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 Oct 1;272(1):208-20. doi: 10.1016/j.taap.2013.05.016. Epub 2013 May 30.


It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/antioxidative status, and Cd and Zn were determined in the distal femur of the rats administered Zn (30 and 60mg/l) or/and Cd (5 and 50mg/l) for 6months. Soluble RANKL (sRANKL) and OPG were measured in the bone and serum. Zn supplementation importantly protected from Cd-induced oxidative stress preventing protein, DNA, and lipid oxidation in the bone. Moreover, Zn protected from the Cd-induced increase in sRANKL concentration and the sRANKL/OPG ratio, and decrease in OPG concentration in the bone and serum. Numerous correlations were noted between indices of the oxidative/antioxidative bone status, concentrations of sRANKL and OPG in the bone and serum, as well as the bone concentrations of Zn and Cd, and previously reported by us in these animals (Brzóska et al., 2007) indices of bone turnover and bone mineral density. The results allow us to conclude that the ability of Zn to prevent from oxidative stress and the RANK/RANKL/OPG system imbalance may be implicated in the mechanisms of its protective impact against Cd-induced bone damage. This paper is the first report from an in vivo study providing evidence that beneficial Zn impact on the skeleton under exposure to Cd is related to the improvement of the bone tissue oxidative/antioxidative status and mediating the RANK/RANKL/OPG system.

Keywords: 8-OHdG; 8-hydroxy-2′-deoxyguanosine; BMD; Bone tissue; CAT; CTX; Cadmium; Cd; Cu; Fe; GPx; GR; GSH; H(2)O(2); LPO; Mn; OC; OPG; OSI; Oxidative stress; P-SH; PC; Protection; RANK/RANKL/OPG system; ROS; SOD; T-SH; TAS; TOS; Zinc; Zn; bone mineral density; cadmium; carboxy-terminal cross-linking telopeptides of type I collagen; catalase; copper; glutathione peroxidase; glutathione reductase; hydrogen peroxide; iron; lipid peroxides; manganese; osteocalcin; osteoprotegerin; oxidative stress index; protein carbonyl groups; protein thiol groups; reactive oxygen species; reduced glutathione; sRANKL; sRANKL/OPG; soluble receptor activator of nuclear factor-κΒ; superoxide dismutase; the ratio of sRANKL and OPG; total antioxidative status; total oxidative status; total thiol groups; zinc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antioxidants / metabolism
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism*
  • Cadmium Chloride / toxicity*
  • Chlorides / pharmacology*
  • DNA Damage
  • Dietary Supplements*
  • Enzyme-Linked Immunosorbent Assay
  • Lipid Metabolism / drug effects
  • Male
  • NF-kappa B / metabolism*
  • Osteoprotegerin / metabolism*
  • Oxidative Stress / drug effects*
  • RANK Ligand / metabolism*
  • Rats
  • Rats, Wistar
  • Zinc Compounds / pharmacology*


  • Antioxidants
  • Chlorides
  • NF-kappa B
  • Osteoprotegerin
  • RANK Ligand
  • Zinc Compounds
  • zinc chloride
  • Cadmium Chloride