Long-term testosterone depletion attenuates inflammatory bone resorption in the ligature-induced periodontal disease model.

BACKGROUND: Testosterone is known to affect bone in physiological and pathological conditions. The purpose of this study is to evaluate the role of testosterone in experimental periodontal disease in rats. METHODS: In this study we used a ligature model of periodontal disease in rats submitted to orchiectomy (OCX, testosterone depletion) with and without testosterone replacement therapy (TR). Control animals were sham-operated and retained physiological testosterone levels. Sixty-two days after orchiectomy and sham operations, ligatures were placed around the lower first molars for 2 weeks to induce experimental periodontal disease. Negative control animals received no ligatures. The outcomes assessed in the periodontal tissues were: inflammatory cytokine expression by enzyme-linked immunosorbent assay (ELISA), stereometric analysis of the inflammatory process and quantitation of inflammatory bone resorption by microcomputed tomography (µ-CT). RESULTS: The OCX+TR group showed the greatest increase in fibroblastic cells and blood vessels with reduced inflammatory cell numbers in the gingival tissue with induction of periodontal disease. There were no significant differences between OCX and Sham-operated groups in all the stereometric parameters assessed. Ligature placement induced inflammatory bone resorption, which was significantly attenuated in OCX animals. Experimental periodontitis induced a significant increase in interleukin (IL)-1ß, but the lowest levels were observed in the periodontitis/OCX group. IL-6 levels were not affected by OCX, but were significantly reduced in OCX+TR animals. CONCLUSION: The findings of the present study suggest that testosterone depletion attenuates inflammatory bone resorption in ligature-induced periodontitis, which may be partly mediated via decreased production of IL-1ß.

Chemopreventive activity of systemically administered curcumin on oral cancer in the 4-nitroquinoline 1-oxide model.

Curcumin has therapeutic potential in preventing several types of cancer, including colon, liver, prostate, and breast. The goal of this study was to evaluate the chemopreventive activity of systemically administered curcumin on oral carcinogenesis induced by 4-nitroquinolone-1-oxide (4-NQO). A total of 50 male albino rats, Rattus norvegicus, (Holtzman), were divided into five groups (n = 10 per group). Four of these groups were exposed to 50 ppm 4-NQO in their drinking water ad libitum for 8 or 12 weeks, two groups were treated with curcumin by oral gavage at 30 or 100 mg/kg per day, and one group was treated with corn oil (vehicle) only. The negative control group was euthanized at baseline. Tongues of all animals were removed after euthanasia and used in the subsequent analysis because the tongue is the primary site of carcinogenesis in this model. Descriptive histological analysis and immunohistochemistry for PCNA, Bcl-2, SOCS1 e-3, and STAT3 were performed to assess the oncogenic process. The gene expression of Vimentin, E-cadherin, N-cadherin, or TWIST1 was assessed using RT-qPCR as a representative of epithelial-mesenchymal transition (EMT) events. The administration of curcumin at 100 mg/kg during the 12 weeks markedly decreased the expression of PCNA, Bcl-2, SOCS1 e -3, and STAT3. Curcumin also minimized the cellular atypia under microscopic analysis and diminished the expression of the genes associated with EMT. These findings demonstrate that the systemic administration of curcumin has chemopreventive activity during oral carcinogenesis induced by 4-NQO.