Antioxidant Supplementation: A Linchpin in Radiation-Induced Enteritis

Mumtaz Anwar, Shabeer Ahmad, Reyhan Akhtar, Akhtar Mahmood, Safrun Mahmood, Mumtaz Anwar, Shabeer Ahmad, Reyhan Akhtar, Akhtar Mahmood, Safrun Mahmood

Abstract

Radiation enteritis is one of the most feared complications of abdominal and pelvic regions. Thus, radiation to abdominal or pelvic malignancies unavoidably injures the intestine. Because of rapid cell turnover, the intestine is highly sensitive to radiation injury, which is the limiting factor in the permissible dosage of irradiation. Bowel injuries such as fistulas, strictures, and chronic malabsorption are potentially life-threatening complications and have an impact on patient quality of life. The incidence of radiation enteritis is increasing because of the current trend of combined chemotherapy and radiation. The consequences of radiation damage to the intestine may result in considerable morbidity and even mortality. The observed effects of ionizing radiation are mediated mainly by oxygen-free radicals that are generated by its action on water and are involved in several steps of signal transduction cascade, leading to apoptosis. The oxyradicals also induce DNA strand breaks and protein oxidation. An important line of defense against free radical damage is the presence of antioxidants. Therefore, administration of antioxidants may ameliorate the radiation-induced damage to the intestine.

Keywords: DNA damage; apoptosis; brush border enzymes; expression; radiation-induced enteritis.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
This is adapted from Nguyen et al and is self-modified. It shows the postulated mechanism of radiation enteritis and other conditions characterized by excessive fibrosis: hyperstimulation of transforming growth factor β1. It also describes the mechanism how hydroxyl radical production and other injuries lead to hyperstimulation of TGF-β1 and finally to clinical manifestations. TGF-β1 indicates transforming growth factor-β1.
Figure 2.
Figure 2.
This is modified by us which shows the model representation of the molecular biology of radiation effect and DNA damage leading to cancer. This also depicts how different exposures to cellular DNA lead to its damage and hence carcinogenesis.
Figure 3.
Figure 3.
Adapted from Campbell and Reece and self-modified. This show different phases of cell cycle, like, G1, M, G2, and S and the check points schematically.
Figure 4.
Figure 4.
Proposed model of radiation-induced enteritis and its protection using antioxidants and can be explained as: when radiation is given to small intestine, then radiation-induced enteritis is observed. After that various manifestations could be observed as DNA damage, physical changes such as body weight, mortality, deregulated levels of brush border enzymes, namely, sucrose, lactase, Alkaline phosphatise (ALP), Gamma-Glutamyl Transpeptidase (γ-GTP), and Leucine aminopeptidase (LAP), and altered expression of marker genes/proteins (ie, of apoptotic machinery genes/proteins) were observed. Upon antioxidant supplementation, the effect of radiation-induced enteritis could be reversed especially with that of vitamin E that proved to be very potent in ameliorating the radiation-induced damage, hence protection.

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Source: PubMed

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