Protective effects of cystine and theanine on radiation-induced gastrointestinal syndrome: Modulation of apoptosis, pyroptosis, and crypt survival.

Acute radiation exposure causes severe colonic damage and gastrointestinal (GI) syndrome. Although cystine and theanine (CT) may ameliorate 5 Gy X-ray (0.5531 Gy/min) radiation-induced damage of CT-treated rats (280 mg/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 8-14 Gy 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 10 Gy 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.