Elsevier

Chemico-Biological Interactions

Volume 229, 5 March 2015, Pages 132-146
Chemico-Biological Interactions

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

https://doi.org/10.1016/j.cbi.2015.01.031Get rights and content

Highlights

  • Low chronic exposure to cadmium (Cd) affects bone metabolism in female rats.

  • Aronia melanocarpa polyphenols (AMP) prevent Cd-induced disorders in bone turnover.

  • AMP improve the bone mineral status in Cd-exposed female rats.

  • AMP protect from low and moderate exposure to Cd-induced bone damage in female rats.

  • Chokeberry may be a promising preventive strategy for skeleton damage by Cd.

Abstract

It was investigated, in a female rat model of low and moderate lifetime human exposure to cadmium (Cd), whether polyphenols from Aronia melanocarpa berries (chokeberry; AMP) may offer protection from this heavy metal-induced disorders in bone metabolism. For this purpose, numerous indices of bone formation (osteocalcin, alkaline phosphatase, osteoprotegerin) and resorption (carboxy-terminal cross-linking telopeptides of type I collagen, soluble receptor activator of nuclear factor-κB ligand) in the serum and/or distal femur epiphysis (trabecular bone region), as well as bone mineral status (volumetric bone mineral density of the femur and content of mineral components, including calcium, in the bone tissue at the distal femur epiphysis) were evaluated in female Wistar rats that received a 0.1% aqueous extract of AMP, as the only drinking fluid (prepared from lyophilized extract by Adamed Consumer Healthcare), and/or Cd in diet (1 and 5 mg/kg) for 3, 10, 17, and 24 months. Examination of the phytochemical profile of the aronia extract revealed high content of polyphenols (612.40 ± 3.33 mg/g), including anthocyanins, proanthocyanidins, phenolic acids, and flavonoids. Among detected compounds anthocyanins were identified as dominating. The exposure to Cd, dose- and duration-dependently, enhanced resorption and inhibited formation of the bone tissue resulting in its decreased mineralization. The administration of AMP under the exposure to 1 and 5 mg Cd/kg diet provided important protection from this heavy metal-induced disturbances in the bone turnover and changes in the bone mineral status, and the beneficial impact of polyphenols resulted from their independent action and interaction with Cd. These findings suggest that consumption of Aronia melanocarpa polyphenols may play a role in prevention against female skeleton damage due to chronic exposure to Cd and that chokeberry represents the good natural plant candidate for further investigations of its prophylactic use under environmental exposure to this heavy metal.

Introduction

Recently, due to the common exposure of the general population to numerous xenobiotics, including toxic heavy metals, more and more attention has been focused on the possibility of using of natural plant ingredients in protection against the unfavorable health effects of their action [1], [2], [3]. A promising group of such compounds seem to be polyphenols being the most abundant bioactive compounds in plants. Some experimental data indicates that polyphenolic compounds may play a role in protection from the toxic action of heavy metals, including cadmium (Cd), but the data are sparse [2], [4], [5], [6].

Cd belongs to the group of xenobiotics to which humans are exposed throughout their lifetime [7], [8]. Numerous data show that under chronic exposure to this heavy metal, bone (besides the kidneys) is a target organ for its toxicity [9], [10], [11], [12], [13], [14], [15], [16]. A growing body of epidemiological studies provides evidence that even relatively low chronic exposure to Cd, nowadays taking place in industrialized countries, may contribute to the development of osteoporosis and bone fractures [14], [15], [16]. This, together with the forecast that the general population’s exposure to this metal will increase [7], [8], makes the search for effective ways of protection from the unfavorable effects of its action, including skeleton damage, necessary.

Polyphenols occur naturally in plant-derived food, and are present in commonly consumed fruits, vegetables, grains, herbs, and drinks such as tea (especially green and white tea), fruit and/or vegetable juices, and wine [17]. These compounds possess numerous biological activities, including mainly antioxidative, anti-carcinogenic, anti-inflammatory, antiviral, and anti-hypertensive action [17], [18]. Polyphenolic compounds are also known to have osteo-protective action in human and experimental animals; however, most of the data refer to green tea and soybeans polyphenols [19], [20], [21].

Some literature data [4], [5], [6] and our recent findings [22], [23] suggest that polyphenols possess the potential to protect against Cd accumulation in the body and its toxicity. Due to the presence of hydroxyl groups (single bondOH groups), these compounds are capable of chelating ions of metals, including Cd2+ ions (Fig. 1) [24], [25], [26]. Choi et al. [4] reported that catechin (present in great amounts in green tea) was capable of providing protection from bone damage due to relatively high Cd exposure, while Paik et al. [6] revealed the beneficial impact of genistein (isoflavone occurring in soybeans) on the skeleton of Cd-exposed ovariectomized rats. Recently, using a rat model of low and moderate lifetime human exposure to this metal (1 and 5 mg Cd/kg diet, respectively, for up to 24 months), we revealed that polyphenols from the berries of Aronia melanocarpa (chokeberry, [Michx.] Elliott, Rosaceae; AMP) may decrease gastrointestinal absorption and body burden of this xenobiotic, including its accumulation in the liver, kidney and bone tissue (Table 1) ([22], [23], submitted for publication).

Nowadays, consumption of aronia berries is widely recommended as one of the most abundant sources of polyphenols [27], [28], [29]. The polyphenolic profile of Aronia melanocarpa berries is well-known and widely reported [27], [28], [29], [30]. Anthocyanins (mainly cyanidin 3-O-α-arabinoside – Cy-3-ara, cyanidin 3-O-β-galactoside – Cy-3-gal, cyanidin 3-O-β-glucoside – Cy-3-glu, and cyanidin-3-xyloside, and relatively low amounts of pelargonidin-3-galactoside and pelargonidin-3-arabinoside), proanthocyanidins (oligomeric and polymeric catechins), flavonols (quercetin, kaempferol and several quercetin mono- and di-glycosides: quercetin-3-galactoside, quercetin-3-glucoside, quercetin-3-rutinoside, quercetin-3-vicianoside, and quercetin-3-robinobioside), and hydroxycinnamic acids (chlorogenic acid – CA and neochlorogenic acid) are present in the extract.

To our knowledge, the impact of AMP on bone metabolism has not been investigated so far; however, some subclasses of polyphenolic compounds present in chokeberries (anthocyanins, phenolic acids, flavonols) have been reported to have a favorable impact on bone metabolism [21], [31], [32]. Taking the above into account, including our own finding of decreased Cd concentration in the bone tissue due to AMP administration under moderate exposure to this metal (Table 1), we have hypothesized that consumption of these compounds under exposure to Cd may, at least partly, provide protection from its damaging impact on the skeleton. The present paper is the first report from our comprehensive study on this subject, and it was aimed at investigating whether AMP consumption under low and moderate chronic exposure to Cd may protect from disorders in bone metabolism. For this purpose, the influence of AMP on the bone turnover and bone mineral status was evaluated in the experimental model of low and moderate lifetime human exposure to Cd, in which we have revealed the protective impact of these compounds regarding the body burden of this metal. The possibility of using A. melanocarpa berries in protection against this heavy metal-caused skeleton damage has not been a subject of interest until now, and this work provides new and important data in this field.

Section snippets

Chemicals and reagents

All the chemicals and reagents used were of the highest-grade purity or analytical purity. Cadmium chloride (CdCl2 × 2½ H2O), sodium chloride (NaCl), disodium carbonate, potassium dihydrogen phosphate, and dipotassium hydrogen phosphate were purchased from POCh (Gliwice, Poland). Morbital and heparin were received from Biowet (Pulawy, Poland) and Biochemie GmbH (Kundl, Austria), respectively. Folin–Ciocalteu’s phenol reagent and gallic acid (a standard) used in total polyphenols determination

Polyphenolic profile of the AMP extract

The UPLC separation of the AMP extract revealed a number of peaks in the 245 nm profile (Fig. 2). Two peaks corresponding to phenolic acids (neochlorogenic acid and CA), six peaks corresponding to anthocyanins (including Cy-3-gal, Cy-3-glu, and Cy-3-ara) and seven peaks corresponding to flavonols derivatives (quercetin) were identified (Fig. 2).

High concentrations of polyphenols, including anthocyanins, proanthocyanidins, phenolic acids, and flavonoids were determined in the aronia extract (

Discussion

The present paper is the first to investigate and reveal protective impact of AMP on bone metabolism under Cd exposure, and is one of very few reports [4], [6] on the beneficial effect of polyphenols regarding this metal-caused changes in the skeleton. The important finding of this study is also revealing that Cd creates a risk to bone health at lower exposure than was previously reported by us [9], [10]. In the available literature there is still no another experimental data on the impact on

Conflict of Interest

The authors declare that there are no conflicts of interest.

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Acknowledgements

This work was supported by the Grant (No. N N405 051140) from Narodowe Centrum Nauki (Poland). The study was conducted with the use of equipment by the Medical University of Bialystok (Poland) as part of the OP DEP 2007-2013, Priority Axis I.3, contract No. POPW.01.00-20-001/12.

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