• Biomedical Science Letters
• /
• v.29 no.4
• /
• pp.287-295
• /
• 2023

Amifostine was developed to protect cells, but it is known to induce cytotoxicity and apoptosis, and the exact mechanism is unknown. In this study, we investigated how the DNA mismatch repair (MMR) system interacts with p53 to prevent apoptosis, cell cycle arrest, and cytoprotective effects induced by amifostine. HCT116 colon cancer cells sublines HCT116/p53+,HCT116/p53+, HCT116/p53-, HCT116/E6 and HCT116+ch3/E6 cells were used for evaluation. Amifostine induced G1 arrest and increased toxicity two-fold in p53- cells regardless of MMR expression. Both G1 cell cycle arrest and induction of p53 protein peaked at 24 h after the start of amifostine exposure. Both G1 cell cycle arrest and induction of p53 protein peaked at 24 h after the start of amifostine exposure. Amifostine induced the expression of p21 protein in both p53+ and p53- cells. As for apoptosis, compared to p53- cells, p53+ cells showed 3.5~4.2 times resistance to amifostine-induced apoptosis. HCT116+E6 with both p53 and MMR loss showed maximum apoptosis at 48 h, and HCT116+ch3/E6HCT116+ch3/E6 with p53 loss showed maximum apoptosis at 24 h. As a result, it was confirmed through in vitro experiments that amifostine-induced G1 cell cycle arrest and apoptosis are mediated through a pathway dependent on MMR and p53 protein.

• Journal of Chest Surgery
• /
• v.31 no.9
• /
• pp.845-854
• /
• 1998

Background: S-2-(3 aminoprophlamino) ethylphosphorothioic acid(WR-2721) is one of the radical scavenging thiols. We tested its protective effects in the reperfused heart. Material and Method: The experimental setup was the constant pressure Langendorffs perfusion system. We investigated the radical scavenging properties of this compound in isolated rat hearts which were exposed to 20 minutes ischemia and 20 minutes reperfusion. Four experimental groups were used:group I, control, Amifostine 50 mg(1 mL) peritoneal injection 30 minutes before ischemia(group II), Amifostine 10 mg(0.2 mL) injection during ischemia through coronary artery(group III),and Amifostine 50 mg(1 mL) peritoneal injection 2 hrs before ischemia(group IV). The experimental parameters were the levels of latate, CK-MB, and adenosine deaminase(ADA) in frozen myocardium, the quantity of coronary flow,and left ventricular developed pressure, and it's dp/dt. Statistical analysis was performed using repeated measured analysis of variance and student t-test. Result: The coronary flow of group II and IV were less than group I and III at equilibrium state but recovery of coronary flow at reperfusion state of group II, III, and IV were more increased compared with group I. The change of systolic left ventricular devoloping pressure of group II and IV were less than control group at equilibrium state, which seemed to be the influence of the pharmacological hypotensive effect of amifostine. But it was higher compared with group I at reperfusion state. The lactic acid contents of group II were less than control group in frozen myocardium.(Group I was 0.20 0.29 mM/g vs Group II, which was 0.10 0.11 mM/g). The quantity of CK-MB in myocardial tissue was highest in group IV (P=0.026 I: 120.0 97.8 U/L vs IV: 242.2 79.15 U/L). The adenosine deaminase contents in the coronary flow and frozen myocardium were not significantly different among each group. Conclusion: Amifostine seemed to have significant cardioprotective effect during ischemia and reperfusion injuries of myocardium.

• Journal of Veterinary Science
• /
• v.24 no.3
• /
• pp.35.1-35.10
• /
• 2023

Background: Titanium is the most widely used metal for bone integration, especially for cancer patients receiving ionizing radiation. This study aimed to investigate the amifostine administration that would reduce the effects of radiation on bone healing and osseointegration in rat models. Objectives: It is aimed that the application of amifostine in rats receiving radiotherapy treatment will reduce the negative effects of ionizing radiation on the bone. Methods: Thirty-five adult male Wistar rats were randomly divided into one healthy and four experimental groups. In three consecutive days, two experimental groups of rats (AMF-RT-IMP and RT-IMP) were exposed to radiation (15 Gy/3 fractions of 5 Gy each). Then the titanium implants were inserted into the left tibia. Before the radiotherapy process, a 200 mg/kg dose of amifostine (AMF) was administered to the rats in the AMF-IMP and AMF-RT-IMP groups. Twenty-eight days after the screw implant, all rats were sacrificed, and their blood samples and tibia bones were collected for analysis. Results: The results indicated an accelerated bone formation and a more rapid healing process in the screw implants in the AMF-IMP, AMF-RT-IMP, and AMF-RT groups than in the RT-IMP group. Also, bone-implant contact area measurement and inflammation decreased with amifostine treatment in the implants subjected to irradiation (p < 0.05). Conclusions: The results obtained in the present study suggested that amifostine prevents the losses of bone minerals, bone integrity, and implant position from ionizing-radiation when given before exposure.

• Advances in Traditional Medicine
• /
• v.10 no.1
• /
• pp.1-6
• /
• 2010

The efficacy of the radioprotective effect of Callophyllis japonica ethyl acetate (CJEA) extract was studied by comparing it to that of amifostine, a well-known radioprotective agent, and by evaluating the dose reduction factor, an indicator of radioprotective efficacy. Pretreatment with CJEA extract (100 mg/kg body weight) prior to receiving 12 Gy irradiation significantly improved the survival of jejunal crypts at 3.5 day post-irradiation, but attenuated the level of malondialdehyde compared to vehicle alone (P < 0.01). A similar gastroprotective effect was also obtained in the amifostine-treated irradiated group (P < 0.01). The efficacy of the radioprotective effect was further confirmed by the dose reduction factor, 1.41. Collectively, these results suggest that CJEA extract is a useful radioprotectant whose efficacy is similar to that of amifostine and whose radioprotective mechanism is in part the reduction of lipid peroxidation caused by gamma irradiation.

• Proceedings of the Korean Society of Developmental Biology Conference
• /
• 2002.02a
• /
• pp.48-48
• /
• 2002

• Journal of Radiation Protection and Research
• /
• v.41 no.3
• /
• pp.253-259
• /
• 2016

Background: This study investigated the effects of zoledronic acid (ZA) on radiation-induced bone loss in C3H/HeN mice. Materials and Methods: C3H/HeN mice were divided into sham control and three irradiated groups (3 Gy, gamma ray). The irradiated mice were treated for 12 weeks with vehicle, amifostine (intraperitoneal injection), or ZA (subcutaneous injection). Grip strength, uterus weight, and serum alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) levels were measured. Tibiae were analyzed using micro-computed tomography. Results and Discussion: Treatment of ZA ($100{\mu}g{\cdot}kg^{-1}{\cdot}week^{-1}$) significantly preserved trabecular bone volume, trabecular thickness, trabecular number, trabecular separation, bone mineral density of proximal tibia metaphysic, and cortical bone volume, but did not alter the uterus weight of the mice. The administration of ZA for 12 weeks lowered serum ALP and TRAP levels in irradiated mice, suggesting that ZA can reduce the bone turnover rate in mice. No differences were apparent between the amifostine-treated group and the irradiation control group. Conclusion: The results indicate that ZA can prevent radiation-induced bone loss in mice.

• Proceedings of the Korean Nuclear Society Conference
• /
• 2004.10a
• /
• pp.1204-1205
• /
• 2004

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.10
• /
• pp.5631-5635
• /
• 2013

Cochlea hair cell death is regarded to be responsible for the radiation-induced sensorineural hearing loss (SNHL), which is one of the principal complications of radiotherapy (RT) for head and neck cancers. In this mini-review, we focus on the current progresses trying to unravel mechanisms of radiation-induced hair cell death and find out possible protection. P53, reactive oxygen species (ROS) and c-Jun N-terminal kinase (JNK) pathways have been proposed as pivotal in the processes leading to radiation hair cell death. Potential protectants, such as amifostine, N-acetylcysteine (NAC) and epicatechin (EC), are claimed to be effective at reducing radiation-inducedhair cell death. The RT dosage, selection and application of concurrent chemotherapy should be pre-examined in order to minimize the damage to cochlea hair cells.

• Radiation Oncology Journal
• /
• v.36 no.4
• /
• pp.265-275
• /
• 2018

Cancer is a complex multifaceted illness that affects different patients in discrete ways. For a number of cancers the use of chemotherapy has become standard practice. Chemotherapy is a use of cytostatic drugs to cure cancer. Cytostatic agents not only affect cancer cells but also affect the growth of normal cells; leading to side effects. Because of this, radiotherapy gained importance in treating cancer. Slaughtering of cancerous cells by radiotherapy depends on the radiosensitivity of the tumor cells. Efforts to improve the therapeutic ratio have resulted in the development of compounds that increase the radiosensitivity of tumor cells or protect the normal cells from the effects of radiation. Amifostine is the only chemical radioprotector approved by the US Food and Drug Administration (FDA), but due to its side effect and toxicity, use of this compound was also failed. Hence the use of herbal radioprotectors bearing pharmacological properties is concentrated due to their low toxicity and efficacy. Notably, in silico methods can expedite drug discovery process, to lessen the compounds with unfavorable pharmacological properties at an early stage of drug development. Hence a detailed perspective of these properties, in accordance with their prediction and measurement, are pivotal for a successful identification of radioprotectors by drug discovery process.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.1
• /
• pp.291-297
• /
• 2014

The radioprotective effects of a single administration of kojic acid (KA) against ionizing radiation were evaluated via assessment of 30-day survival and alterations of peripheral blood parameters of adult C57BL/6 male mice. The 30-day survival rate of mice pretreated with KA (75 or 300 mg/kg body weight, KA75 or KA300) subcutaneously 27 h prior to a lethal dose (8 Gy, 153.52 cGy/min) of gamma irradiation was higher than that of mice irradiated alone (40% or 60% vs 0%). It was observed that the white blood cell (WBC) count/the red blood cell (RBC) count, haemoglobin content, haematocrit and platelet count of mice with or without KA pretreatment as exposed to a sub-lethal dose (4 Gy, 148.14 cGy/min) of gamma irradiation decreased maximally at day 4/day 8 post-irradiation. Although the initial WBC values were low in KA300 or WR-2721 (amifostine) groups, they significantly recovered to normal at day 19, whereas in the control group they did not. The results from the cytotoxicity and cell viability assays demonstrated that KA could highly protect Chinese hamster ovary (CHO) cells against ionizing radiation with low toxicity. In summary, KA provides marked radioprotective effects both in vivo and in vitro.