Quercetin 3-O rutinoside prevents gastrointestinal injury through regulation of apoptosis in 7.5 Gy total body irradiated mice

Despite the heightened threat to unforeseen nuclear/radiological exposures worldwide, no countermeasures are currently approved to prevent gastrointestinal (GI) toxicity induced by radiation in humans.In this study, we aim to establish the gastroprotective role of flavonoid, Quercetin-3-O-rutinoside (Q-3-R) against 7.5 Gy total body gamma radiation dose that contributes to the hematopoietic syndrome.Q-3-R (10 mg/kg body weight) was administered intramuscularly to C57BL/6 male mice before exposure to 7.5 Gy and monitored for morbidity and mortality. The GI protection against radiation was ascertained by histopathological and xylose absorption studies. Intestinal apoptosis, crypt proliferation and apoptotic signaling were also investigated in different treatment groups.We found that Q-3-R prevented the radiation-induced loss of mitochondrial membrane potential, maintained ATP levels, regulated the apoptotic pathway, and activated crypt cell proliferation in the intestine. Radiation-induced villi and crypt damage as well as mal-absorption were significantly minimized in the Q-3-R treated group. We observed 100% survival post Q-3-R administration against 33.3% lethality in 7.5 Gy (LD33.3/30) exposed C57BL/6 mice. The Q-3-R pre-treated mice that survived the 7.5 Gy dose revealed no pathological changes related to the development of fibrosis in the intestine and thickened mucosal wall till 4 months post irradiation. Complete hematopoietic recovery was observed in these surviving mice when compared to age matched control.The findings revealed that Q-3-R regulated the apoptotic process to achieve GI protection against LD33.3/30 dose (7.5 Gy) that primarily caused death due to hematopoietic failure. The recovery observed in mice survivors suggested that this molecule may also have the potential to minimize side effects on normal tissues during radiotherapy.