Could Polyphenols Really Be a Good Radioprotective Strategy?

Abstract

Currently, radiotherapy is one of the most effective strategies to treat cancer. However, deleterious toxicity against normal cells indicate for the need to selectively protect them. Reactive oxygen and nitrogen species reinforce ionizing radiation cytotoxicity, and compounds able to scavenge these species or enhance antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) should be properly investigated. Antioxidant plant-derived compounds, such as phenols and polyphenols, could represent a valuable alternative to synthetic compounds to be used as radio-protective agents. In fact, their dose-dependent antioxidant/pro-oxidant efficacy could provide a high degree of protection to normal tissues, with little or no protection to tumor cells. The present review provides an update of the current scientific knowledge of polyphenols in pure forms or in plant extracts with good evidence concerning their possible radiomodulating action. Indeed, with few exceptions, to date, the fragmentary data available mostly derive from in vitro studies, which do not find comfort in preclinical and/or clinical studies. On the contrary, when preclinical studies are reported, especially regarding the bioactivity of a plant extract, its chemical composition is not taken into account, avoiding any standardization and compromising data reproducibility.

Genoprotective Effect of Some Flavonoids against Genotoxic Damage Induced by X-rays In Vivo: Relationship between Structure and Activity

“…In these cases, the presence and/or absence of simple hydroxy groups, the esterification of any of them, the planar or non-planar spatial structure in flavonoids, etc., may be determining factors. These elements can radically increase or decrease the activity of these compounds [ 37 , 38 , 39 , 40 , 71 , 83 ], but their assessment in this work was not possible. Administration of procyanidin-rich grape seed extracts (proanthocyanidins) has been reported to reduce radiation-induced oxidative stress in different mouse tissues, which are attributed to a significant increase in SOD, catalase, and GPx activity [ 91 ].…”

“…On the other hand, the mechanisms of action of these compounds are influenced by secondary structural factors, such as the presence or absence of sugars in some of their hydroxy groups (glycosylated forms), the total number of hydroxylated positions, and the existence or not of esterified hydroxyls, mainly with methyl groups. These structural elements of flavonoids are essential for the activation and/or inhibition of multiple enzyme systems involved in the metabolic cascade reactions, such as cyclooxygenases, lipoxygenases, phospholipases, prostaglandinsynthetases [ 4 , 5 , 23 , 37 , 38 , 39 , 40 , 41 , 42 ].…”

“…It seems that the presence of 4–5 free hydroxy groups, the presence of a C2 = C3 double bond conjugated with the C4 carbonyl carbon, and, above all, the fact that one of the hydroxy groups is located on position 3 of the C ring, introduces some level of instability to the product, which confers to it more pro-oxidant than antioxidant genoprotective properties. In any case, rutin itself has difficulty interacting with lipophilic radicals or intervening in the modulation of pro-inflammatory pathways by expressed as reduction in its genoprotective capacity when administered after exposure to ionizing radiation [ 37 , 39 , 90 , 96 , 97 , 98 ].…”

“…[ 4 , 5 , 30 , 31 ]. Some studies have related these effects to the chemical structure of flavonoids, describing that their antioxidant activities, enzyme inhibition or antineoplastic capacities depend on small variations in their basic chemical structure [ 5 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ].…”

Herbal Radioprotectors: A mini-review of the Current Status

“…Certain polyphenols, thiols, fatty acids, vitamins confer protection from carcinogenesis. Polyphenols, garlic extracts were also found effective in case of reducing radiation induced damage to hematopoietic system and central nervous system (Faramarzi et al, 2021). These herbal preparations have been tested for their radioprotective efficacy as whole extracts, isolated constituents, fractionated formulations, polyherbal formulations (Paul et al, 2011) Extracts of various herbs/ plants have been tested for their radioprotective activity viz: Podophyllum hexandrum, Hippophae rhamnoides, Ocimum sanctum, Tinospora cordifolia, Rhodiola imbricate, Emblica officinalis, Centella asiatica, Curcuma longa, Allium sativum, Piper longum, Mentha piperita, Aegle marmelos and Zingiber officinalis on different animal models.…”