.1038/ki.2011.347
Şener G, Tuğtepe H, Yüksel M, Çetinel Ş, Gedik N, Yeğen BÇ. Resveratrol improves ischemia/reperfusion-induced oxidative renal injury in rats. Arch Med Res 2006;37(7):822-9. DOI: 10.1016/j.arcmed.2006.04.003
Leonard SS, Xia C, Jiang BH, Stinefelt B, Klandorf H, Harris GK, et al. Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem Biophys Res Commun 2003;309(4):1017-26. DOI: 10.1016/j.bbrc.2003.08.105
Chen KH, Hung CC, Hsu HH, Jing YH, Yang CW, Chen JK. Resveratrol ameliorates early diabetic nephropathy associated with suppression of augmented TGF-β/smad and ERK1/2 signaling in streptozotocin-induced diabetic rats. Chem Biol Interact 2011;190(1):45-53. DOI: 10.1016/j.cbi.2011.01.033
Wu L, Zhang Y, Ma X, Zhang N, Qin G. The effect of Resveratrol on FoxO1 expression in kidneys of diabetic nephropathy rats. Mol Biol Rep 2012;39(9):9085-93. DOI: 10.1007/s11033-012-1780-z