Environmental Science and Pollution Research

, Volume 25, Issue 16, pp 15785–15792 | Cite as

Protective effect of grape or apple juices in bone tissue of rats exposed to cadmium: role of RUNX-2 and RANK/L expression

  • Pedro Luiz Menin Ruiz
  • Bianca Andrade Handan
  • Carolina Foot Gomes de Moura
  • Livia Ribeiro Assis
  • Kelly Rossetti Fernandes
  • Ana Claudia Muniz Renno
  • Daniel Araki Ribeiro
Research Article


The aim of this study was to investigate if grape or apple juices are able to protect bone tissue of rats exposed to cadmium. For this purpose, histopathological analysis and immunohistochemistry for RUNX-2 and RANK-L were investigated in this setting. A total of 20 adult Wistar rats were distributed into four groups (n = 5), as follows: control group, cadmium group, cadmium and grape juice group, and Cadmium and apple juice group. Control group received a single intraperitoneal (i.p.) water injection. Cadmium group received a single i.p. injection of cadmium chloride (1.2 mg/kg body weight) diluted in water. Cadmium and grape juice and cadmium and apple juice groups received a single i.p. injection of cadmium chloride (1.2 mg/kg body), and after 15 days, the rats were treated with grape or apple juices for 15 days, by gavage. All animals were euthanized 30 days after the beginning of experiment. Histopathological analysis in rat femur revealed extensive bone loss in rats intoxicated with cadmium. Grape or apple juices were able to increase bone formation. Cadmium inhibited RUNX-2 immunoexpression whereas cadmium increased RANK-L immunoexpression in rat bone cells. Grape or apple juices increased RUNX-2 and decreased RANK-L immunoexpression after cadmium intoxication. Taken together, our results demonstrate that grape or apple juices are able to exert therapeutic activity following cadmium intoxication in rat bone tissue as result of stimulatory effect of bone formation by RUNX-2 upregulation and RANK-L downregulation.


Cadmium Rat Grape Apple Polyphenols Bone 



This study was supported by CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnológico) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior). Our thanks are extended to Golden Sucos (Farroupilha, RS, Brazil) for providing the grape or apple juices.

Compliance with ethical standards

Conflict of interest

The authors declared that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Pedro Luiz Menin Ruiz
    • 1
  • Bianca Andrade Handan
    • 1
  • Carolina Foot Gomes de Moura
    • 1
  • Livia Ribeiro Assis
    • 1
  • Kelly Rossetti Fernandes
    • 1
  • Ana Claudia Muniz Renno
    • 1
  • Daniel Araki Ribeiro
    • 1
  1. 1.Department of BiosciencesFederal University of Sao Paulo, UNIFESPSão PauloBrazil

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