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Oxidative Cellular Damage

Oxidative cellular damage

Oxidative Cellular Damage 


 1. Re, S. Barocci, L. Rinaldi, C. Vivani, A. Scucimarra and G. Paolucci

Since many years the role of reactive oxygen species  (ROS) in the acute and chronic diseases  represented  the  topic  of  numerous  scientific  papers.  Indeed,  the  oxidative cellular damage to DNA, RNA, protein and cell membranes that physiologically occurs during the ageing process and the partial protection exerted by the cell defence systems represent well-known processes. On the other hand, in various pathological conditions the main problem is related to a rapid increase in the cellular ROS concentration that exceeds the capacity of the cell to eliminate them. Normally, ROS derived from the oxygen reduction during  the  biochemical  pathways  of  the  cell  energy  production  systems (Gershman, Science, 119: 623-626, 1954).

In some pathological conditions ROS could increase either for a primitive defect of the cell defence system or following an overproductions derived either from the cell death or apoptosis phenomena. Nevertheless, the role of the oxidative stress  in  the  induction  of  apoptosis  is  well  known  and  the  oxidation  of  glutathione represents  an  early  event  in  the  course  of  apoptosis.  Recent  data  dealt  on  the  pro-oxidative activity of CuZn superoxide dismutase (SOD) and nitroxide SOD-mimics. SOD is unique in being present in cells and in various experimental systems in a concentration excess over its substrate. If the enzyme or its mimics are present in the oxidized form, they may oxidize various cellular or exogenous substrates  (Offer et al, FASEB J,  14(9): 1215-23,  2000). The natural defenses against ROS could be classified as exogenous or endogenous. The first ones, diet dependent, comprise vitamins, E and C, flavonoids and polyphenols while SOD, glutathione peroxidase, catalases are being considered the main endogenous species. The first hypothesis of a positive conditioning induced by low ozone .concentrations against the oxidative stress has been recently proposed by Leon Fernandez et al (Int. Cong. Pharmacol., CPT 2000, Florence, Brit J Clin Pharmaco, July 15-20, 2000).

The theory is based upon the fact the low, non-toxic, ozone doses could raise the efficacy of the endogenous system by increasing the production or the activity of some antioxidant enzymes  isoforms.  Looking  at  the  ischaemic  preconditioning  in  which  is  scientifically proved that repetitive brief ischaemia plays an important role in the acquisition of late-phase cardioprotection against ischaemia/reperfusion injury in rats (Yamashita et al, Br J Pharmacol, 131(3): 415-422, 2000), we can speculate that repetitive brief oxidative stress induced with low ozone doses could  ameliorate  the cell defense mechanisms against ROS. The hypothesis is supported by other data reported by Rao and Shaha (Free Radic Biol Med, Nov  15;  29  (10):  1015-1027,  2000) demonstrating the formation of multiple isoforms of glutathione S-transferase after the exposure to H2O2.

A further evidence of the protective action induced by low ozone concentrations has been proposed by our group (Re et al, Gen Pharmacol,  32; 245-250, 1999). Indeed, we proved the reduction of the intracellular calcium at presynaptic levels after the exposure to low ozone doses.  The cytosolic  calcium  could  be  considered  as  the  common  final  pathway  of  the  cellular damage, either physiologically or pathologically. A low calcium level represents a further element  in  supporting  the  idea  of  the  oxidative  cell  damage  protection  either  in  the chronic or in the acute ageing. We think that the use of ozone in the medical field could represents a useful and safety therapeutic potential in many pathologies actually orphan of adequate pharmacological treatment and in the prevention of the naturally occurring ageing.

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