Antioxidant Activity of Fraxetin: In Vivo and ex Vivo Parameters in Normal Situation versus Induced Stress.

Abstract

Free radicals generation during cellular metabolism is the main cause of molecular damage underlying the aging process.1) Several authors assert that induced stress enhanced this process, because the deleterious effects of free radicals are progressive and accumulative. [2][3][4] The effect of free radicals in the Drosophila melanogaster life span has been amply studied. 5,6) Various authors have demonstrated a decrease in negative geotaxis in aging, so microgravity is an adequate measure of the vital capacity of flies. [7][8][9] This investigation establishes the influence of stress provoked by the assay of microgravity (flying capacity reduction) in the life span of flies. Therefore, we have evaluated the survival values of the population submitted to an assay of microgravity during its development until the death of the last individual.Their life expectancy is relative to their basal metabolic rate 10) and can be altered by diet, temperature, light and exposure to antioxidants. These conditions affect the level of free radicals.11) The effects of exogenous antioxidant administration on the prevention of diseases was proposed by Gerschman,12) and these beneficial effects could influence the life span.13) This study examined the effect of the exogenous administration of a natural product, such as Fraxetin, on the life span of Drosophila melanogaster, and on its vital capacity.On the other hand, we evaluated the biochemical parameters associated with the free radical theory. Reduced forms of glutathione are capable of reducing various free radicals, 14) so the oxidative status could be evaluated by measuring this natural antioxidant. Another parameter affected by the induced stress is lipid peroxidation. An increase in lipid peroxides is usually taken as an estimator of oxidative stress. 15,16) So, both parameters could establish oxidative status, but an increase in GSH content does not always correspond with the decrease in lipid peroxidation, since both parameters can be produced by different mechanisms. This feature indicates the complex mechanisms implicated in oxidative stress. MATERIALS AND METHODS AnimalsOregon R Drosophila fruit flies were maintained in an environmentally controlled incubator at 25°C on a 12/12 h light/dark cycle, with constant humidity. Flies were fed a free PUFA diet, based on an agar (1.1%) culture medium containing sugar (7.5%), corn flour (3.5%) and the yeast Sacharomyces cerevisiae (7.5%). The treatment was introduced in the daily diet at different ages of the animal model, following the model proposed by Miquel. 17) In the case of the treatment groups, Fraxetin was directly incorporated on the culture medium, so the culture medium of the treatment groups was homogenous concentration of 1 mM of Fraxetin. We did not use an organic solvent to solve Fraxetin, and there was no influence of solvents on oxidative stress or life span in our research. The treatment groups were the Control (without treatment, as comparation), F-0 (Fraxetin treatment from the 1st day, 1 mM), F-1 (Fraxetin ...

Bone Morphogenetic Protein-2 and -4 (BMP-2 and -4) Mediates Fraxetin-Induced Maturation and Differentiation in Human Osteoblast-Like Cell Lines

“…15,16) Fraxetin (7,8-dihydroxy-6-methoxy coumarin), a coumarin derivative, has been reported to possess antioxidative, antiinflammatory and neuroprotective effects. [17][18][19][20][21][22] Fraxetin exhibits it anti-inflammatory effect through inhibiting the formation of the 5-lipoxygenase product, 5-HETE, and the cyclooxygenase product, HHT. 18) In addition, a previous studies report that some coumarin derivatives include fraxetin, is able to protect neuroblastoma cells against toxic effects induced by rotenone.…”

Synthetic and Natural Coumarins as Antioxidants

“…The aim of the paper of Fernandez-Puntero et al [24] was to study the influence of fraxetin (7,8-dihydroxy-6-methoxycoumarin) (1 3 ) treatment in a Drosophila melanogaster experimental model, analyzing several parameters in normal situations and instances of induced oxidative stress. Fraxetin treatment was introduced at different ages.…”

Fraxetin inhibits the induction of anti-Fas IgM, tumor necrosis factor-α and interleukin-1β-mediated apoptosis by Fas pathway inhibition in human osteoblastic cell line MG-63

“…Moreover, excessive amounts of other cytokines, International Immunopharmacology 6 (2006) 1167 -1175 www.elsevier.com/locate/intimp including TNF-α and IL-1β, have also been detected in inflamed synovium, which also indicates that interaction between TNF-α, IL-1β and FasL augments the apoptosis of osteoblast cells, resulting in loss of bone mass [10,11]. Fraxetin (7,8-dihydroxy-6-methoxv coumarin), a coumarin derivative, has been reported to possess antioxidative, anti-inflammatory and neuroprotective effects [12][13][14][15][16]. Fraxetin exhibits its anti-inflammatory effect through inhibiting the formation of the 5-lipoxygenase product, 5-HETE, and the cyclooxygenase product, HHT [16].…”