Free radicals. Their effects on biomolecular structures and human health

Abstract

Free radicals are chemical species that have one ormore unpaired electrons in themost distal orbital of some of their components (usually oxygen or nitrogen). They have a variable electronic charge thatmay be neutral, electropositive or electronegative. The free radicalsmost extensively researched are those containing oxygen which, together with various oxygenated compounds that have no direct action as free radicals but thatmay lead to their formation, are included among the so called “reactive oxygen species” (ROS). Free radicals have a very high chemical reactivity since they avidly seek to acquire the electron which they are lacking fromother compounds. Generally speaking, the simpler themolecular structure of a free radical, the shorter its life. Radicals of this type are formed in a wide variety of situations and their effectsmay be beneficial or harmful to our body. The beneficial effects include their participation in our defencemechanisms, allowing themost important phagocytic white blood cells or leukocytes to formone of themost powerful bactericides, hypochlorite (the basis of lye);moreover, certain reactive oxygen species play a fundamental role in the activation of the pathways involved in the synthesis of prostaglandins, thromboxanes and leukotrienes. Free radicals are also involved in processes that have undesirable effects on our organism, however, due to their toxicity. Theymay help to change various types of biomolecules, disrupting the normal functioning of many of the body’s systems and consequently affecting the individual’s functional capacity. The reactive oxygen species,which include free radicals,may affect carbohydrates (altering the the immune system), proteins (disrupting the normal functioning of the transport systems and the cellular signalling processes), polyunsaturated fatty acids (modifying the characteristics of cellmembranes or the outer cover of lipoproteins), and nucleic acids (with the danger of inducingmutations in the genetic code), among other substances. Fromthe clinical standpoint, free radicals are connected with the development and progression of a significant set of disorders that range fromr heumatoid arthritis through senile macular degeneration, cataracts, post-ischaemic complications, etc. to cardiovascular shock. In relation to these conditions, this paper gives a detailed description of the involvement of free radicals in the ischaemia/reperfusion processes, in the autooxidation of homocysteine and its role in atherosclerosis, in the development and progression of cataracts and of senile macular degeneration and their effects on visual capacity, in the oxidation of polyunsaturated fatty acids with the consequent effects on low density lipoproteins (LDL) and the subsequent involvement in the atheromatous process, and in the disruption of some of the components of nucleic acids (mainly deoxyribonucleic acid) thatmay lead to isolated changes ormutations. Due to the peculiar characteristics of free radicals and, generally, of the reactive oxygen species, our body has developed various strategies addressed to protecting itself against their effects. A substantial number of proteins and smallmolecules participate in the defence of our organism against the aggressive action of the toxic derivatives of oxygen, forming what are called antioxidants or antioxidant systems. Two types of antioxidantsmay be distinguished: a) The blocking or neutralizing type, of non-enzymatic character,which prevents the chain-reaction propagation of the oxidation processes. The antioxidants of this type are substances that are easily oxidable and that act by providing a hydrogen atomwhich contains a single electron in its orbital, adding it to the orbital of the radical that has an unpaired electron. This group includes the carotenoids, vitamins C and E, bilirubin, glutathione, cysteine, uric acid, etc. b) The preventive type,which reduces the formation of free radicals by breaking down some of their precursors. The antioxidant systems of this type transformfree radicals intomolecular structures that are less or not at all aggressive, mainly comprising enzymatic systems that are present in the various cells of our body. This group includes the superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase. Plants are a very important source of antioxidants as they synthesize hundreds of different compounds aimed to protect them fromthe harmful effects of the free radicals generated in the processes associated with photosynthesis. All these phytochemical compounds have very similarmolecular structures which nevertheless show a great chemical diversity due to the need to adapt to different environments and circumstances and to protect plants against the effects of a very broad variety of free radicals.

KEYWORDS: reactive oxygen species, free radicals, oxidation, prooxidants, antioxidants.