Protective effect of genistein on radiation-induced intestinal injury in tumor bearing mice

Abstract

BackgroundRadiation therapy is the most widely used treatment for cancer, but it causes the side effect of mucositis due to intestinal damage. We examined the protective effect of genistein in tumor-bearing mice after abdominal irradiation by evaluation of apoptosis and intestinal morphological changes.MethodsMouse colon cancer CT26 cells were subcutaneously injected at the flank of BALB/c mice to generate tumors. The tumor-bearing mice were treated with abdominal radiation at 5 and 10 Gy, and with genistein at 200 mg/kg body weight per day for 1 d before radiation. The changes in intestinal histology were evaluated 12 h and 3.5 d after irradiation. To assess the effect of the combination treatment on the cancer growth, the tumor volume was determined at sacrifice before tumor overgrowth occurred.ResultsGenistein significantly decreased the number of apoptotic nuclei compared with that in the irradiation group 12 h after 5 Gy irradiation. Evaluation of histological changes showed that genistein ameliorated intestinal morphological changes such as decreased crypt survival, villus shortening, and increased length of the basal lamina 3.5 d after 10 Gy irradiation. Moreover, the genistein-treated group exhibited more Ki-67-positive proliferating cells in the jejunum than the irradiated control group, and crypt depths were greater in the genistein-treated group than in the irradiated control group. The mean weight of the CT26 tumors was reduced in the group treated with genistein and radiation compared with the control group.ConclusionGenistein had a protective effect on intestinal damage induced by irradiation and delayed tumor growth. These results suggest that genistein is a useful candidate for preventing radiotherapy-induced intestinal damage in cancer patients.

Gamma-aminobutyric acid ameliorates gamma rays-induced oxidative stress in the small intestine of rats

“…Kim et al (2012) indicated that they are very sensitive biodosimetric markers after irradiation process. Acute effects of irradiation on the intestinal mucosa may be attributed to inhibition of mitotic divisions in the Lieberkühn crypts, and the loss of proliferative functions results in drop in the development of the small intestine epithelium and reduces the small intestine permeability to gut bacteria and antigens, which may intensify mucosal inflammation and dysfunction or lead to bacteremia (Son et al, 2013). The current study showed that 6 Gy whole body gamma irradiation of male albino rats triggered oxidative stress indicated by a highly significant increase in the oxidant biomarkers (AOPP and MDA) and a highly significant decrease in antioxidant enzyme activity (CAT and GSH-Px).…”

Radioprotective effects of genistein on HL-7702 cells via the inhibition of apoptosis and DNA damage

“…Different concentrations of GEN (1, 5, 10, 20 μM) were applied in the GEN treatment group 24 h prior to X ray irradiation, and were also present in the medium after irradiation. Cells were irradiated with different doses of X rays (6,8,12,16,20 Gy) (Varian 2100, C/D linear accelerator) at a dose rate of 300 cGy/min, and were harvested 24, 48 and 72 h after irradiation.…”

“…Other data demonstrated that GEN also had radioprotective effects in nonhematopoietic tissues, including the lung, testis and intestine [17][18][19]. Son et al [20] found that GEN had a protective effect on intestinal damage induced by irradiation and inhibited tumor growth. Our previous studies indicated that soybean isoflavone treatment could significantly alleviate the liver oxidative stress and damage induced by 60 Co-gamma irradiation [21].…”

Plant Extracts and Plant-Derived Compounds: Promising Players in Countermeasure Strategy Against Radiological Exposure: A Review

“…Further, quantitative real-time polymerase chain reaction (qRT-PCR) microarrays examination of cell cycle specific genes in bone marrow cells have shown that GN-treated mice expressed fewer DNA damage responsive and cell cycle checkpoint genes than untreated controls, thereby providing protection from acute myelotoxicity (Davis et al, 2008). The radioprotective ability of GN was further supported by some of the recent works showing prevention of irradiation-induced damage to hematopoietic system and intestinal damages Son et al, 2013), and rendering delay in tumour growth (Son et al, 2013).…”