The effects of resveratrol and selected metabolites on the radiation and antioxidant response

Abstract

Excess reactive oxygen species (ROS) generated from ionizing radiation (IR) or endogenous sources like cellular respiration and inflammation produce cytotoxic effects that can lead to carcinogenesis. Resveratrol (RSV), a polyphenol with antioxidant and anticarcinogenic capabilities, has shown promise as a potential radiation modifier. The present study focuses on examining the effects of RSV or RSV metabolites as a radiation modifier in normal tissue. RSV or a RSV metabolite, piceatannol (PIC) did not protect human lung fibroblasts (1522) from the radiation-induced cell killing. Likewise, neither RSV nor PIC afforded protection against lethal total body IR in C3H mice. Additional research has shown protection in cells against hydrogen peroxide when treated with RSV. Therefore, clonogenic survival was measured in 1522 cells with RSV and RSV metabolites. Only the RSV derivative, piceatannol (PIC), showed protection against hydrogen peroxide mediated cytotoxicity; whereas, RSV enhanced hydrogen peroxide sensitivity at a 50 µM concentration; the remaining metabolites evaluated had little to no effect on survival. PIC also showed enhancement to peroxide exposure at a higher concentration (150 µM). A potential mechanism for RSV-induced sensitivity to peroxides could be its ability to block 1522 cells in the S-phase, which is most sensitive to hydrogen peroxide treatment. In addition, both RSV and PIC can be oxidized to phenoxyl radicals and quinones, which may exert cytotoxic effects. These cytotoxic effects were abolished when HBED, a metal chelator, was added. Taken together RSV and many of its metabolic derivatives are not effective as chemical radioprotectors and should not be considered for clinical use.

The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation

“…Resveratrol has been used in traditional Japanese and Chinese medicine to treat fungal diseases, various skin inflammations, and cardiovascular and liver diseases [9], [10]. Resveratrol has recently been shown to have various therapeutic purposes, including antioxidation, anti-proliferation, and chemopreventive effects [11], [12]. Additionally, accumulating evidence indicates that resveratrol possesses an antitumor effect by inhibiting tumor cell growth and inducing apoptosis [13]–[16].…”

The effect ofin vivoresveratrol supplementation in irradiated mice on the induction of micronuclei in peripheral blood and bone marrow reticulocytes

“…Then RSV is not protector against cell killing in vitro or lethality in vivo (54). However, results of other studies may indicate that it would protect against lethality, but the doses of irradiation used were much lower (55,56).…”

“…The possible mechanism, by which RSV protect DNA against induction by IR of chromosomal aberration in bone marrow cells could be that RSV interact with IR-induced secondary radicals or ROS (54). Depending on the individual-based human DNA status, RSV was able to switch from antioxidant to pro-oxidant (60) and may act as an efficient and radical scavenger (61).…”

“…IR deposits energy into biological material resulting in the very quick generation of highly reactive free radicals (58). In order to act forcefully, chemical radioprotector should be present during IR exposure to scavenge radiation-induced primary radicals, which have short lifetime (54). On the other hand, radioprotector should also be present later than longer lived secondary radicals and ROS are formed (59).…”

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“…Though several authors have reported on the radioprotective potential of RSV, Fabre et al, have, however, reported that RSV does not show any radio-protective effect 98 . We, therefore, carried some studies to check the radio-protective effect of RSV from ionizing radiations.…”