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The Antioxidant and Antigenotoxic Effects of Pycnogenol® on Rats Treated With Cisplatin

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Abstract

Oxidative stress and inflammation are implicated in the pathogenesis of cisplatin-induced toxicity. Pycnogenol® is known for its strong antioxidant and anti-inflammatory effects. In this study, the possible protective effects of pycnogenol on kidney, bone marrow, and red blood cells in rats treated with cisplatin were investigated. The rats were divided into four groups. Group 1 was the control and groups 2, 3, and 4 were orally treated with pycnogenol (200 mg/kg bw, o.p) for 5 days, treated with cisplatin (7 mg/kg bw, i.p.) on the fifth day and treated with cisplatin plus pycnogenol, respectively. Antioxidative parameters in kidney and red blood cells were measured. Chromosome anomalies in bone marrow and renal histopathology were also investigated. Activities of pro-oxidant enzymes (myeloperoxidase and xanthine oxidase), malondialdehyde, and nitric oxide levels significantly increased but antioxidant enzymes activities decreased in the kidneys and red blood cells after cisplatin treatment. Pycnogenol treatment prior to the administration of cisplatin significantly decreased cisplatin-induced injury, as evidenced by its normalizing these parameters. Chromosomal aberrations decreased and mitotic index frequencies increased in bone marrow treated with cisplatin plus pycnogenol. These findings suggest that pycnogenol may be a useful protective agent against the toxicity associated with cisplatin therapy.

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References

  1. Deorukhkar A, Krishnan S, Sethi G, Aggarwal BB (2007) Back to basics: how natural products can provide the basis for new therapeutics. Expert Opin Investig Drugs 16:1753–1773

    Article  PubMed  CAS  Google Scholar 

  2. Conklin KA (2004) Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integr Cancer Ther 3:294–300

    Article  PubMed  CAS  Google Scholar 

  3. Packer L, Rimbach G, Virgili F (1999) Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, pycnogenol. Free Radic Biol Med 27:704–724

    Article  PubMed  CAS  Google Scholar 

  4. Moini H, Guo Q, Packer L (2000) Enzyme inhibition and protein-binding action of the procyanidin-rich french maritime pine bark extract, pycnogenol: effect on xanthine oxidase. J Agric Food Chem 48:5630–5639

    Article  PubMed  CAS  Google Scholar 

  5. Saliou C, Rimbach G, Moini H, McLaughlin L, Hosseini S, Lee J, Watson R, Packer L (2001) Solar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract. Free Radical Biol Med 30:154–160

    Article  CAS  Google Scholar 

  6. Yao X, Panichpisal K, Kurtzman N, Nugent K (2007) Cisplatin nephrotoxicity: a review. Am J Med Sci 334(2):115–124

    Article  PubMed  Google Scholar 

  7. Gulec M, Iraz M, Yilmaz HR, Ozyurt H, Temel I (2006) The effects of ginkgo biloba extract on tissue adenosine deaminase, xanthine oxidase, myeloperoxidase, malondialdehyde, and nitric oxide in cisplatin-induced nephrotoxicity. Toxicol Ind Health 22:125–130

    Article  PubMed  CAS  Google Scholar 

  8. Yildirim Z, Sogut S, Odaci E, Iraz M, Ozyurt H, Kotuk M, Akyol O (2003) Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats. Pharmacol Res 47:49–56

    Article  Google Scholar 

  9. Evangelista CM, Antunes LM, Francescato HD, Bianchi M (2004) Effects of the olive, extra virgin olive and canola oils on cisplatin-induced clastogenesis in Wistar rats. Food Chem Toxicol 42:1291–1297

    Article  PubMed  CAS  Google Scholar 

  10. Sendao MC, Behling EB, dos Santos RA et al (2006) Comparative effects of acute and subacute lycopene administration on chromosomal aberrations induced by cisplatin in male rats. Food Chem Toxicol 44:1334–1339

    Article  PubMed  CAS  Google Scholar 

  11. Krizková L, Chovanová Z, Duracková Z, Krajcovic J (2008) Antigenotoxic in vitro activity of plant polyphenols: Pycnogenol® and Ginkgo biloba extract (EGb 761). Phytother Res 22:384–388

    Article  PubMed  Google Scholar 

  12. Kim YG, Park HY (2004) The effects of Pycnogenol on DNA damage in vitro and expression of superoxide dismutase and HP1 in Escherichia coli SOD and catalase deficient mutant cells. Phytother Res 18:900–905

    Article  PubMed  CAS  Google Scholar 

  13. Ulubaş B, Cimen MY, Apa DD, Saritaş E, Muşlu N, Cimen OB (2003) The protective effects of acetylsalicylic acid on free radical production in cisplatin induced nephrotoxicity: an experimental rat model. Drug Chem Toxicol 26(4):259–270

    Article  PubMed  Google Scholar 

  14. Ajith TA, Usha S, Nivitha V (2007) Ascorbic acid and alpha-tocopherol protect anticancer drug cisplatin induced nephrotoxicity in mice: a comparative study. Clin Chim Acta 375(1–2):82–86, Epub 2006 Jun 14

    Article  PubMed  CAS  Google Scholar 

  15. Cetin R, Devrim E, Kiliçoğlu B, Avci A, Candir O, Durak I (2006) Cisplatin impairs antioxidant system and causes oxidation in rat kidney tissues: possible protective roles of natural antioxidant foods. J Appl Toxicol 26(1):42–46

    Article  PubMed  CAS  Google Scholar 

  16. Feng WH, Wei HL, Liu GT (2002) Effect of PYCNOGENOL on the toxicity of heart, bone marrow and immune organs as induced by antitumor drugs. Phytomedicine 9(5):414–418

    Article  PubMed  CAS  Google Scholar 

  17. Kobuchi H, Virgili F, Packer L (1999) Assay of inducible form of nitric oxide synthase activity: effect of flavonoids and plant extracts. Methods Enzymol 301:504–513

    Article  PubMed  CAS  Google Scholar 

  18. Aebi H (1984) Catalase in vitro. Meth Enzymol 105:121–126

    Article  PubMed  CAS  Google Scholar 

  19. Winterbourn CC, Hawkins RE, Brian M, Carrell RW (1975) The estimation of red cell superoxide dismutase activity. J Lab Clin Med 85:337–341

    PubMed  CAS  Google Scholar 

  20. Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erytrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    PubMed  CAS  Google Scholar 

  21. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  22. Drabkin DL, Austin JH (1935) Spectrophotometric studies. II. Preparations from washed blood cells; nitric oxide hemoglobin and sulfhemoglobin. J Biol Chem 112:51–65

    CAS  Google Scholar 

  23. Parks DA, Williams TK, Beckman JS (1988) Conversion of xanthine dehydrogenase to oxidase in ischemic rat intestine: a reevaluation. Am Physiol Soc 254:G768–G774

    CAS  Google Scholar 

  24. Doganay S, Evereklioglu C, Er H, Türköz Y, Sevinç A, Mehmet N, Savli H (2002) Comparison of serum NO, TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels with grades of retinopathy in patients with diabetes mellitus. Eye 16:163–170

    Article  PubMed  CAS  Google Scholar 

  25. Moron MS, Depierre JW, Mannervik B (1979) Levels of GSH, GR and GST activities in rat lung and liver. Biochim Biophys Acta 582:67

    PubMed  CAS  Google Scholar 

  26. Bradley PP, Priebat DA, Christensen RD, Rothstein G (1982) Measurement of cutaneous inflammation, estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78:206–209

    Article  PubMed  CAS  Google Scholar 

  27. Esterbauer H, Chessman KH (1990) Determination of aldeydic lipid peroxidation products: malonaldeyde and 4-hydroxynonenal. Methods Enzymol 186:407–421

    Article  PubMed  CAS  Google Scholar 

  28. Preston RJ, Au W, Bender MA, Brewen JG, Carrano AV, Heddle JA, McFee AF, Wolff S, Wassom JS (1981) Mammalian in vivo and in vitro cytogenetic assays: a report of the U.S. EPA’s gene-tox programme. Mutat Res 87:143–188

    PubMed  CAS  Google Scholar 

  29. Savage JR (1976) Classification and relationships of induced chromosomal structural changes. J Med Genet 3:103–122

    Article  Google Scholar 

  30. Swierenga SH, Heddle JA, Sigal EA, Gilman JP, Brillinger RL, Douglas GR, Nestmann ER (1991) Recommended protocols based on a survey of current practice in genotoxicity testing laboratories, IV. Chromosome aberration and sister chromatid exchange in Chinese hamster ovary, V79 Chinese hamster lung and lymphocyte cultures. Mutat Res 246:301–322

    PubMed  CAS  Google Scholar 

  31. Maines MD (1986) Differential effect of cis-platinum (cis-diamminedichloroplatinum) on regulation of liver and kidney haem and haemoprotein metabolism. Possible involvement of gamma-glutamyl-cycle enzymes. Biochem J 237:713–721

    PubMed  CAS  Google Scholar 

  32. Dene BA, Maritim AC, Sanders RA, Watkins JB (2005) Effects of antioxidant treatment on normal and diabetic rat retinal enzyme activities. J Ocul Pharmacol Ther 21(1):28–35

    Article  PubMed  CAS  Google Scholar 

  33. Kim YJ, Kang KS, Yokozawa T (2008) The anti-melanogenic effect of pycnogenol by its anti-oxidative actions. Food Chem Toxicol 46(7):2466–2471

    Article  PubMed  CAS  Google Scholar 

  34. Kim J, Chehade J, Pinnas JL, Mooradian AD (2000) Effect of select antioxidants on malondialdehyde modification of proteins. Nutrition 16(11–12):1079–1081

    Article  PubMed  CAS  Google Scholar 

  35. Sivonová M, Waczulíková I, Kilanczyk E, Hrnciarová M, Bryszewska M, Klajnert B, Duracková Z (2004) The effect of pycnogenol on the erythrocyte membrane fluidity. Gen Physiol Biophys 23:39–51

    PubMed  Google Scholar 

  36. Pan H, Mukhopadhyay P, Rajesh M, Patel V, Mukhopadhyay B, Gao B, Haskó G, Pacher P (2009) Cannabidiol attenuates cisplatin-induced nephrotoxicity by decreasing oxidative/nitrosative stress, inflammation, and cell death. J Pharmacol Exp Ther 328(3):708–714

    Article  PubMed  CAS  Google Scholar 

  37. Chirino YI, Trujillo J, Sánchez-González DJ, Martínez-Martínez CM, Cruz C, Bobadilla NA, Pedraza-Chaverri J (2008) Selective iNOS inhibition reduces renal damage induced by cisplatin. Toxicol Lett 4(176(1)):48–57

    Article  Google Scholar 

  38. MacMillan-Crow LA, Crow JP, Kerby JD (1996) Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts. Proc Natl Acad Sci 93:11853–11858

    Article  PubMed  CAS  Google Scholar 

  39. Ramesh G, Reeves WB (2002) TNF-α mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. J Clin Invest 110:835–842

    PubMed  CAS  Google Scholar 

  40. Cho KJ, Yun CH, Yoon DY et al (2000) Effect of bioflavonoids extracted from the bark of Pinus maritima on proinflammatory cytokine interleukin-1 production in lipopolysaccharide-stimulated RAW 264.7. Toxicol Appl Pharmacol 168:64–71

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Birsen Aydin.

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Aydin, B., Unsal, M., Sekeroglu, Z.A. et al. The Antioxidant and Antigenotoxic Effects of Pycnogenol® on Rats Treated With Cisplatin. Biol Trace Elem Res 142, 638–650 (2011). https://doi.org/10.1007/s12011-010-8781-3

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  • DOI: https://doi.org/10.1007/s12011-010-8781-3

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