Epigallocatechin-3-Gallate Protects Pro-Acinar Epithelia Against Salivary Gland Radiation Injury

Abstract

Antioxidant agents are promising pharmaceuticals to prevent salivary gland (SG) epithelial injury from radiotherapy and their associated irreversible dry mouth symptoms. Epigallocatechin-3-gallate (EGCG) is a well-known antioxidant that can exert growth or inhibitory biological effects in normal or pathological tissues leading to disease prevention. The effects of EGCG in the various SG epithelial compartments are poorly understood during homeostasis and upon radiation (IR) injury. This study aims to: (1) determine whether EGCG can support epithelial proliferation during homeostasis; and (2) investigate what epithelial cells are protected by EGCG from IR injury. Ex vivo mouse SG were treated with EGCG from 7.5–30 µg/mL for up to 72 h. Next, SG epithelial branching morphogenesis was evaluated by bright-field microscopy, immunofluorescence, and gene expression arrays. To establish IR injury models, linear accelerator (LINAC) technologies were utilized, and radiation doses optimized. EGCG epithelial effects in these injury models were assessed using light, confocal and electron microscopy, the Griess assay, immunohistochemistry, and gene arrays. SG pretreated with EGCG 7.5 µg/mL promoted epithelial proliferation and the development of pro-acinar buds and ducts in regular homeostasis. Furthermore, EGCG increased the populations of epithelial progenitors in buds and ducts and pro-acinar cells, most probably due to its observed antioxidant activity after IR injury, which prevented epithelial apoptosis. Future studies will assess the potential for nanocarriers to increase the oral bioavailability of EGCG.

Mechanism, Prevention, and Treatment of Radiation-Induced Salivary Gland Injury Related to Oxidative Stress

“…SG pretreated with 7.5 µg/mL of EGCG promoted epithelial proliferation and the development of pro-acinar buds and ducts in regular homeostasis. In addition, EGCG’s antioxidant activity after IR injury effectively prevents epithelial cell apoptosis [ 107 ]. As a strong antioxidant, α-lipoic acid (ALA) is highly reactive to free radicals that can prevent normal tissue damage and dysfunction caused by radiation by increasing the level of glutathione in the tissues; this has been confirmed in the small intestine and thyroid of rats [ 108 , 109 ].…”

(-)-Epigallocatechin-3-Gallate (EGCG) Modulates the Composition of the Gut Microbiota to Protect Against Radiation-Induced Intestinal Injury in Mice

“…Regular consumption of green tea may prevent cancer, diabetes, atherosclerosis, obesity, as well as bacterial and viral infections. Both in vitro and in vivo studies showed that green tea reduces the radiation-induced damage to cells and tissues ( 14 , 29 ). The present study revealed that the administration of EGCG prior to TBI preserved the crypt-villus architecture of the murine small intestine by promoting the survival of the Lgr5 + ISCs and the regeneration of the intestinal epithelium.…”

Plant Polyphenols for Aging Health: Implication from Their Autophagy Modulating Properties in Age-Associated Diseases

“…Epigallocatechin gallate (EGCG) is the most abundant green tea polyphenol with numerous health benefits [ 79 , 80 , 81 , 82 ]. In colorectal carcinoma cells (HT-29), EGCG induced autophagy to inhibit the proliferation of cells through the regulation of the glycerophospholipid metabolic pathway [ 83 ].…”