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Background: Certain drugs such as glucocorticoids may interfere with the modulation of periodontal disease. In contrast, corticosteroid treatment has been associated with a protective effect with regard to periodontal breakdown, depending on the dose, pathway, and exposure time. Considering the potential relevance of nucleotidases in coordinating the cardiovascular system and inflammation processes, the aim of this study was to investigate the nucleotidase activities in the blood serum of rats with periodontal disease exposed chronically to inhaled corticosteroids., Methods: Adult male Wistar rats (n=26) were randomly assigned to one of the following four study groups: a control group that received no intervention; a periodontal disease group that received saline solution; a 'low dose' group that received 30 μg of budesonide daily; and a corresponding 'high dose' group that received 100 μg daily over a 15-day time course. The hydrolysis of ATP, ADP, and AMP were analysed in blood serum., Results: Periodontal disease diminished the hydrolysis of ATP and enhanced the hydrolysis of ADP. Repeated administration of either a low or high dose in the periodontal disease model of inhaled corticosteroids reversed the observed increase in ADP hydrolysis, and only the repeated administration of low doses of inhaled corticosteroids was able to reverse the decrease in the hydrolysis of ATP induced by periodontal disease., Conclusion: The variables investigated in this study may be involved in the pathophysiology of periodontal disease and may participate in the mechanisms that mediate the development of some of the side effects of inhaled corticosteroids., (Copyright © 2014 Elsevier Ltd. All rights reserved.)