Hesperidin and Rutin, Antioxidant Citrus Flavonoids, Attenuate Cisplatin‐Induced Nephrotoxicity in Rats

This study aimed to assess the protective effect of hesperidin (HES) and rutin (RUT) against cisplatin‐induced nephrotoxicity in male rats. Cisplatin (5 mg/kg, intraperitoneal) caused significant increases in serum sodium, blood urea nitrogen, serum creatinine, total sodium and potassium excreted in urine, urine volume, and lipid peroxides measured as the malondialdehyde content of kidney, with significant decreases in serum total protein, creatinine clearance, reduced glutathione content of kidney, and kidney superoxide dismutase activity as compared with the control group. On the other hand, administration of HES (200 mg/kg, per oral [p.o.]) or RUT (30 mg/kg, p.o.) for 14 days with a single cisplatin dose on the tenth day ameliorated the cisplatin‐induced nephrotoxicity as indicated by the restoration of kidney function and oxidative stress biomarkers. Furthermore, the test drugs reduced the histopathological changes induced by cisplatin. In conclusion, HES and RUT showed protective effects against cisplatin‐induced nephrotoxicity.

[1]  Zhi-Zhong Yan,et al.  Protective effect of rutin on testicular ischemia-reperfusion injury. , 2011, Journal of pediatric surgery.

[2]  B. Geramizadeh,et al.  Effect of Simvastatin on Cisplatin-induced Nephrotoxicity in Male Rats , 2011 .

[3]  Shereen M. Refaie,et al.  Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice. , 2010, Toxicology.

[4]  E. Farombi,et al.  Phenolic extract of soybean (Glycine max) attenuates cisplatin-induced nephrotoxicity in rats. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[5]  A. Abdelrahman,et al.  N‐acetylcysteine improves renal hemodynamics in rats with cisplatin‐induced nephrotoxicity , 2010, Journal of applied toxicology : JAT.

[6]  E. Ramesh,et al.  Prevention of selenite-induced cataractogenesis by rutin in Wistar rats , 2009, Molecular vision.

[7]  A. Saad,et al.  Cisplatin induced damage in kidney genomic DNA and nephrotoxicity in male rats: the protective effect of grape seed proanthocyanidin extract. , 2009, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[8]  J. Pedraza-Chaverri,et al.  Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. , 2009, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[9]  Gwendolyn R. Goss,et al.  Theory and Practice of Histological Techniques , 2009 .

[10]  A. Nemmar,et al.  Ontogenic aspects of cisplatin-induced nephrotoxicity in rats. , 2008, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[11]  E. El-Sayed,et al.  Hesperidin, an antioxidant flavonoid, prevents acrylonitrile‐induced oxidative stress in rat brain , 2008, Journal of biochemical and molecular toxicology.

[12]  E. El-Sayed,et al.  Protective effect of captopril against cisplatin-induced nephrotoxicity in rats. , 2008, Pakistan journal of pharmaceutical sciences.

[13]  Z. Dong,et al.  Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. , 2008, Kidney international.

[14]  M. Mansouri,et al.  Protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rats. , 2008, Iranian biomedical journal.

[15]  J. Pedraza-Chaverri,et al.  Protective effects of apocynin against cisplatin-induced oxidative stress and nephrotoxicity. , 2008, Toxicology.

[16]  M. Mesić,et al.  Measurement of malondialdehyde (MDA) level in rat plasma after simvastatin treatment using two different analytical methods , 2008 .

[17]  V. Menon,et al.  Antioxidant properties of hesperidin in nicotine‐induced lung toxicity , 2007, Fundamental & clinical pharmacology.

[18]  A. Nemmar,et al.  The ameliorative effect of cysteine prodrug l‐2‐oxothiazolidine‐4‐carboxylic acid on cisplatin‐induced nephrotoxicity in rats , 2007, Fundamental & clinical pharmacology.

[19]  K. Nugent,et al.  Cisplatin Nephrotoxicity: A Review , 2007, The American journal of the medical sciences.

[20]  M. Dolan,et al.  Molecular mechanisms of resistance and toxicity associated with platinating agents. , 2007, Cancer treatment reviews.

[21]  K. Chopra,et al.  Beneficial effect of hesperidin on lipopolysaccharide-induced hepatotoxicity. , 2006, Toxicology.

[22]  I. Temel,et al.  The effects of ginkgo biloba extract on tissue adenosine deaminase, xanthine oxidase, myeloperoxidase, malondialdehyde, and nitric oxide in cisplatin-induced nephrotoxicity , 2006, Toxicology and industrial health.

[23]  K. Chopra,et al.  Renoprotective Effect of Spirulina fusiformis on Cisplatin-Induced Oxidative Stress and Renal Dysfunction in Rats , 2006, Renal failure.

[24]  E. Neuwelt,et al.  Protection against Cisplatin-Induced Toxicities by N-Acetylcysteine and Sodium Thiosulfate as Assessed at the Molecular, Cellular, and in Vivo Levels , 2005, Journal of Pharmacology and Experimental Therapeutics.

[25]  Wafaa A. Ahmed,et al.  Naringenin attenuates cisplatin nephrotoxicity in rats. , 2005, Life sciences.

[26]  K. Chopra,et al.  Hesperidin, a citrus bioflavonoid, decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney , 2005, BMC pharmacology.

[27]  A. Zwinderman,et al.  Supplementation with antioxidant micronutrients and chemotherapy-induced toxicity in cancer patients treated with cisplatin-based chemotherapy: a randomised, double-blind, placebo-controlled study. , 2004, European journal of cancer.

[28]  T. Boulikas,et al.  Cisplatin and platinum drugs at the molecular level. (Review). , 2003, Oncology reports.

[29]  G. Ramesh,et al.  TNFR2-mediated apoptosis and necrosis in cisplatin-induced acute renal failure. , 2003, American journal of physiology. Renal physiology.

[30]  H. Chung,et al.  Inhibitory activity of flavonoids fromPrunus davidiana and other flavonoids on total ROS and hydroxyl radical generation , 2003, Archives of pharmacal research.

[31]  T. Ninomiya,et al.  Antioxidant ameliorates cisplatin-induced renal tubular cell death through inhibition of death receptor-mediated pathways. , 2003, American journal of physiology. Renal physiology.

[32]  Anne M. Galea,et al.  The interaction of cisplatin and analogues with DNA in reconstituted chromatin. , 2002, Biochimica et biophysica acta.

[33]  R. Schrier Cancer therapy and renal injury. , 2002, The Journal of clinical investigation.

[34]  H. Hirakata,et al.  Protection by a radical scavenger edaravone against cisplatin-induced nephrotoxicity in rats. , 2002, European journal of pharmacology.

[35]  Kaixun Huang,et al.  Effects of rutin supplementation on antioxidant status and iron, copper, and zinc contents in mouse liver and brain , 2002, Biological Trace Element Research.

[36]  S. Garg,et al.  Chemistry and pharmacology of the citrus bioflavonoid hesperidin , 2001, Phytotherapy research : PTR.

[37]  U. Mohammed,et al.  Naturally occurring polyphenolic antioxidants modulate IgE‐mediated mast cell activation , 2000, Immunology.

[38]  T. A. Najjar,et al.  The effect of rebamipide on cisplatin-induced nephrotoxicity in rats. , 2000, Pharmacological research.

[39]  P. Pietta,et al.  Flavonoids as antioxidants. , 2000, Journal of natural products.

[40]  M. Malafa,et al.  Dose-dependent protection by lipoic acid against cisplatin-induced nephrotoxicity in rats: antioxidant defense system. , 2000, Pharmacology & toxicology.

[41]  D. Lebwohl,et al.  Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. , 1998, European journal of cancer.

[42]  C. Rice-Evans,et al.  The relative contributions of ascorbic acid and phenolic antioxidants to the total antioxidant activity of orange and apple fruit juices and blackcurrant drink , 1997 .

[43]  D. Erdinçler,et al.  Lipid peroxidation and antioxidant status in experimental animals: effects of aging and hypercholesterolemic diet. , 1997, Clinica chimica acta; international journal of clinical chemistry.

[44]  S. Toyokuni,et al.  Protection by αG‐Rutin, a Water‐soluble Antioxidant Flavonoid, against Renal Damage in Mice Treated with Ferric Nitrilotriacetate , 1997, Japanese journal of cancer research : Gann.

[45]  S. Karolczak,et al.  Evidence for antiradical and antioxidant properties of four biologically active N,N‐Diethylaminoethyl ethers of flavaone oximes: A comparison with natural polyphenolic flavonoid rutin action , 1997, Biochemistry and molecular biology international.

[46]  Andrew N. Rowan Guide for the Care and Use of Laboratory Animals , 1996 .

[47]  W. Regelson,et al.  Review of the biology of Quercetin and related bioflavonoids. , 1995, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[48]  M. Jones,et al.  L-methionine antagonism of cis-platinum nephrotoxicity. , 1990, Toxicology and applied pharmacology.

[49]  C. Fraga,et al.  Flavonoids as antioxidants evaluated by in vitro and in situ liver chemiluminescence. , 1987, Biochemical pharmacology.

[50]  S. Marklund,et al.  Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. , 1974, European journal of biochemistry.

[51]  E. Beutler,et al.  Improved method for the determination of blood glutathione. , 1963, The Journal of laboratory and clinical medicine.

[52]  Y. Yadav,et al.  NEPHROPHARMACOLOGICAL ACTIVITY OF ETHANOLIC EXTRACT LEPIDIUM SATIVUM L. SEEDS IN ALBINO RATS USING CISPLATIN INDUCED ACUTE RENAL FAILURE , 2010 .

[53]  R. Acquaviva,et al.  Bioflavonoids as antiradicals, antioxidants and DNA cleavage protectors , 2004, Cell Biology and Toxicology.

[54]  H. Arafa,et al.  Effect of Cremophor-EL on Cisplatin-Induced Organ Toxicity in Normal Rat , 2001 .

[55]  M. Lavrador,et al.  Effect of oral selenium administration on cisplatin-induced nephrotoxicity in rats. , 2001, Pharmacological research.

[56]  K. Winnefeld,et al.  Protective effects of vitamin E and C on cisplatin nephrotoxicity in developing rats , 1997, Archives of Toxicology.

[57]  L G Korkina,et al.  Antioxidant and chelating properties of flavonoids. , 1997, Advances in pharmacology.

[58]  P. Stricklett,et al.  Effect of reactive oxygen species on endothelin-1 production by human mesangial cells. , 1996, Kidney international.

[59]  K. Meyer,et al.  Cisplatin nephrotoxicity. , 1994, Mineral and electrolyte metabolism.

[60]  N. Wong,et al.  Mechanism of polyuria after cisplatin therapy. , 1993, Nephron.

[61]  G. Lopez-Berestein,et al.  Role of vascular congestion in cisplatin-induced acute renal failure in the rat. , 1992, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[62]  S. Aust,et al.  Microsomal lipid peroxidation. , 1978, Methods in enzymology.

[63]  W. Mommaerts [123] Ultraviolet circular dichroism in nucleic acid structural analysis , 1968 .