Protective Effects of Cystine and Theanine on Radiation-Induced Gastrointestinal Syndrome: Modulation of Apoptosis, Pyroptosis, and Crypt Survival.

Abstract

Acute radiation exposure causes severe colonic damage and gastrointestinal (GI) syndrome. Although cystine and theanine (CT) may ameliorate 5Gy X-ray (0.5531Gy/min) radiation-induced damage of CT-treated rats (280mg/kg for 5 days), their precise mechanisms in protecting colonic crypt cells and maintaining epithelial integrity remain unclear. Using a rat model of radiation-induced GI injury following 8 to 14Gy exposure, we explored CT treatment effects on crypt survival, apoptosis, DNA damage, and inflammation. CT treatment eliminated bloody diarrhea (p=0.0075) and decreased ulceration to 6.5% compared to 35.1% in controls (p<0.01). Living crypt increased to 86.7% from 37.7% in controls (p<0.01) at 10Gy exposure. CT enhanced genomic stability by reducing γ-H2AX foci formations and pyroptotic cell death mediated by AIM2 inflammasome activation, including stem cells. CT treatment enhances crypt survival and limits apoptosis/pyroptosis in radiation-induced GI syndrome, indicating radioprotective potential.