Heteroleptic oxidovanadium(IV)-malate complex improves glucose uptake in HepG2 and enhances insulin action in streptozotocin-induced diabetic rats.

Diabetes mellitus, a complex and heterogeneous disease associated with hyperglycemia, is a leading cause of mortality and reduces life expectancy. Vanadium complexes have been studied for the treatment of diabetes. The effect of complex [VO(bpy)(mal)]·H2O (complex A) was evaluated in a human hepatocarcinoma (HepG2) cell line and in streptozotocin (STZ)-induced diabetic male Wistar rats conditioned in seven groups with different treatments (n = 10 animals per group). Electron paramagnetic resonance and 51V NMR analyses of complex A in high-glucose Dulbecco's Modified Eagle Medium (DMEM) revealed the oxidation and hydrolysis of the oxidovanadium(IV) complex over a period of 24 h at 37 °C to give low-nuclearity vanadates "V1" (H2VO4-), "V2" (H2V2O72-), and "V4" (V4O124-). In HepG2 cells, complex A exhibited low cytotoxic effects at concentrations 2.5 to 7.5 µmol L-1 (IC50 10.53 µmol L-1) and increased glucose uptake (2-NBDG) up to 93%, an effect similar to insulin. In STZ-induced diabetic rats, complex A at 10 and 30 mg kg-1 administered by oral gavage for 12 days did not affect the animals, suggesting low toxicity or metabolic impairment during the experimental period. Compared to insulin treatment alone, complex A (30 mg kg-1) in association with insulin was found to improve glycemia (30.6 ± 6.3 mmol L-1 vs. 21.1 ± 8.6 mmol L-1, respectively; p = 0.002), resulting in approximately 30% additional reduction in glycemia. The insulin-enhancing effect of complex A was associated with low toxicity and was achieved via oral administration, suggesting the potential of complex A as a promising candidate for the adjuvant treatment of diabetes.

Peanut skin polyphenols inhibit toxicity induced by advanced glycation end-products in RAW264.7 macrophages.

This is the first work to use a polyphenolic fraction derived from peanut skin to attenuate the toxicity induced by advanced glycation-end products (AGEs) in RAW264.7 macrophages. The RAW264.7 cells were stimulated by AGEs using the bovine serum albumin-fructose (BSA-FRU), bovine serum albumin-methylglyoxal (BSA-MGO) and arginine-methylglyoxal (ARG-MGO) models. The AGEs increased considerably the levels of reactive oxygen species and the gene expression of proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide. Twenty-eight polyphenols, including catechin, phenolic acids, and resveratrol were annotated in peanut skin extract (PSE) with the use of ultra-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UPLC-QTOF/MSE) and to the UNIFI Scientific Information System. The administration of PSE at 100 and 150 µg/mL significantly inhibited oxidative stress, by suppressing the production of reactive oxygen species up to 70% and reducing the production of nitric oxide, IL-6 and TNF-α up to 1.7-, 10- and 107-fold, respectively.

Inter-relação da doença periodontal e doença intestinal inflamatória / The relationship of periodontal disease and inflammatory intestinal disease ­ literature review

O presente trabalho busca, através da revisão de literatura, exemplificar um entendimento mais plausível entre a inter-relação da doença periodontal e a doença intestinal. Essa inter-relação pode ser exemplificada no estudo das citocinas, as quais influenciam a atividade, a diferenciação, a proliferação e a sobrevida da célula imunológica, assim como regulam a produção e a atividade de outras citocinas, que podem aumentar (pró-inflamatórias Th1) ou atenuar (anti-inflamatórias Th2) a resposta inflamatória nas doenças em questão. A doença periodontal é o processo inflamatório em resposta a antígenos bacterianos da placa dentária que se acumulam ao longo da margem gengival. Sua manifestação inicial é a gengivite, podendo evoluir para a periodontite, estágio no qual poderá ocorrer a destruição tecidual. Já a doença intestinal é uma denominação geral para um grupo de distúrbios inflamatórios crônicos que envolvem o trato gastrointestinal, de etiologia específica desconhecida. A resposta imunoinflamatória é o fator-chave tanto na periodontite quanto na doença intestinal. Estas são caracterizadas por uma expressiva produção local de mediadores inflamatórios. A existência de mecanismos inflamatórios e de destruição tecidual similares pode ser a provável causa da maior prevalência de periodontite moderada a severa encontrada em pacientes com doenças intestinais. Apesar de todos os estudos, é necessária a determinação de um perfil mais específico entre a suscetibilidade da doença periodontal em relação a pacientes com doenças intestinais, a fim de futuramente possuir o desenvolvimento de drogas eficazes capazes de restituir o equilíbrio imunológico fundamental para o paciente, que auxiliará tanto no controle das doenças periodontais quanto nas doenças inflamatórias.

The present work searches through the literature review to exemplify a more plausible understanding between the interrelationship of periodontal disease and intestinal disease. This interrelationship can be exemplified in the study of cytokines, which infl uence the activity, differentiation, proliferation and survival of the immune cell, as well as regulate the production and activity of other cytokines, which may increase (pro-inflammatory Th1 ) or attenuate (Th2 anti-inflammatory) inflammatory response in the diseases in question. Periodontal disease is the inflammatory process in response to bacterial plaque antigens that accumulate along the gingival margin. Its initial manifestation is gingivitis, which may progress to periodontitis where tissue destruction may occur. Intestinal disease is a general term for a group of chronic inflammatory disorders involving the gastrointestinal tract of unknown etiology. The immuno-inflammatory response is the key factor in both periodontitis and intestinal disease, being these characterized by a significant local production of inflammatory mediators. The existence of similar inflammatory mechanisms and tissue destruction may be the probable cause of the higher prevalence of moderate to severe periodontitis found in patients with intestinal diseases. In spite of all the studies, it is necessary to determine a more specific profile between the susceptibility of periodontal disease in relation to patients with intestinal diseases, in order to have the development of effective drugs capable of restoring the fundamental immunological balance to the patient, aiding both in the control of inflammatory periodontal diseases and in inflammatory diseases.