Smokeless tobacco contains a nonnicotine inhibitor of bone metabolism.
The effects of smokeless tobacco on bone were investigated using tibiae from chick embryos. The bones were cultured in nicotine (15-1500 micrograms/ml) or in smokeless tobacco extract (STE, 15 mg tobacco/ml culture medium) and the effects on bone glucose metabolism (oxygen consumption and lactate production) and collagen synthesis ([3H]proline hydroxylation) were tested in vitro. Only the highest concentration of nicotine tested produced substantial effects as demonstrated by decreased oxygen consumption and [3H]hydroxyproline content (82 and 90%, respectively) and by a 15% increase in lactate production. Results with STE, which contained nicotine concentrations ranging from 104 to 125 micrograms/ml, showed similarly reduced [3H]hydroxyproline content (90%), but oxygen consumption was only reduced 36%, while lactate production was elevated 60%. The ability of the bones to recover from treatment with STE was demonstrated by increased oxygen consumption and [3H]hydroxyproline content (18 and 78%, respectively) and decreased lactate production (47%) compared to the STE-treated bones. These findings suggest the following conclusions: (1) both nicotine and STE at concentrations found in the saliva of smokeless tobacco users stimulate glycolysis and markedly inhibit bone collagen synthesis and mitochondrial activity; (2) effects of STE on bone are not due to nicotine; and (3) under the conditions studied, bone partially recovers from the effects of STE.
Department of Pharmacology, University of Louisville, Kentucky 40292.
R J
RJ
Galvin
W K
WK
Ramp
L G
LG
Lenz
D000328:Adult; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000032:analysis; D002642:Chick Embryo; D003094:Collagen / Q000096:biosynthesis; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D009538:Nicotine / Q000494:pharmacology; D010101:Oxygen Consumption; D010947:Plants, Toxic; D011392:Proline / Q000378:metabolism; D014026:Nicotiana / Q000032:analysis; D014030:Tobacco, Smokeless / Q000032:analysis
D007773:Lactates; D019344:Lactic Acid; D009538:Nicotine; D003094:Collagen; D011392:Proline; D005947:Glucose; D006909:Hydroxyproline; D002118:Calcium