Comparison of etoricoxib and indomethacin for the treatment of experimental periodontitis in rats

We investigated the effect of etoricoxib, a selective cyclooxygenase-2 inhibitor, and indomethacin, a non-selective cyclooxygenase inhibitor, on experimental periodontitis, and compared their gastrointestinal side effects. A ligature was placed around the second upper left molars of female Wistar rats (160 to 200 g). Animals (6 per group) were treated daily with oral doses of 3 or 9 mg/kg etoricoxib, 5 mg/kg indomethacin, or 0.2 mL saline, starting 5 days after the induction of periodontitis, when bone resorption was detected, until the sacrifice on the 11th day. The weight and survival rate were monitored. Alveolar bone loss (ABL) was measured as the sum of distances between the cusp tips and the alveolar bone. The gastric mucosa was examined macroscopically and the periodontium and gastric and intestinal mucosa were examined by histopathology. The ongoing ABL was significantly inhibited (P < 0.05) by 3 and 9 mg/kg etoricoxib and by indomethacin: control = 4.08 ± 0.47 mm; etoricoxib (3 mg/kg) = 1.89 ± 0.26 mm; etoricoxib (9 mg/kg) = 1.02 ± 0.14 mm; indomethacin = 0.64 ± 0.15 mm. Histopathology of periodontium showed that etoricoxib and indomethacin reduced inflammatory cell infiltration, ABL, and cementum and collagen fiber destruction. Macroscopic and histopathological analysis of gastric and intestinal mucosa demonstrated that etoricoxib induces less damage than indomethacin. Animals that received indomethacin presented weight loss starting on the 7th day, and higher mortality rate (58.3%) compared to etoricoxib (0%). Treatment with etoricoxib, even starting when ABL is detected, reduces inflammation and cementum and bone resorption, with fewer gastrointestinal side effects

Apoptosis in human liver carcinoma caused by gold nanoparticles in combination with carvedilol is mediated via modulation of MAPK/Akt/mTOR pathway and EGFR/FAAD proteins

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

The receptor AT1 appears to be important for the maintenance of bone mass and AT2 receptor function in periodontal bone loss appears to be regulated by AT1 receptor

A large number of experimental studies has demonstrated that angiotensin II (Ang II) is involved in key events of the inflammatory process. This study aimed to evaluate the role of Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors on periodontitis. Methods: Experimental periodontitis was induced by placing a 5.0 nylon thread ligature around the second upper left molar of AT1 mice, no-ligature or ligature (AT1-NL and AT1-L), AT2 (AT2-NL or AT2-L) and wild type (WT-NL or L). Alveolar bone loss was scanned using Micro-CT. Cytokines, peptides and enzymes were analyzed from gingival tissues by Elisa and RT-PCR. Results: The blockade of AT1 receptor resulted in bone loss, even in healthy animals. Ang II receptor blockades did not prevent linear bone loss. Ang II and Ang 1-7 levels were significantly increased in the AT2-L (p < 0.01) group compared to AT2-NL and AT1-L. The genic expression of the Mas receptor was significantly increased in WT-L and AT2-L compared to (WT-NL and AT2-NL, respectively) and in AT1-L. Conclusions: Our data suggest that the receptor AT1 appears to be important for the maintenance of bone mass. AT2 receptor molecular function in periodontitis appears to be regulated by AT1

AT1 and AT2 receptor knockout changed osteonectin and bone density in mice in periodontal inflammation experimental model

BACKGROUND: The aim of this study was to evaluate the role of AT1 and AT2 receptors in a periodontal inflammation experimental model. METHODS: Periodontal inflammation was induced by LPS/Porphyromonas gingivalis. Maxillae, femur, and vertebra were scanned using Micro-CT. Maxillae were analyzed histopathologically, immunohistochemically, and by RT-PCR. RESULTS: The vertebra showed decreased BMD in AT1 H compared with WT H (p < 0.05). The femur showed increased Tb.Sp for AT1 H and AT2 H, p < 0.01 and p < 0.05, respectively. The Tb.N was decreased in the vertebra (WT H-AT1 H: p < 0.05; WT H-AT2 H: p < 0.05) and in the femur (WT H-AT1 H: p < 0.01; WT H-AT2 H: p < 0.05). AT1 PD increased linear bone loss (p < 0.05) and decreased osteoblast cells (p < 0.05). RANKL immunostaining was intense for AT1 PD and WT PD (p < 0.001). OPG was intense in the WT H, WT PD, and AT2 PD when compared to AT1 PD (p < 0.001). AT1 PD showed weak immunostaining for osteocalcin compared with WT H, WT PD, and AT2 PD (p < 0.001). AT1 H showed significantly stronger immunostaining for osteonectin in fibroblasts compared to AT2 H (p < 0.01). CONCLUSION: AT1 receptor knockout changed bone density, the quality and number of bone trabeculae, decreased the number of osteoblast cells, and increased osteonectin in fibroblasts

Low-dose doxycycline prevents inflammatory bone resorption in rats

Matrix metalloproteinases (MMP) are considered to be key initiators of collagen degradation, thus contributing to bone resorption in inflammatory diseases. We determined whether subantimicrobial doses of doxycycline (DX) (<=10 mg kg-1 day-1), a known MMP inhibitor, could inhibit bone resorption in an experimental periodontitis model. Thirty male Wistar rats (180-200 g) were subjected to placement of a nylon thread ligature around the maxillary molars and sacrificed after 7 days. Alveolar bone loss (ABL) was measured macroscopically in one hemiarcade and the contralateral hemiarcade was processed for histopathologic analysis. Groups of six animals each were treated with DX (2.5, 5 or 10 mg kg-1 day-1, sc, 7 days) and compared to nontreated (NT) rats. NT rats displayed significant ABL, severe mononuclear cell influx and increase in osteoclast numbers, which were significantly reduced by 5 or 10 mg kg-1 day-1 DX. These data show that DX inhibits inflammatory bone resorption in a manner that is independent of its antimicrobial properties

Pharmacological and histopathological study of cyclophosphamide-induced hemorrhagic cystitis - comparison of the effects of dexamethasone and Mesna

Chemotherapy with oxazaphosphorines, such as cyclophosphamide (CYP), is often limited by unacceptable urotoxicity. Without uroprotection, hemorrhagic cystitis (HC) becomes dose-limiting. To compare the uroprotective efficacy of classical 2-mercaptoethanesulfonic acid (Mesna) treatment with dexamethasone in CYP-induced HC, male Wistar rats (150-200 g; N = 6 in each group) were treated with saline or Mesna (40 mg/kg, ip) immediately and 4 and 8 h after ip administration of CYP (200 mg/kg). One, 2 or 3 doses of Mesna were replaced with dexamethasone (1 mg/kg, ip). The animals were sacrificed 24 h later. Cystitis was evaluated by determining the changes in bladder wet weight (BWW) and by macroscopic and microscopic analysis. CYP treatment induced a marked increased in BWW (162%, P&lt;0.05), which was significantly inhibited by treatment with 3 doses of Mesna (P&lt;0.05; 80%). The replacement of 1 or 2 doses of Mesna with dexamethasone reduced the increase in BWW by 83.3 and 95%, respectively. Macroscopic analysis of the bladder of rats with CYP-induced HC showed severe edema and hemorrhage, confirmed by microscopic analysis, that also showed mucosal erosion, inflammatory cell infiltration and ulcerations. The replacement of 1 or 2 doses of Mesna with dexamethasone inhibited the CYP-induced increase in BWW and almost abolished the macroscopic and microscopic alterations, with no significant difference between the effects of Mesna and dexamethasone, indicating that both drugs were efficient in blocking HC. However, although the replacement of all Mesna doses with dexamethasone reduced the edema, it did not prevent HC, suggesting that Mesna is necessary for the initial uroprotection

Long-term ethanol intoxication reduces inflammatory responses in rats

The anti-inflammatory effects of long-term ethanol intoxication were determined during ethanol treatment and withdrawal on the basis of neutrophil and eosinophil migration, hind paw edema and mast cell degranulation. Male Wistar rats (180-200 g, around 2 months of age) were exposed to increasing concentrations of ethanol vapor over a 10-day period. One group was evaluated immediately after exposure (treated group - intoxicated), and another was studied 7 h later (withdrawal group). Ethanol inhalation treatment significantly inhibited carrageenan- (62% for the intoxicated group, N = 5, and 35% for the withdrawal group, N = 6) and dextran-induced paw edema (32% for intoxicated rats and 26% for withdrawal rats, N = 5 per group). Ethanol inhalation significantly reduced carrageenan-induced neutrophil migration (95% for intoxicated rats and 41% for withdrawn rats, N = 6 per group) into a subcutaneous 6-day-old air pouch, and Sephadex-induced eosinophil migration to the rat peritoneal cavity (100% for intoxicated rats and 64% for withdrawn rats, N = 6 per group). A significant decrease of mast cell degranulation was also demonstrated (control, 82%; intoxicated, 49%; withdrawn, 51%, N = 6, 6 and 8, respectively). Total leukocyte and neutrophil counts in venous blood increased significantly during the 10 days of ethanol inhalation (leukocytes, 13, 27 and 40%; neutrophils, 42, 238 and 252%, respectively, on days 5, 9 and 10, N = 7, 6 and 6). The cell counts decreased during withdrawal, but were still significantly elevated (leukocytes, 10%; neutrophils, 246%, N = 6). These findings indicate that both the cellular and vascular components of the inflammatory response are compromised by long-term ethanol intoxication and remain reduced during the withdrawal period