Planta Med 2016; 82(07): 621-631
DOI: 10.1055/s-0042-103593
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

The Mechanism of the Osteoprotective Action of a Polyphenol-Rich Aronia melanocarpa Extract during Chronic Exposure to Cadmium is Mediated by the Oxidative Defense System

Malgorzata M. Brzóska
1   Department of Toxicology, Medical University of Bialystok, Bialystok, Poland
,
Joanna Rogalska
1   Department of Toxicology, Medical University of Bialystok, Bialystok, Poland
,
Alicja Roszczenko
1   Department of Toxicology, Medical University of Bialystok, Bialystok, Poland
,
Malgorzata Galazyn-Sidorczuk
1   Department of Toxicology, Medical University of Bialystok, Bialystok, Poland
,
Michal Tomczyk
2   Department of Pharmacognosy, Medical University of Bialystok, Bialystok, Poland
› Author Affiliations
Further Information

Publication History

received 14 September 2015
revised 09 February 2016

accepted 12 February 2016

Publication Date:
20 April 2016 (online)

Abstract

Recently, we demonstrated in a rat model that consumption of a polyphenol-rich extract obtained from the berries of Aronia melanocarpa could protect from cadmium-induced disorders in bone turnover and changes in bone mineral status. The aim of this study was to investigate whether the osteoprotective effect of this extract is mediated by the oxidative defense system. Enzymatic and nonenzymatic antioxidants, total antioxidative and oxidative status, hydrogen peroxide, and markers of oxidative protein, lipid, and DNA damage were determined in bone tissue at the distal femoral epiphysis of female Wistar rats receiving 0.1 % aqueous A. melanocarpa extract (prepared from the lyophilized commercial extract containing 65.74 % of polyphenols) as the only drinking fluid and/or cadmium in the diet (1 and 5 mg/kg) for 3, 10, 17, and 24 months. The total oxidative and antioxidative status of the serum was also evaluated. The administration of A. melanocarpa extract provided significant protection from cadmium-induced oxidative stress in the bone and serum, and from lipid peroxidation and oxidative damage to the protein and DNA in the bone tissue. Numerous correlations were noted between indices of the oxidative/antioxidative bone status and markers of bone metabolism previously assayed in the animals receiving A. melanocarpa extract. The results allow the conclusion that the ability of A. melanocarpa extract to mediate the oxidative defense system and prevent oxidative modifications of protein, lipid, and DNA in the bone tissue plays an important role in its osteoprotective action under exposure to cadmium. The findings provide further evidence supporting our suggestion that chokeberry may be a promising natural agent for protection against the toxic action of cadmium in women chronically exposed to this metal.

Supporting Information

 
  • References

  • 1 Satarug S, Garrett SH, Sens MA, Sens DA. Cadmium, environmental exposure, and health outcomes. Environ Health Perspect 2010; 118: 182-190
  • 2 Nawrot TS, Staessen JA, Roels HA, Munters E, Cuypers A, Richart T, Ruttens A, Smeets K, Clijsters H, Vangronsveld J. Cadmium exposure in the population: from health risks to strategies of prevention. Biometals 2010; 23: 769-782
  • 3 Prabu MS, Shagirtha K, Renugadevi J. Naringenin in combination with vitamins C and E potentially protects oxidative stress-mediated hepatic injury in cadmium-intoxicated rats. J Nutr Sci Vitaminol 2011; 57: 177-185
  • 4 Flora SJS, Shrivastava R, Mittal M. Chemistry and pharmacological properties of some natural and synthetic antioxidants for heavy metal toxicity. Curr Med Chem 2013; 20: 4540-4574
  • 5 Bashir N, Manoharan V, Prabu MS. Protective role of grape seed proanthocyanidins against cadmium induced hepatic dysfunction in rats. Toxicol Res 2014; 3: 131-141
  • 6 Brzóska MM, Borowska S, Tomczyk M. Antioxidants as a potential preventive and therapeutic strategy for cadmium. Curr Drug Targets advance online publication 6 May 2015 DOI: 10.2174/1389450116666150506114336.
  • 7 García-Niňo WR, Pedraza-Chaverrí J. Protective effect of curcumin against heavy metals-induced liver damage. Food Chem Toxicol 2014; 69: 182-201
  • 8 Pari L, Shagirtha K. Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats. Exp Toxicol Pathol 2012; 64: 513-520
  • 9 Renugadevi J, Prabu MS. Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin. Exp Toxicol Pathol 2010; 62: 171-181
  • 10 Åkesson A, Barregard L, Bergdahl IA, Nordberg GF, Nordberg M, Skerfving S. Non-renal effects and the risk assessment of environmental cadmium exposure. Environ Health Perspect 2014; 122: 431-438
  • 11 Chen X, Gan C, Zhu G, Jin T. Benchmark dose for estimation of cadmium reference level for osteoporosis in a Chinese female population. Food Chem Toxicol 2013; 55: 592-595
  • 12 Sommar JN, Pettersson-Kymmer U, Lundh T, Svensson O, Hallmans G, Bergdahl IA. Hip fracture risk and cadmium in erythrocytes: a nested case-control study with prospectively collected samples. Calcif Tissue Int 2014; 94: 183-190
  • 13 Kokotkiewicz A, Jaremicz Z, Łuczkiewicz M. Aronia plants: a review of traditional use, biological activities, and perspectives for modern medicine. J Med Food 2010; 13: 255-269
  • 14 Kulling SE, Rawel HM. Chokeberry (Aronia melanocarpa) – A review on the characteristic components and potential health effects. Planta Med 2008; 74: 1625-1634
  • 15 Kowalczyk E, Kopff A, Fijalkowski P, Kopff M, Niedworok J, Blaszczyk J, Kędziora J, Tyslerewicz P. Effect of anthocyanins on selected biochemical parameters in rats exposed to cadmium. Acta Biochim Pol 2003; 50: 543-548
  • 16 Choi JH, Rhee IK, Park KY, Park KY, Kim JK, Rhee SJ. Action of green tea catechin on bone metabolic disorder in chronic cadmium-poisoned rats. Life Sci 2003; 73: 1479-1489
  • 17 Paik MK, Lee HO, Chung HS, Yang SO, Kim JH, Om AS. Genistein may prevent cadmium-induced bone loss in ovariectomized rats. J Med Food 2003; 6: 337-343
  • 18 Denev PN, Kratchanov CG, Ciz M, Lojek A, Kratchanova MG. Bioavailability and antioxidant activity of black chokeberry (Aronia melanocarpa) polyphenols: in vitro and in vivo evidences and possible mechanisms of action: a review. Compr Rev Food Sci Food Saf 2012; 11: 471-489
  • 19 Olas B, Wachowicz B, Nowak P, Kedzierska M, Tomczak A, Stochmal A, Oleszek W, Jeziorski A, Piekarski J. Studies on antioxidant properties of polyphenol-rich extract from berries of Aronia melanocarpa in blood platelets. J Physiol Pharmacol 2008; 59: 823-835
  • 20 Bräunlich M, Slimestad R, Wangensteen H, Brede C, Malterud KE, Barsett H. Extracts, anthocyanins and procyanidins from Aronia melanocarpa as radical scavengers and enzyme inhibitors. Nutrients 2013; 5: 663-678
  • 21 Hubert PA, Lee SG, Lee SK, Chun OK. Dietary polyphenols, berries, and age-related bone loss: a review based on human, animal, and cell studies. Antioxidants 2014; 3: 144-158
  • 22 Brzóska MM, Galazyn-Sidorczuk M, Jurczuk M, Tomczyk M. Protective effect of Aronia melanocarpa polyphenols on cadmium accumulation in the body: a study in a rat model of human exposure to this metal. Curr Drug Targets 2015; 16: 1470-1487
  • 23 Brzóska MM, Rogalska J, Galażyn-Sidorczuk M, Jurczuk M, Roszczenko A, Tomczyk M. Protective effect of Aronia melanocarpa polyphenols against cadmium-induced disorders in bone metabolism: a study in a rat model of lifetime human exposure to this heavy metal. Chem Biol Interact 2015; 229: 132-146
  • 24 Brzóska MM, Rogalska J, Kupraszewicz E. The involvement of oxidative stress in the mechanisms of damaging cadmium action in bone tissue: a study in a rat model of moderate and relatively high human exposure. Toxicol Appl Pharmacol 2011; 250: 327-335
  • 25 Wauquier F, Leotoing L, Coxam V, Guicheux J, Wittrant Y. Oxidative stress in bone remodelling and disease. Trends Mol Med 2009; 15: 468-477
  • 26 Smith SS, Reyes JR, Arbon KS, Harvey WA, Hunt LM, Heggland SJ. Cadmium-induced decrease in RUNX2 mRNA expression and recovery by the antioxidant N-acetylcysteine (NAC) in the human osteoblast-like cell line, Saos-2. Toxicol In Vitro 2009; 23: 60-66
  • 27 Brzóska MM, Rogalska J. Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats. Toxicol Appl Pharmacol 2013; 272: 208-220
  • 28 Matović V, Buha A, Ðukić-Ćosić D, Bulat Z. Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys. Food Chem Toxicol 2015; 78: 130-140
  • 29 Dai F, Chen WF, Zhou B. Antioxidant synergism of green tea polyphenols with alpha-tocopherol and L-ascorbic acid in SDS micelles. Biochimie 2008; 90: 1499-1505
  • 30 Graversen HB, Becker EM, Skibsted LH, Andersen ML. Antioxidant synergism between fruit juice and α-tocopherol. A comparison between high phenolic black chokeberry (Aronia melanocarpa) and high ascorbic blackcurrant (Ribes nigrum). Eur Food Res Technol 2008; 226: 737-743
  • 31 Kwak SC, Lee C, Kim JY, Oh HM, So HS, Lee MS, Rho MC, Oh J. Chlorogenic acid inhibits osteoclast differentiation and bone resorption by down-regulation of receptor activator of nuclear factor kappa-B ligand-induced nuclear factor of activated T cells c1 expression. Biol Pharm Bull 2013; 36: 1779-1786
  • 32 Derakhshanian H, Djalali M, Djazayery A, Nourijelyani K, Ghadbeigi S, Pishva H, Saedisomeolia A, Bahremand A, Dehpour AR. Quercetin prevents experimental glucocorticoid-induced osteoporosis: a comparative study with alendronate. Can J Physiol Pharmacol 2013; 91: 380-385
  • 33 Yamaguchi M, Weitzmann MN. Zinc stimulates osteoblastogenesis and suppresses osteoclastogenesis by antagonizing NF-κB activation. Mol Cell Biochem 2011; 355: 179-186
  • 34 Hadley KB, Newman SM, Hunt JR. Dietary zinc reduces osteoclast resorption activities and increases markers of osteoblast differentiation, matrix maturation, and mineralization in the long bones of growing rats. J Nutr Biochem 2010; 21: 297-303
  • 35 Sanchez C, Horcajada MN, Membrez Scalfo F, Ameye L, Offord E, Henrotin Y. Carnosol inhibits pro-inflammatory and catabolic mediators of cartilage breakdown in human osteoarthritic chondrocytes and mediates cross-talk between subchondral bone osteoblasts and chondrocytes. PLoS One 2015; 10: e0136118
  • 36 Bhattacharyya MH. Cadmium osteotoxicity in experimental animals: mechanisms and relationship to human exposure. Toxicol Appl Pharmacol 2009; 238: 258-265
  • 37 Kirakosyan A, Seymour EM, Wolforth J, McNish R, Kaufman PB, Bolling SF. Tissue bioavailability of anthocyanins from whole tart cherry in healthy rats. Food Chem 2015; 171: 26-31
  • 38 Vahter M, Akesson A, Lidén C, Ceccatelli S, Berglund M. Gender differences in the disposition and toxicity of metals. Environ Res 2007; 104: 85-95
  • 39 Brzóska MM, Moniuszko-Jakoniuk J. Bone metabolism of male rats chronically exposed to cadmium. Toxicol Appl Pharmacol 2005; 207: 195-211
  • 40 Brzóska MM, Moniuszko-Jakoniuk J. Disorders in bone metabolism of female rats chronically exposed to cadmium. Toxicol Appl Pharmacol 2005; 202: 68-83
  • 41 Hellström JK, Shikov AN, Makarova MN, Pihlanto AM, Pozharitskaya ON, Ryhänen EL, Kivijärvi P, Makarov VG, Mattila PH. Blood pressure-lowering properties of chokeberry (Aronia mitchurinii, var. Viking). J Funct Foods 2010; 2: 163-169
  • 42 Şahin E, Gümüşlü S. Immobilization stress in rat tissues: alterations in protein oxidation, lipid peroxidation and antioxidant defense system. Comp Biochem Physiol C Toxicol Pharmacol 2007; 144: 342-347
  • 43 Aebi HE. Catalase in vitro . Methods Enzymol 1984; 105: 121-126
  • 44 Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959; 82: 70-77
  • 45 Reznick AZ, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 1994; 233: 357-363