ABSTRACT
BACKGROUND: Matrix metalloproteinases (MMPs) are proteolytic enzymes capable of degrading most macromolecules of the extracellular matrix. It has been assumed that an association exists between MMP activity and periodontal disease progression, but the precise role of MMPs in disease progression is still not fully clarified. Batimastat, or BB-94, is a synthetic broad-spectrum MMP inhibitor not previously examined in periodontal research. If there is an association between MMP activity and periodontal disease progression, then batimastat might be expected to reduce the progression of experimental periodontal disease in rats. OBJECTIVES: The objective of the present study was to determine the effects of batimastat on periodontal status in healthy Sprague-Dawley (SPRD) rats as well as in rats with ligature-induced experimental periodontal disease. METHODS AND RESULTS: Periodontal bone destruction was used as a means of evaluating periodontal destruction by measuring periodontal bone loss on defleshed rat jaws and periodontal bone support on radiographs of the jaws. There was significantly more periodontal bone destruction in the groups treated with batimastat than in the placebo and control groups. This accounted for both ligated and non-ligated groups, irrespective of whether periodontal bone loss (p < 0.05) or periodontal bone support (p < 0.05) were measured. CONCLUSION: In conclusion, the results of this study did not support the hypothesis that the MMP inhibitor batimastat could reduce the progression of experimental periodontal disease in rats. Instead, significantly increased bone destruction was found in rats treated with batimastat.
Subject(s)
Alveolar Bone Loss/prevention & control , Matrix Metalloproteinase Inhibitors , Phenylalanine/analogs & derivatives , Phenylalanine/therapeutic use , Protease Inhibitors/therapeutic use , Thiophenes/therapeutic use , Alveolar Bone Loss/diagnostic imaging , Alveolar Bone Loss/pathology , Alveolar Process/diagnostic imaging , Alveolar Process/drug effects , Alveolar Process/pathology , Analysis of Variance , Animals , Disease Progression , Injections, Intraperitoneal , Male , Placebos , Radiography, Dental, Digital , Random Allocation , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Although rats have been extensively used in periodontal research, pre-experimental periodontal inspection has not been given high priority in previous studies of experimental periodontal disease in rats. An inspection of 50 Sprague-Dawley rats, which were to be used in a model of experimental periodontal disease, revealed signs of periodontal disease in a considerable proportion of the animals. OBJECTIVES: The objectives of the present study were to describe disease progression, identify factors responsible for induction of periodontal disease and test a method for breeding of healthy rats. METHODS AND RESULTS: A longitudinal study revealed that 33% of rats, bred under the same conditions, showed signs of periodontal disease during, or shortly after, eruption of the molars. Regular diet caused significantly more horizontal bone loss (P = 0.0001) and significantly less periodontal bone support (P < 0.0001) than the same kind of diet with a smaller grain size. Wood chip bedding in the rats' cages significantly reduced periodontal bone support (P < 0.0001) compared to a wire mesh floor and a simultaneous use of regular diet and bedding decreased it even further (P = 0.0023). Finally, by using finely milled diet, a wire mesh floor and tap water, instead of conventional breeding methods of regular diet, bedding and acidic water, it was possible to breed rats with minimal signs of periodontal disease. CONCLUSIONS: The results of the present study emphasize the need for pre- experimental examination of rats. They also show that diet and bedding conditions have the potential of seriously influencing outcomes of studies of periodontal disease in rats.
