الفهرس 
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Abstract
The aim of this study is to evaluate the effect of different disinfecting antibiotic combinations regimens on certain inflammatory biomarkers in mature teeth with chronic apical periodontitis in dogs. The targeted biomarkers were IL-17 which is a pro-inflammatory cytokine, TGF- β which is a pleiotropic cytokine with dual pro or anti-inflammatory effects, and MMP-13 which is a collagenase of the metalloproteinase family. Three different antibiotics disinfectants were used to assess their effect: Ciprofloxacin, DAP (equal volumes of metronidazole and Doxycycline) and TAP (similar to DAP with an added similar volume of Doxycycline). Eight mature dogs were selected for this study. from each dog, three two-rooted premolars from the lower jaw unilaterally were used; with a total 6 root apices/dog. Access cavities were made, periapical pathosis initiation was provoked and the teeth were left exposed to the oral environment for 4 weeks. The dogs were then randomly allocated to four groups: two dogs per group:
group I: which represent the control group where only apicectomy was done after 4 weeks from lesion induction to collect the formed periapical lesions and assess the “reference levels” of the biological markers of interest.
Remaining groups received a disinfection step as follows:
group II: disinfection using CP.
group III: disinfection using DAP
group IV: disinfection using TAP
After 4 weeks, teeth of groups II, III and IV were cleaned and shaped under aseptic conditions and the use of NaOCl and EDTA before the placement of CP, DAP or TAP respectively as intracanal medications and providing coronal seal. 4 weeks after apicectomy procedures were performed as in group I to collect the sample tissues. All obtained 48 samples collected from the 4 groups (12 roots/group) were processed for the immunofluorescent examination of the biomarkers’ level change from reference level in correlation to the disinfecting antibiotic used. from each sample a series of sequential calibrated photomicrographs were taken with the designated light filter suitable for the used fluorochrome. Using ZEN 2 blue edition image analysis software obtained images were quantified for average intensity (intensity per image area) of the fluorochrome specific for the cytokine assessed, and thus its expression; the greater the intensity, the greater the level
Statistical analyses of the results showed that:
For IL-17: CP, DAP and TAP caused decreased levels of IL-17 compared to control suggesting decreased inflammation. Although the level decrease was not statistically significant from one disinfectant to another nor from the control group, DAP showed least reduction in IL-17 level and hence was the most to reduce inflammation.
For TGF- β: CP caused a statistically significant increase in TGF- β level compared to control. In the presence of suitable biomarkers in the environment, this level increase is indicative of reduced inflammation. DAP and TAP groups showed decreased TGF- β level than control thus suggesting inflammation. This decrease was not statistically significant though.
For MMP-13: CP, DAP and TAP caused statistically significant increase in the MMP-13 level, thus suggestive of increased inflammation. CP showed the highest value for MMP-13 levels followed by DAP and TAP that although not significant from one were significantly lower than CP but significantly higher than control group.
Upon correlating all three biomarkers, only TGF- β and MMP-13 showed a statistically significant positive correlation.
Conclusions:
Under the limitations of the present study, and owing to the complexity of inflammatory dynamics, it can be concluded that:
1-Used antibiotic/antibiotic combinations can not be deemed purely pro or anti-inflammatory as a single disinfecting agent can lower the level of a traditionally considered inflammatory biomarker but increases the level of another.
2- The resulting positive correlation between TGF- β and MMP-13 might be indicative of a potential anti-inflammatory role of the latter. Thus, an increase in expression level might not necessarily mean inflammation.
3- Considering the previous point, Ciprofloxacin would have had most favorable results on the studied biomarkers’ levels.
Recommendations:
1-Further studies with multiple sample collection intervals may shed more light on the dynamics of the inflammatory process; where the detected biomarkers’ levels might be only initial or a function of the timing in which the samples were collected.
2- Future studies are needed to furtherly investigate a potential and non-traditional role of MMPs