Oxidative stress, antioxidant defences and aging

Abstract

Apoptosis and aging share common mechanisms in oxidative stress and mitochondrial involvement. Treatment of cultured neuroblastoma cells with a radical initiator induced apoptosis; raise in hydrogen peroxide and release of cytochrome c from mitochondria preceded collapse of mitochondrial potential and cell death. In rat hepatocytes treated with adriamycin incubation with exogenous Coenzyme Q10 counteracted the drug-induced increase of hydrogen peroxide and the fall of the mitochondrial potential, thus demonstrating the quinone antioxidant effect. Complex I activity and its rotenone sensitivity decreased in brain cortex non-synaptic mitochondria from old rats; a 5 kb mitochondrial DNA deletion was found only in the old rats. A similar behavior was found in human platelets from old individuals. The postulated energy decline was confirmed by the inhibitor sensitivities of platelet aggregation and lactate production. The lack of the 5 kb deletion in platelets throws doubts on mitochondrial DNA lesions as the only causes of mitochondrial dysfunction in aging.

Coenzyme Q10 Prevents Apoptosis by Inhibiting Mitochondrial Depolarization Independently of Its Free Radical Scavenging Property

“…We demonstrated that a 2-h pretreatment with CoQ 10 lowered the number of apoptotic keratocytes in response to excimer laser irradiation to a much higher extent than other free radical scavengers both in vitro (6) and in vivo (5). The antiapoptotic effects of CoQ 10 as free radical scavenger have been demonstrated consistently by others (2,(7)(8)(9)(10)(11) in parallel or in successive works.…”

“…doreductase), II (succinate-ubiquinone oxidoreductase), and III (ubiquinone-cytochrome c oxidoreductase) of mitochondrial respiratory chain and a ubiquitous free radical scavenger (1,2). Our preliminary observations that CoQ 10 is endowed with antiapoptotic activity as a free radical scavenger (3) prompted us to challenge the ability of CoQ 10 to prevent keratocyte apoptosis induced by excimer laser photorefractive keratectomy.…”

Deferiprone protects the isolated atria from cardiotoxicity induced by doxorubicin

“…This affinity results in the accumulation of DOX in cardiac myocytes with higher concentrations than that in other cells [25] , and causes oxidative damage on mitochondrial membranes, the respiratory chain, and DNA [26][27][28] . On the other hand, the mitochondrial respiratory chain is the major source of superoxide, thus, mitochondria are more susceptible to oxidative damage than the rest of the cells [29] . SDH is a component of complex II of the respiratory chain and is the only tricarboxylic acid cycle enzyme embedded to the inner mitochondrial membrane that is essential for full respiratory activity.…”

Natural compounds, fraxin and chemicals structurally related to fraxin protect cells from oxidative stress

“…Differential display RT-PCR revealed that fraxin upregulated anti-apoptotic genes (clusterin and apoptosis inhibitor 5) and tumor suppressor gene (ST13). This finding is interesting that fraxin induced anti-apoptotic genes (Wolf and Green, 2002;Thiede and Rudel, 2004) because apoptosis and aging share common mechanisms in oxidative stress and mitochondrial involvement (Lenaz et al, 1998). Cells in the brain deploy multiple mechanisms to maintain the integrity of nerve cell circuits, and to facilitate responses to environmental demands and promote recovery of function after injury (McGeer et al, 1992).…”