The role of mitochondrial DNA damage in the citotoxicity of reactive oxygen species.

Mitochondria contain their own genome, a small circular molecule of around 16.5 kbases. The mitochondrial DNA (mtDNA) encodes for only 13 polypeptides, but its integrity is essential for mitochondrial function, as all 13 proteins are regulatory subunits of the oxidative phosphorylation complexes. Nonetheless, the mtDNA is physically associated with the inner mitochondrial membrane, where the majority of the cellular reactive oxygen species are generated. In fact, the mitochondrial DNA accumulates high levels of oxidized lesions, which have been associated with several pathological and degenerative processes. The cellular responses to nuclear DNA damage have been extensively studied, but so far little is known about the functional outcome and cellular responses to mtDNA damage. In this review we will discuss the mechanisms that lead to damage accumulation and the in vitro models we are establishing to dissect the cellular responses to oxidative damage in the mtDNA and to sort out the differential cellular consequences of accumulation of damage in each cellular genome, the nuclear and the mitochondrial genome.

Topical anti-inflammatory effect of Caryocar coriaceum Wittm. (Caryocaraceae) fruit pulp fixed oil on mice ear edema induced by different irritant agents.

AIM OF THE STUDY: Caryocar coriaceum Wittm. fruit pulp fixed oil (CCFO) has been widely employed by communities from Brazil Northeastern in the treatment of skin inflammation, respiratory affections, wound healing and muscle pain. In this study, we evaluated the topical effect of CCFO against different irritant agents in vivo, in order to verify its antiedematous effect as well to unravel its tentative mechanisms of action. MATERIALS AND METHODS: CCFO was obtained from Caryocar coriaceum fruits using ethyl acetate as solvent. Ear edema provoked by the application of Croton oil (single and multiple applications), arachidonic acid (AA), capsaicin, phenol and histamine to Swiss mice was used to evaluate the topical anti-inflammatory effect of CCFO. Histological analysis from mice ears sensitized with Croton oil and AA single application was also performed. RESULTS: Crude CCFO (20µL/ear) demonstrated significant topical antiedematous effect against Croton oil single (inhibition of 32.0%; P<0.05) and multiple (41.4% after 9 days, P<0.001) applications, AA (inhibition of 49.7%; P<0.01) and phenol (inhibition of 38.8%; P<0.001). In contrast, CCFO did not antagonize the edema caused by topical treatment with capsaicin and histamine when compared to control group (P>0.05). Histological analysis also revealed that CCFO was able to reduce the edema and the influx of inflammatory cells in mice ears sensitized with Croton oil and AA. CONCLUSIONS: CCFO exhibited a similar profile of topical anti-inflammatory activity to that of drugs that classically modulate the production of arachidonic acid metabolites. The study also indicates the potential application of CCFO as an important herbal medicine to be used against skin inflammatory diseases.

[Relationship between coronary artery disease and periodontal disease. What the cardiologist must know]. / Relations entre les pathologies cardiovasculaires et buccodentaires. Ce que le cardiologue doit connaître.

In this review, we will present the recent works, which shows a link between arterial lesions, particularly in coronary arteries, and periodontal disease. The pathways are those of chronic infection, and several studies have revealed a relationship between arterial lesions and buccal bacteraemia. Though the mechanism that links them is still unclear, the first hypotheses suggest that the presence of the bacteria in the bloodstream triggers a direct reaction (bacteria on the target organ), and/or an indirect immune reaction. This immune response could be induced by an increase in the secretion of pro-inflammatory cytokines (IL1, IL6, TNF), which are also involved in atherogenesis. Indeed, these cytokines have been found in higher concentrations in patients with periodontal disease, whereas reduced levels have been found in patients who have had deep gum pockets thoroughly cleaned. Cardiologists need to have access to such information not only because of the similarity of the populations, but also because of the therapeutic consequences. The future development of simple dental scores will provide an important tool for epidemiological studies of primary and secondary prevention.