Inhibitory effect of beta-alanyl-L-histidinato zinc on bone resorption in tissue culture.
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.
Yamaguchi
M
M
Laboratory of Metabolism and Endocrinology, Graduate School of Nutritional Sciences, University of Shizuoka, Japan.
Segawa
Y
Y
Shimokawa
N
N
Tsuzuike
N
N
Tagashira
E
E
D000135:Acid Phosphatase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002336:Carnosine / Q000031:analogs & derivatives*; D046508:Culture Techniques; D004151:Dipeptides / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017967:Zinc Compounds
D000897:Anti-Ulcer Agents; D004151:Dipeptides; D007773:Lactates; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D019344:Lactic Acid; D002336:Carnosine; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D005947:Glucose; D002118:Calcium