Aliskiren Attenuates the Inflammatory Response and Wound Healing Process in Diabetic Mice With Periodontal Disease.

The aim of this study was to characterize the role of local RAS (renin-angiotensin system) in the inflammatory response of normal (N) and diabetic (D) mice with periodontal disease (PD). Diabetes Mellitus (DM) was induced by peritoneal injection of streptozotocin in Balb/c mice. PD was induced by ligature around the first molar in both N and D, irrespective of whether they were treated with aliskiren (50 mg/kg, Alisk). Mandibles were harvested for histomorphometric analyses, and gingival tissue (GT) was collected to evaluate gene expression and extracellular matrix components (ECM). Immunohistochemical (IHC) analyses were used to localize RAS in GT. The production of C-reactive protein (CRP), IL-1ß, CXCL2, and CCL8 was evaluated by enzyme-linked immunosorbent assay (ELISA). Renin was found to exacerbate the inflammation and periodontal bone loss at 14 days after PD, and Alisk inhibited this process in GT of N and D. PD increased CRP, CXCL2, CCL8, and IL-1ß production in both animals. Alisk could inhibit CRP, CXCL2, and CCL8 primarily in D animals. However, only CCL8 was decreased in N animals after Alisk pretreatment. PD enhanced expression and production of AGT, ACE, AT1R, and AT2R in both N and D. AT1R expression was higher in D with PD, and AT2R expression was higher in N with PD. ACE2 and receptor Mas (MasR) expression and production was elevated in the control group of both animals. PD inhibited ACE2 in N but not in D. MasR expression was unaffected in both N and D with PD. Alisk reduced expression and production of all RAS components in GT of both animals, except for ACE2 in N. RAS staining was observed in all layers of epithelium, basal cell layer, and lamina propria and was higher in N with PD. Col1a1, Col1a2, Col3a1, and fibronectin (Fn1) were increased in both animals with PD. Alisk inhibited Col1a1 and Fn in both animals, Col1a2 was decreased only in D, while levels of Col3a1 remained unchanged in all animal groups. In conclusion, these data demonstrated the presence and functional role of local RAS in GT, exacerbating the inflammatory response, periodontal bone loss, and wound healing processes in both N and D animal groups. In addition, Alisk was able to significantly reduce gingival inflammation, excessive wound healing processes, and periodontal bone loss.

Biodistribution of 99Mo in rats

The modification of 99Mo standard metabolism in the presence of MDP would alter the dosimetry of this radionuclide in nuclear medicine patients. Therefore, the objective of this work is to evaluate the influence of MDP in the biodistribution of 99Mo. Wistar rats were divided in two groups of six animals, being inoculated respectively 99Molibdate and 99Mo+MDP via plex ocular. The biodistribution study was carried out after 10 and 120 minutes respectively. The organs were counted with a NaI(Tl) detector. The uptake values did not present significant differences among the groups. An in vitro study through planar chromatography was carried out to determine the affinity between molybdenum and MDP. The results show that 99Mo has low affinity both to propanone and NaCl-0.9 percent solution. However, 99Mo in the presence of MDP presented affinity to NaCl-0.9% solution and low affinity to propanone suggesting that 99Mo was bound to MDP under the conditions of the experiment.

A modificação do metabolismo padrão do 99Mo em presença de MDP levaria a alterações na dosimetria deste radionuclídeo em pacientes de medicina nuclear. Assim, o objetivo deste trabalho é avaliar a influência do MDP na biodistribuição de 99Mo. Ratos Wistar foram divididos em dois grupos de seis animais, sendo inoculados respectivamente com 99Molibdato e 99Molibdato+MDP via plexo ocular. O estudo de biodistribuição foi realizado após 10 e 120 minutos respectivamente. Os órgãos foram contados com detector NaI(Tl). Os valores de uptake não apresentaram diferenças significativas entre os grupos. Foi realizado um estudo in vitro através de cromatografia planar para determinar a afinidade entre o molibdênio e o MDP. Os resultados mostraram que o molibdênio tem baixa afinidade tanto pela propanona quanto pela solução 0.9 por cento de NaCl. Entretanto, o molibdênio em presença de MDP apresentou afinidade pela solução 0.9% de NaCl e baixa afinidade pela propanona, sugering ter ocorrido ligação entre o 99Mo e o MDP nas condições do experimento.