THE MULTIFACED ROLE OF OXIDATIVE STRESS: FROM APOPTOSIS TRIGGERING TO ACTIVATION OF CELLULAR DEFENSES

Alberto IZZOTTI

(Genoa, Italy)

THE MULTIFACED ROLE OF OXIDATIVE STRESS: FROM APOPTOSIS TRIGGERING TO ACTIVATION OF CELLULAR DEFENSES

11:30 AM 22 April / Nisan 2018

Abstract

Since many time oxidative stress has been envisaged as a pathway damaging intracellular structures and contributing to the arising of chronic degenerative diseases. Indeed high levels of oxidative damage can be detected in target organs of cardiovascular diseases (arteries, heart) and ocular disease (cataract, glaucoma). Dealing cancer, oxidative stress is a recognized promoter of cancer development, as demonstrated in experimental animal models of lung and skin carcinogenesis and in human carcinogenesis induced by cigarette smoke. However, recent evidences indicate that oxidative stress has a multi-faced role depending on its level and on the type of targeted tissue. Oxidative stress at low level activates cellular defense against toxic agents as well as against high levels of oxidative stress, a situation referred to as ‘hormesis’. Oxidative stress at low level is able to destroy bacteria thus exerting disinfectant activity, especially towards anaerobic and Gram negative bacteria. At the same time, oxidative stress activates wound healing pathways and inhibit macrophage activation thus exerting anti-inflammatory activity. These mechanisms can be used to cure skin wounds and ulcers. Cancer cells, with particular reference to cancer stem cells, are highly vulnerable to oxidative stress as demonstrated by the fact that many anti-cancer drugs are potent intracellular oxidants (e.g., ionizing radiation, anthracyclines). Cancer cells block the main endogenous source of oxidative stress, the mitochondrion, thus blocking the intrinsic pathway of apoptosis activation, a situation referred to as Warburg effect. Based on these premises, oxidative stress as exerted by lipohilic agents could be proposed to kill cancer cells as a complementary tool to standard radio/chemotherapies.

These considerations, indicate that nowadays oxidative stress has a recognized multi-tasking role its biological consequences depending on both dose and cellular target. Oxidative stress cannot be any more considered only a damage-inducing mechanism but, under certain circumstances, as a therapeutic tool.