Avaliação de efeitos biológicos de antiinflamatórios derivados do ácido propiônico através de modelos experimentais em nível molecular e celular

Derivatives of propionic acid NSAIDs are irreversible inhibitors of cyclooxygenase enzyme widely used. The aim of this study was to evaluate, through different experimental models, biological effects of derivatives of propionic acid (fenoprofen, naproxen, ibuprofen and ketoprofen) in cellular and molecular level. The labeling of blood constituents with technetium-99m (99mTc) and morphological analysis of erythrocytes of blood of rats, as well as growth, survival of cultures of Escherichia coli (E. coli) and the assessment of bacterial plasmid electrophoretic profiles were models used for experimental evaluation of possible biological effects of antiinflammatory drugs. The results show that, in general, anti-inflammatory drugs evaluated were not able to alter the labeling of blood constituents with 99mTc, the morphology of red blood cells from blood of rats, as well as the growth of cultures of E. coli and the electrophoretic profile of plasmid DNA. However, naproxen appears to cytotoxic effect on bacterial cultures, plasmids and genotoxic effects in reducing the action of stannous chloride in cultures of E. coli. The use of experimental fast performance and low cost was important for assessment of biological effects, contributing to a better understanding of the properties of propionic acid derivatives studied. anti-inflammatory, blood constituents, technetium-99m, stannous chloride, Escherichia coli; DNA

Efeitos da azilsartana sobre a doença periodontal em um modelo experimental com ratos wistar

Periodontal diseases, highly prevalent disease in worldwide population, manifest primarily in two distinct entities: plaque-induced gingivitis and periodontitis. Periodontitis is a chronic inflammatory disease characterized of different levels of collagen, cementum, and alveolar bone destruction. Recent experimental studies demonstrated anti-inflammatory and antirreabsortive effect of antihypertensive agents of the angiotensin II receptor blockers class on periodontal disease. The aim of this study was to evaluate the effects of azilsartan (AZT), a potent inhibitor of the angiotensin II receptor which has minimal adverse effects on bone loss, inflammation, and the expression of matrix metallo proteinases (MMPs), receptor activator of nuclear factor kB ligand (RANKL), receptor activator of nuclear factor kB (RANK), osteoprotegerin (OPG), cyclooxygenase-2 (COX-2), and cathepsin K in periodontal tissue in a rat model of ligature-induced periodontitis. Male Wistar albino rats were randomly divided into 5 groups of 20 rats each: (1) nonligated, water; (2) ligated, water; (3) ligated, 1 mg/kg AZT; (4) ligated, 5 mg/kg AZT; and (5) ligated, 10 mg/kg AZT. All groups were treated with water or AZT for 10 days. Periodontal tissues were analyzed by morphometric exam, histopathology and immunohistochemical detection of MMP-2, MMP-9, COX-2, RANKL, RANK, OPG, and cathepsin K. Levels of IL-1b, IL-10, TNF-a, myeloperoxidase (MPO), and glutathione (GSH) were determined by ELISA. Treatment with 5 mg/kg AZT resulted in reduced MPO (p˂0.05) and IL-1b (p˂0.05) levels and increased in Il-10 levels (p˂0.05). It was observed a reduced expression of MMP-2, MMP-9, COX-2, RANK, RANKL, cathepsin K, and a increased expression of OPG in the animals subjected to experimental periodontitis and threated with AZT (5 mg/kg). Conclusions: These findings suggest an anti-inflammatory and anti-reabsortive effects of AZT on ligature-induced periodontitis in rats.

Queilite actínica: expressão imuno-histoquímica da cox-2 e avaliação do diclofenaco sódico gel como uma terapia alternativa

Actinic cheilitis (AC) is a potentially malignant disorder which affects the lip vermilion and results from chronic exposure to sunlight. Currently, it is not possible to predict which cases of AC may progress to squamous cell carcinoma, and therefore, some biomolecular markers have been researched. Cyclooxygenase 2 (COX-2) is an enzyme associated with inflammatory response which is overexpressed in oral cancer; however, little is known about the role of this protein in actinic cheilitis. About the treatment of this lesion, currently available therapeutic modalities to AC may cause cytotoxic effects and deleterious results to patients. Therefore, the aim of this study was to evaluate the immunoexpression of COX-2 in AC of different risks of malignant transformation and analyse, through clinical follow-up, the efficacy of diclofenac sodium 3% gel in the treatment of this condition. Epithelial immunoexpression of COX-2 was analysed semi-quantitatively in 90 cases of AC classified as low risk (n = 55) and high risk (n = 35) of malignant transformation, in which the scores were assigned: (0) 0 to 5% of positive cells - Negative; (1) 6 to 30% of positive cells - Low expression; (2) 31 to 100% of positive cells - High expression. The chi-square test of Pearson was conducted to verify possible associations between immunoexpression of COX-2 and histologic grade of actinic cheilitis. The weighted kappa coefficient denoted a good interobserver agreement (0.677). Nineteen patients diagnosed with AC were instructed to perform topical application of the gel three times a day for a period of 90 days. In each biweekly visit, a follow-up record was accomplished through digital photographs and after treatment was completed, two researchers analysed all the images to assess clinical aspects of the lip. Furthermore, tolerability to the drug and patient satisfaction after treatment were evaluated. COX-2 was overexpressed in 74.4% of AC cases. Both low and high-risk groups revealed predominance of score 3, followed by scores 2 and 1. There was no significant association (p = 0.315) between COX-2 expression and histological grading. Among the total number of participants of this clinical study, ten showed total remission of all clinical features of the lesion and three had partial improvement of these characteristics. One participant presented worsening of the clinical condition. In five cases, the treatment was discontinued due to development of mild adverse effects at the site of gel application. Regarding analysis of satisfaction and tolerability to the drug, most patients were fully satisfied with the therapy (n = 11) and reported that the drug was not irritating to the lips (n = 9). Our study demonstrates that high expression of COX-2 is common in AC; however, this protein was not associated with malignant transformation risk of the analysed cases. Topical application of diclofenac sodium 3% gel provided a convenient and well tolerated approach in most cases, and may be a promising alternative for the treatment of actinic cheilitis.