Effects of low dose doxycycline and bisphosphonate clodronate on gingival levels of matrix metalloproteinases -2, -9, interleukin-1b and alveolar bone loss in diabetic rats. a histological and immunohistichemical study

Previous researhes indicated that diabetes increases the risk of periodontal diseases. Doxycycline has been widely used in periodontal treatment for its antimicrobial and anti-enzymatic effects. Bisphosphonates have been shown to inhibit alveoler bone resorption. The aim of this research is to evaluate the reduction capacity of low dose doxycycline combined using with a bisphosphonate clodronate on gingival levels of MMP-2, -9, interleukin-1 ? and alveolar bone loss and compare this treatment model with mono therapies in diabetic rats50 adult Wistar rats were divided into five study groups: Group 1 (diabetes control), group 2 (diabetes + periodontitis), group 3 (diabetes + periodontitis + doxycycline), group 4 (diabet + periodontitis + clodronate), group 5 (diabetes + periodontitis + doxycycline + clodronate). Doxycycline and clodronate were given as a single agent or as combination therapy during the 7 days of the post -experimental periodontitis period. On day 7, the rats were sacrificed and the mobility of the tooth were recorded and block biopsies were removed. The gingival tissues were analyzed histologically and immunohistochemically for expression of MMP-2, MMP-9 and IL-1ß. Alveoler bone loss was evaluated morphometrically under a light microscope. Data analysis was performed statistically by Kruskal Wallis and post hoc Tukey tests and Spearman correlation testAlveoler bone loss and inflammation scores were significantly higher in the group 2, 3, 4 and 5 than group 1 (p<0,05). Inflammation scores were significantly lower in the group 4 than group 3 (p<0,05). Tooth mobility was significantly increased in the groups 2, 3, 4, 5 compared to group 1(p<0,05). In addition, mobility score was statistically lower in the group 4 compared to group 2 and 5 (p<0,05). MMP-9 expressions were significantly higher in the group 2 than in the group 1 (p<0,05) and significantly lower in group 3 than 1. At the same time, MMP-9 expressions were higher in group 2 than group 3, 4 and 5 (p<0,01) and significantly higher in group 5 than 3 (p<0,05). No significant differences were found in MMP-2 expressions among the study groups. IL-1ß expressions were significantly lower in the group 1, 3, 4, 5 than 2 (p<0,01Our findings suggest that combined clodronate and doxycycline and monotherapies may significantly inhibit MMP-9 and IL-1ß expressions. However, to better understanding the effects of these drugs on the gingival tissues and alveolar bone, new studies with large amount of groups and test subjects are necessary.