Inhibitory effect of beta-alanyl-L-histidinato zinc on bone resorption in tissue culture

Pharmacology. 1992;45(5):292-300. doi: 10.1159/000139013.


The inhibitory effect of beta-alanyl-L-histidinato zinc (AHZ) on bone resorption in tissue culture was investigated. Calvaria were removed from weanling rats (3-week-old male) and cultured for periods up to 48 h in Dulbecco's modified Eagle medium (high glucose, 4.5%) supplemented with antibiotics and bovine serum albumin. The experimental cultures contained 10(-7) to 10(-4) mol/l AHZ. The bone-resorbing factors, parathyroid hormone (1-34) (PTH; 10(-7) mol/l), prostaglandin E2 (10(-5) mol/l), interleukin-1 alpha (IL1 alpha; 50 U/ml), and lipopolysaccharide (10 micrograms/ml), caused a significant decrease in bone calcium content. The decreases in bone calcium content induced by bone-resorbing factors were completely inhibited by the coexistence of AHZ (10(-6) to 10(-4) mol/l). Also, AHZ (10(-5) mol/l) completely inhibited the PTH (10(-7) mol/l) or IL1 alpha (50 U/ml)-induced increase in medium glucose consumption and lactic acid production by bone tissue. Furthermore, AHZ (10(-5) mol/l) fairly blocked both PTH (10(-7) mol/l)-increased acid phosphatase and decreased alkaline phosphatase activities of bone tissue. The inhibitory effect of AHZ (10(-5) mol/l) on PTH (10(-7) mol/l)-stimulated bone resorption was clearly prevented by the presence of 10(-4) mol/l dipicolinate, a chelator of zinc. However, zinc sulfate (10(-7) to 10(-4) mol/l) did not inhibit the PTH (10(-7) mol/l)-stimulated bone resorption in tissue culture. These findings indicate that AHZ had a direct inhibitory effect on bone resorption in vitro, and the AHZ effect was found in the chemical form of zinc-chelated dipeptide.

MeSH terms

  • Acid Phosphatase / metabolism
  • Alkaline Phosphatase / metabolism
  • Animals
  • Anti-Ulcer Agents / pharmacology*
  • Bone Resorption*
  • Bone and Bones / drug effects*
  • Bone and Bones / enzymology
  • Bone and Bones / metabolism
  • Calcium / metabolism
  • Carnosine* / analogs & derivatives*
  • Culture Techniques
  • Dipeptides / pharmacology*
  • Glucose / metabolism
  • Lactates / metabolism
  • Lactic Acid
  • Male
  • Organometallic Compounds / pharmacology*
  • Rats
  • Rats, Wistar
  • Zinc Compounds


  • Anti-Ulcer Agents
  • Dipeptides
  • Lactates
  • Organometallic Compounds
  • Zinc Compounds
  • polaprezinc
  • Lactic Acid
  • Carnosine
  • Alkaline Phosphatase
  • Acid Phosphatase
  • Glucose
  • Calcium