Antioxidant and pro-oxidant activity of Vitamin C in oral environment.

Context: Antioxidant properties and Vitamin C. Background: Vitamin C is a naturally occurring organic compound and a potent antioxidant preventing oxidative damage to lipids and other macromolecules. It can also exhibit bimodal activity as a pro‑oxidant at a higher concentration. Vitamin C has a switch over role from being an antioxidant in physiologic conditions to a pro‑oxidant under pathologic conditions. A systematic review of this role would help to elucidate whether it is an antioxidant or a pro‑oxidant in the oral environment. Objective: To review studies reported in the literature elucidating the activity of Vitamin C and determine whether it is an antioxidant or a pro‑oxidant. Materials and Methods: Articles were searched in PubMed, MEDLINE using appropriate key words like “Vitamin C,” “antioxidant activity,” “pro‑oxidant activity,” “oral health” “oral disease.” Hand search of journals was also performed. Articles were reviewed and analyzed. Results: Search strategy reviewed 10 relevant articles which studied the dual role of Vitamin C. 65% of authors analyzed antioxidant action of ascorbic acid compared to 35% of the pro‑oxidant potential. Vitamin C acts as an antioxidant and a pro‑oxidant by a plethora of mechanisms. Factors determining its bimodal activity were studied, and the frequencies of their occurrence in the literature were depicted in percentage. Conclusion: The data validates the role of Vitamin C as an antioxidant under physiologic conditions exhibiting a cross over role as a pro‑oxidant in pathological conditions. Further studies are required to substantiate its pro‑oxidant activity to draw concrete conclusions.

Citotoxidad de la beta lapachona: una o-naftoquinona con posibles usos terapeuticos / Cytotoxicity of beta-lapachone, an naphthoquinone with possible therapeutic use

La Beta-lapachona (Beta-lap) es una o-naftoquinona extraída de la madera del lapacho. Las observaciones iniciales mostraron su acción inhibidora del crecimiento del sarcoma de Yoshida y del carcinosarcoma de Walker 256. La Beta-lap genera productos reactivos del oxígeno (ROS: anión superóxido, radical hidroxilo y peróxido de hidrógeno) a los que inicialmente se atribuyó su citotoxicidad. Beta-Lap resultó un potente inhibidor de la síntesis de ADN en T. cruzi, de la topoisomerasas I y II y de la poli(ADP-ribosa) polimerasa (PARP) de diferentes orígenes, enzimas responsables de la conservación del ADN. Se investigó la citotoxicidad de Beta-lap en células de cáncer epidermoide de laringe, melanoma, cáncer de ovario, de mama, de próstata, de pulmón, adenocarcinoma de colon y leucemia, aportando un mejor conocimiento de los mecanismos moleculares involucrados en la acción de Beta-lap y su relación con los procesos de apoptosis y de necrosis. Se comprobó la activación de la calpaina, proteasa cuya actividad depende de tioles, seguida por la activación de quinasas (c-JUN NH2 -quinasa terminal), caspasas y nucleasas, enzimas que degradan al ADN y a las proteínas celulares. Una reacción importante para la actividad de la Beta-lap es su reducción, especialmente por la diaforasa y la NAD(P)H-quinona reductasa, que inician la producción de ROS. La acción de Beta-lap sobre células tumorales resultaría de la inhibición directa de enzimas como las topoisomerasas, PARP y el factor TNF, sumada a la acción de radicales libres. Los efectos citostáticos de ß-lap han abierto interesantes perspectivas para la quimioterapia del cáncer.

Reactive oxygen species in health and disease.

With the advent of the use of oxygen as the terminal electron acceptor in aerobic respiration, came the curse in the form of reactive oxygen species (ROS). However, the evolving organism had developed elaborate defence machinery to escape from these reactive byproducts of its own metabolism, and also developed a mechanism for the utilization of these species in physiological processes to gain a survival advantage. ROS have been increasingly implicated in the ageing process and in different diseases such as cancer, Alzheimer's disease, Parkinson's disease, reperfusion injury, etc. They are also important in cellular phenomenon such as signal transduction pathways. We review the mechanisms of production of ROS in the cell, their interaction with cellular macromolecules, pathways of ROS-induced cell death, the mechanisms for protection from ROS-induced damage as well as the key biological and disease processes where ROS play an important role.

Alternative mitochondrial functions in cell physiopathology: beyond ATP production

It is well known that mitochondria are the main site for ATP generation within most tissues. However, mitochondria also participate in a surprising number of alternative activities, including intracellular Ca2+ regulation, thermogenesis and the control of apoptosis. In addition, mitochondria are the main cellular generators of reactive oxygen species, and may trigger necrotic cell death under conditions of oxidative stress. This review concentrates on these alternative mitochondrial functions, and their role in cell physiopathology

Reduçäo no tempo de exposiçäo dos oócitos aos espermatozóides durante a fertilizaçäo in vitro: resultados preliminares / Reducing the time of sperm-oocyte exposure during in vitro fertilization: preliminar results

OBJETIVO: verificar se a reduçäo do tempo de exposiçäo dos oócitos aos espermatozóides in vitro é capaz de melhorar as taxas de fertilizaçäo e clivagem e o desenvolvimento embrionário. PACIENTES E MÉTODOS: foram selecionados 11 casais inférteis submetidos à fertilizaçäo in vitro (FIV) no período de maio a dezembro de 1997. Em cada paciente, uma parte dos oócitos captados foi submetida à FIV convencional (grupo I), e os oócitos restantes foram lavados uma hora após a inseminaçäo, quando também foi realizada a troca do meio de cultura (grupo II). Foram considerados embriöes de boa qualidade (EBQ) aqueles com 4 ou mais células, blastômeros regulares e 50 por cento de fragmentaçäo. RESULTADOS: a taxa de fertilizaçäo foi de 64,8 por cento no grupo I e 59,4 por cento no grupo II (NS). A taxa de clivagem foi de 95,6 por cento no grupo I e de 92,1 por cento no grupo II (NS). Na análise morfológica dos embriöes, verificou-se uma maior proporçäo de EBQ no grupo II (57,1 por cento) em relaçäo ao grupo I (36,9 por cento), com p=0,05. CONCLUSÃO: a reduçäo do temppo de exposiçäo dos oócitos aos espermatozóides in vitro contribui para um melhor desenvolvimento embrionário.

Reactive oxygen species and oxidative DNA damage.

Reactive oxygen species (ROS) such as the superoxide anion radical (O2.-) hydrogen peroxide (H2O2) and hydroxyl radical (.OH) have been implicated in the pathophysiology of various states, including ischemia reperfusion injury, haemorrhagic shock, atherosclerosis, heart failure, acute hypertension and cancer. The free radicals, nitric oxide (NO) and O2.- react to form peroxynitrite (ONOO-), a potent cytotoxic oxidant. A potential mechanism of oxidative damage is the nitration of tyrosine residues of protein, peroxidation of lipids, degradation of DNA and oligonucleosomal fragments. Several mechanisms are responsible for the protection of the cells from potential cytotoxic damage caused by free radicals. Cells have developed various enzymatic and nonenzymatic defense systems to control excited oxygen species, however, a certain fraction escapes the cellular defense and may cause permanent or transient damage to nucleic acids within the cells, leading to such events as DNA strand breakage and disruption of Ca2+ metabolism. There is currently great interest in the possible role of ROS in causing DNA damage that leads to cancer and spontaneous mutations. A high rate of oxidative damage to mammalian DNA has been demonstrated by measuring oxidized DNA bases excreted in urine after DNA repair. The rate of oxidative DNA damage is directly related to the metabolic rate and inversely related to life span of the organism.

Efectos fisiopatologicos del oxido nitrico y su relacion con el estres oxidativo / Psysiopathologic effects of nitric oxide and its relationship with oxidative stress

El óxido nítrico (NO.) es producido por la oxidación de la arginina a citrulina, una reacción catalizada por las enzimas óxido nítrico sintasas (NOS). Se acepta que esa reacción es la única capaz de producir NO en los sistemas biológicos, en condiciones normales o patológicas. El NO regula diferentes funciones en células y tejidos de mamíferos, tales como: (a) el control de la presión sanguínea; (b) la relajación del tono del músculo liso arterial; (c) la agregación y adhesión plaquetaria; (d) la neurotransmisión; (e) la función neuro-endócrina. El NO. también participa en la destrucción de microorganismos patógenos y de células tumorales por leucocitos y macrófagos. La producción de anión superóxido (O2-) y NO. ha sido asociada al desarrollo de muchas patologías, pero recientemente se ha comprobado que la interacción de esas moléculas genera el ión peroxintrito (ONOO-), lo que constituye un importante mecanismo fisiopatológico pues, como oxidante, el ONOO- ataca un gran número de blancos biológicos. Por su influencia sobre la producción de ONOO-, el balance entre la producción de NO y O2- es crítico en la etiología de procesos como hipertensión, ateroesclerosis, enfermedades neurodegenerativas, infecciones virales, daño por isquemia-reperfusión y cáncer.

Biochemical aspects of cellular antioxidant systems

Aerobic life is characterized by a steady generation of reactive oxygen species balanced by a similar rate of their consumption by antioxidants. To maintain homeostasis, there is a requirement for the continuous regeneration of antioxidant capacity, and if this is not met, oxidative stress occurs, resulting in pathophysiological events. Cellular protection against oxidative stress is organized at multiple levels. Defense strategies include prevention, interception, replacement, and repair. These mechanisms are coupled to the intermediary metabolism for a continuous supply of energy, reducing equivalents, and precursors, and depend on the dietary supply of metabolic fuels and essential molecules to allow an optimal cellular functioning