Comparison of the effect of beta-alanyl-L-histidinato zinc and its zinc-chelating ligand on bone metabolism in tissue culture

Biol Pharm Bull. 1994 Apr;17(4):522-6. doi: 10.1248/bpb.17.522.


The present investigation was undertaken to compare the effects of beta-alanyl-L-histidinato zinc (AHZ) and its zinc-chelating ligands on bone metabolism in tissue culture. Calvaria were removed from 3-week-old male rats and cultured for up to 72 h in Dulbecco's modified eagle medium containing zinc sulfate, AHZ, di(N-acetyl-beta-alanyl-L-histidinato)zinc (AAHZ), and di(histidino)zinc (HZ). The bone calcium content and alkaline phosphatase activity were significantly increased in the presence of AHZ or AAHZ (10(-8)-10(-5) M). Those increases were seen at 10(-7) to 10(-5) M zinc sulfate and HZ. The bone deoxyribonucleic acid (DNA) content was significantly increased by AHZ or AAHZ with 10(-7) to 10(-5) M, while 10(-7) M zinc sulfate and HZ had no effect. Thus, AHZ and AAHZ had more potent effect than that of zinc sulfate and HZ. The effect of AHZ, AAHZ and HZ (10(-5) M) increasing bone alkaline phosphatase activity was abolished by the presence of 10(-4) M dipicolinate, a chelator of zinc. Moreover, the effect of these zinc compounds on bone metabolic indices was not seen in the presence of 10(-6) M cycloheximide. The present results suggest that the effect of AHZ and AAHZ on bone metabolism is more potent than that of zinc sulfate and HZ.

Publication types

  • Comparative Study

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism*
  • Calcium / metabolism
  • Carnosine* / analogs & derivatives*
  • Chelating Agents / pharmacology
  • Culture Techniques
  • Cycloheximide / pharmacology
  • DNA / metabolism
  • Dipeptides / pharmacology*
  • Histidine / analogs & derivatives
  • Histidine / pharmacology
  • Male
  • Organometallic Compounds / pharmacology*
  • Rats
  • Zinc / pharmacology*
  • Zinc Compounds


  • Chelating Agents
  • Dipeptides
  • Organometallic Compounds
  • Zinc Compounds
  • di(N-acetylalanyl-histidinato)zinc
  • di(histidino)zinc
  • polaprezinc
  • Histidine
  • Carnosine
  • DNA
  • Cycloheximide
  • Alkaline Phosphatase
  • Zinc
  • Calcium