Abstract Curcumin (CMN) is the principal active component derived from the rhizome of Curcuma longa (Curcuma longa L.). It is a liposoluble polyphenolic compound that possesses great therapeutic potential. Its clinical application is, however, limited by the low concentrations detected following oral administration. One key strategy for improving the solubility and bioavailability of poorly water-soluble drugs is solid dispersion, though it is not known whether this technique might influence the pharmacological effects of CMN. Thus, in this study, we aimed to evaluate the antioxidant and antigenotoxic effects of CMN formulated in a solid dispersion (CMN SD) compared to unmodified CMN delivered to Wistar rats. Cisplatin (cDDP) was used as the damage-inducing agent in these evaluations. The comet assay results showed that CMN SD was not able to reduce the formation of cDDP-DNA crosslinks, but it decreased the formation of micronuclei induced by cDDP and attenuated cDDP-induced oxidative stress. Furthermore, at a dose of 50 mg/kg b.w. both CMN SD and unmodified CMN increased the expression of Tp53 mRNA. Our results showed that CMN SD did not alter the antigenotoxic effects observed for unmodified CMN and showed effects similar to those of unmodified CMN for all of the parameters evaluated. In conclusion, CMN SD maintained the protective effects of unmodified CMN with the advantage of being chemically water soluble, with maximization of absorption in the gastrointestinal tract. Thus, the optimization of the physical and chemical properties of CMN SD may increase the potential for the therapeutic use of curcumin.

O uso da dapsona é frequentemente associado a efeitos adversos hematológicos, como a metemoglobinemia e anemia hemolítica, ambos relacionados com a N-hidroxilação mediada pelo sistema P450. O objetivo do estudo foi avaliar a influência da suplementação de L-arginina, um precursor da síntese de óxido nítrico, administrado em regime de dose única ou múltipla na metemoglobinemia induzida pela dapsona. Ratos machos Wistar foram tratados com L-arginina (po, gavagem) em dose única ou múltipla de 5, 15, 30, 60 e 180 mg/kg 2 horas antes da administração de dapsona (40 mg/kg, ip). O efeito do L-NAME, um inibidor de óxido nítrico sintase (NOS), foi avaliado através do tratamento com doses múltiplas de 30 mg/kg. Amostras de sangue foram coletadas duas horas após a administração de dapsona. A concentração de metemoglobina eritrocitária foi analisada por espectrofotometria. Os resultados mostraram que a suplementação em dose múltipla de 5 e 15 mg/kg de L-arginina reduziu os níveis de metemoglobina induzida pela dapsona. Este efeito é mediado pela formação de óxido nítrico, uma vez que a redução nos níveis de metemoglobina pela L-arginina é bloqueada pela administração simultânea de L-NAME, um inibidor da óxido nítrico sintase.

Dapsone use is frequently associated to hematological side effects such as methemoglobinemia and hemolytic anemia, which are related to N-hydroxylation mediated by the P450 enzyme system. The aim of the present study was to evaluate the influence of L-arginine supplementation, a precursor for the synthesis of nitric oxide, as single or multiple dose regimens on dapsone-induced methemoglobinemia. Male Wistar rats were treated with L-arginine at 5, 15, 30, 60 and 180 mg/kg doses (p.o., gavage) in single or multiple dose regimens 2 hours prior to dapsone administration (40 mg/kg, i.p.). The effect of the nitric oxide synthase inhibitor L-NAME was investigated by treatment with multiple doses of 30 mg/kg (p.o., gavage) 2 hours before dapsone administration. Blood samples were collected 2 hours after dapsone administration. Erythrocytic methemoglobin levels were assayed by spectrophotometry. The results showed that multiple dose supplementations with 5 and 15 mg/kg L-arginine reduced dapsone-induced methemoglobin levels. This effect is mediated by nitric oxide formation, since the reduction in methemoglobin levels by L-arginine is blocked by simultaneous administration with L-NAME, a nitric oxide synthase inhibitor.

De acordo com estudos clínicos e pré-clínicos, o estresse oxidativo e suas conseqüências podem ser a causa, ou, no mínimo, o fator que contribui para grande número de doenças degenerativas. Estas doenças incluem problemas comuns e debilitantes, caracterizados por perda progressiva e irreversível de neurônios em regiões específicas do cérebro. As doenças degenerativas mais comuns são doença de Parkinson, de Hutington, de Alzheimer e esclerose amiotrófica lateral. A Coenzima Q10 (CoQ10) tem sido intensamente estudada desde sua descoberta, em 1957. É um componente da cadeia de transporte eletrônico e participa da respiração aeróbica celular, gerando energia na forma de trifosfato de adenosina (ATP). A propriedade da CoQ10 de atuar como antioxidante ou pró-oxidante sugere papel importante na modulação do estado redox celular sob condições fisiológicas e patológicas, desempenhando, também, papel no processo de envelhecimento. Em vários modelos animais de doenças neurodegenerativas, a CoQ10 mostrou efeitos benéficos na redução do curso da doença. Entretanto, há necessidade de estudos adicionais para avaliar o efeito e a eficácia da CoQ10 antes de expor os pacientes a riscos de saúde desnecessários e de alto custo.

According to clinical and pre-clinical studies, oxidative stress and its consequences may be the cause or, at least, a contributing factor, to a large number of neurodegenerative diseases. These diseases include common and debilitating disorders, characterized by progressive and irreversible loss of neurons in specific regions of the brain. The most common neurodegenerative diseases are Parkinson's disease, Huntington's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Coenzyme Q10 (CoQ10) has been extensively studied since its discovery in 1957. It is a component of the electron transportation chain and participates in aerobic cellular respiration, generating energy in the form of adenosine triphosphate (ATP). The property of CoQ10 to act as an antioxidant or a pro-oxidant, suggests that it also plays an important role in the modulation of redox cellular status under physiological and pathological conditions, also performing a role in the ageing process. In several animal models of neurodegenerative diseases, CoQ10 has shown beneficial effects in reducing disease progression. However, further studies are needed to assess the outcome and effectiveness of CoQ10 before exposing patients to unnecessary health risks at significant costs.

Polyphenols are potent antioxidants that are particularly abundant in the Mediterranean diet, with olive oil being the main fat source. A number of investigations have reported that phenolic compounds found in dietary oils are antioxidants and could provide protective effects by inhibiting DNA oxidative damage. However, few studies have been published on the biological activity of vegetable oils, including their possible mutagenic/antimutagenic effects. The objective of the current study was to investigate the cytogenetic effects of multiple doses of four vegetable oils in rat bone marrow cells and to examine the possible antimutagenic effects of these oils in chromosomal damage induced by the antitumor drug cisplatin. These oils are consumed by humans and commonly used as drug vehicles. The rats received treatment with multiple doses of canola oil, olive oil, virgin olive oil, and corn oil (5 mL kg-1) alone or combined with the antitumor drug cisplatin (5 mg kg-1). Treatments with vegetable oils alone did not increase the percentage of cells with chromosomal aberrations (p > 0.05). Olive, virgin olive and canola oils showed protective effects against cisplatin-induced chromosomal damage (p < 0.05). A rational mechanism for the protective effects of vegetable oils is that their phenolic compounds have antioxidant and antimutagenic properties in vivo.

A cisplatina é uma droga antineoplásica altamente efetiva contra vários tipos de cânceres humanos, tais como tumores do testículo e ovário, câncer da cabeça e pescoço e câncer do pulmão. Entretanto, a nefrotoxicidade é um dos principais efeitos colaterais da terapia com a cisplatina. A gravidade da nefrotoxicidade induzida pela cisplatina está relacionada com a concentração de platina nos rins. As evidências mostram que a nefrotoxicidade induzida pela cisplatina é atribuída ao dano oxidativo resultante da geração de radicais livres, e que a administração de antioxidantes é eficiente na inibição destes efeitos colaterais. Uma abordagem alternativa para proteger os roedores dos efeitos colaterais da cisplatina é o uso de conhecidos antioxidantes da dieta. Alguns estudos têm sido realizados para diminuir a peroxidação lipídica e os efeitos citotóxicos induzidos pela cisplatina, com o emprego de antioxidantes da dieta, tais como, selenito de sódio, vitaminas C e E, curcumina e o carotenóide bixina. Nós sugerimos que aqueles antioxidantes da dieta têm efeito nefroprotetor, e que os mecanismos antioxidantes destes compostos deveriam ser explorados durante a quimioterapia com a cisplatina.

Cisplatin is a highly effective antineoplastic drug used against several types of human cancers, such as testicular and ovarian tumors; head and neck; and lung cancer. However, nephrotoxicity is one of the most important side-effects of cisplatin therapy. The severity of cisplatin nephrotoxicity is related to platinum concentration in the kidneys. There is a growing amount of evidence that cisplatin-induced nephrotoxicity is ascribed to oxidative damage resulting from free radical generation and that the administration of antioxidants is efficient in inhibiting these side effects. An alternative approach aiming to protect rodents against cisplatin side-effects is the introduction of known dietary antioxidants. Some studies have been conducted to decrease cisplatin-induced lipid peroxidation and cytotoxic effects by using such dietary antioxidants, including sodium selenite; vitamins C and E; curcumin and the carotenoid bixin. We suggest that these dietary antioxidants have a nephroprotective effect, and that their antioxidant mechanisms should be further explored during cisplatin chemotherapy.

Cientometria é definida como o estudo da mensuração e quantificação do progresso científico, estando a pesquisa baseada em indicadores bibliométricos. A cientometria tem um grande potencial de aplicação, havendo interesse de Governos e instituições de pesquisas em utilizar este conhecimento com o objetivo de implementar diferentes formas de apoio ao desenvolvimento científico e tecnológico. Nos últimos tempos, também, ela tem sido usada para ajudar nações a tomarem decisões sobre quais áreas do saber necessitam de fundos especiais; além disso, a análise das citações ou dos fatores de impacto de periódicos e artigos vem se tornando uma fonte importante de informação para historiadores, sociólogos e outros pesquisadores interessados na evolução da ciência. Este artigo focaliza como diferentes indicadores de citação tornam possível verificar tanto a evolução das descobertas quanto o impacto do trabalho publicado. Esta análise quantitativa complementa as opiniões e os julgamentos realizados por especialistas (avaliação pelos pares), fornecendo instrumentos úteis e objetivos para avaliar os resultados da atividade científica.

Scientometrics is defined as the study of the measurement and quantification of scientific and technological progress and much the research is bibliometric in nature. Scientometric has a wide potential applicability. Government and research institutions have expressed interest in applying this knowledge of scientific growth to the management of science.. Ultimately, scientometrics may be used to help nations make decisions on what areas of research need funding. The citation analyses have become an increasingly significant source of information for historians, sociologists, and other researchers studying the evolution of science. This article focuses on how citation indexes make it possible to trace the background and development of discoveries as well as to assess the credit that publishing scientists assign to particular discoverers. This kind of analysis complements the opinions and judgments of experts (peer review), thus providing objective and useful tools for evaluating the results of scientific activity.

Foram comparados o estado nutricional e parâmetros do metabolismo do ferro de adultos HIV-positivos, com ou sem resposta de fase aguda (RFA). Adultos HIV-positivos (n = 29) submeteram-se a antropometria, recordatório alimentar e determinação sérica de albumina, proteína C reativa (PCR), ferritina e capacidade total de ligação do ferro (CTLF), além de creatinina urinária. Infecção mais PCR > 7mg/dl foram critérios de positividade da RFA. Índice de massa corporal (IMC < 18,5kg/m2) e índice creatinina-altura (ICA < 70%) definiram subnutrição. Subnutrição (77,8 vs 40%) e tuberculose pulmonar (44,4 vs 9,5%) foram mais freqüentes nos pacientes RFA-positivos, que também apresentaram menores níveis de albumina (3,7 ± 0,9 vs 4,3 ± 0,9g/dl), CTLF (165,8 ± 110,7 vs 265,9 ± 74,6mg/dl) e hemoglobina (10,5± 1,8 vs 12,6 ± 2,3g/dl). A ingestão de ferro foi adequada e similar entre RFA-positivos e RFA-negativos, o mesmo ocorrendo, respectivamente, quanto à ferritina sérica (mediana; variação, 568; 45,3-1814 vs 246; 18,4-1577ng/ml). Pacientes HIV-positivos com resposta de fase aguda são nutricionalmente mais comprometidos e têm anemia que parece não depender da ingestão recente de ferro.

Nutritional status and some iron metabolism parameters of acute phase response (APR) positive and APR-negative AIDS patients were studied. Twenty-nine AIDS patients were submitted to 24h food intake recall, anthropometry, and albumin, C-reactive protein (CRP), hemoglobin, ferritin, and total iron binding capacity (TIBC) measurements. Infection plus serum CRP > 7mg/dl were criteria for APR presence. Protein-energy malnutrition (PEM) was ascertained by body mass index (BMI) lower than 18.5kg/m2 and height-creatinine index (HCI < 70%). PEM (77.8 vs 40%) and pulmonary tuberculosis (44.4 vs 9.5%) were more frequent in APR-positive patients, which also had lower serum albumin (3.7 ± 0.9 vs 4.3 ± 0.9g/dl), TIBC (165.8 ± 110.7 vs 265.9 ± 74.6mg/dl) and blood hemoglobin (10.5 ± 1.8 vs 12.6 ± 2.3g/dl). Iron intake was similar between groups; however, serum ferritin levels (median, range) were higher among APR-positive (568, 45.3-1814 vs 246, 18.4-1577ng/ml) patients. HIV-positive adults with systemic response to invading pathogens showed worse nutritional status than those APR-negative. In APR-positive AIDS patients, anemia appears to be unrelated to recent iron intake.

Durante a redução do oxigênio molecular, espécies reativas de oxigênio são formadas e existe a necessidade permanente de inativar estes radicais livres. Os danos induzidos pelos radicais livres podem afetar muitas moléculas biológicas, incluindo os lipídeos, as proteínas, os carboidratos e as vitaminas presentes nos alimentos. As espécies reativas de oxigênio também estão implicadas nas várias doenças humanas. Evidências têm sido acumuladas indicando que uma dieta rica em antioxidantes reduz os riscos das principais doenças humanas. Esta revisão discute a importância dos antioxidantes da dieta sobre as estratégias de defesa dos organismos contra os radicais livres.

During the reduction of molecular oxygen, reactive oxygen species are formed and there is a continuous requirement for inactivation of these free radicals. Damage induced by free radicals can affect many biological molecules, including lipids, proteins, carbohydrates and vitamins present in the food. Reactive oxygen species are also thought to be implicated in the pathogenesis of various human diseases. In fact, evidence has been accumulated indicating that a diet rich in antioxidants reduce the risks of the major human diseases. This review discusses the importance of dietary antioxidants in the defense strategies of organisms against free radicals.