Amifostine Suppresses the Side Effects of Radiation on BMSCs by Promoting Cell Proliferation and Reducing ROS Production

Abstract

This study is aimed at investigating the effect of amifostine (AMI) on rat bone marrow stromal stem cells (BMSCs) exposed to 2 Gy radiation. The BMSCs were divided into four groups, namely, group A that received 0 Gy radiation, group B that received 0 Gy radiation and AMI, group C that received 2 Gy radiation, and group D that received 2 Gy radiation and AMI. The proliferation, apoptosis, and distribution of BMSCs in the cell cycle, along with their osteogenesis ability, adipogenesis ability, and ROS production, were subsequently examined. The levels of ALP, PPARγ, P53, and TNFα were determined by Western blotting. The results demonstrated that the proliferation of BMSCs and the levels of ALP in group C were much lower than those in group A. The production of ROS and levels of PPARγ, P53, and TNFα in the group that received 2 Gy radiation were much higher than those in group A. Furthermore, the production of ROS and the levels of PPARγ, P53, and TNFα were much lower in group D than in group C. Additionally, the levels of ALP and extent of cell proliferation were much higher in group D than in group C. The results demonstrated the potential of AMI in reducing the side effects of radiation in BMSCs and in treatment of bone diseases caused by radiation.

RNA Profiling Reveals a Common Mechanism of Histone Gene Downregulation and Complementary Effects for Radioprotectants in Response to Ionizing Radiation

“…Although the mechanisms of amifostine and CBLB502-mediated radioprotection are poorly understood, 39 they are both likely to have a cytoprotective effect and rapid response against IR-induced stress within several hours, 5 , 40 with achieving complex radiation-cytoprotective effects by interfering with genes involved in scavenging free radicals, cell cycle regulation, apoptosis, and inflammation. 6 , 7 , 41 - 46 However, nilestriol requires a longer time, usually hours or days, to exert its protective effects, and its post-irradiation mechanism does not involve primary radiation-induced cellular processes. 3 , 9 These differences in reaction time and mechanism may explain the similarities between amifostine and CBLB502 in terms of the influence on IR-induced RNAs, which was distinct from that of nilestriol.…”

Postradiation Fractures after Combined Modality Treatment in Extremity Soft Tissue Sarcomas

“…Amifostine is a synthetic antioxidant shown to lessen tissue damage by binding free radicals and promoting tissue repair [66]. It has been shown in both animal models to protect bone quality and healing, though most of this work focuses on the mandible rather than long bones [67][68][69]. Additionally, amifostine has been shown to be radioprotective to the physis in combination with misoprostol, selenium, and pentoxifylline [70].…”

Bench to Bedside: Animal Models of Radiation Induced Musculoskeletal Toxicity

“…Amifostine is a radio-protective agent that acts by scavenging free radicals generated by ionizing radiation. A recent in vitro study of rat bone marrow stem cells with or without radiation and amifostine showed that the addition of amisfostine to irradiated cells decreased the amount of reactive oxygen species and DNA damage and increased the levels of cellular proliferation, which is promising [80]. Additionally, Zhang and colleagues showed that in an in vivo rat model, by reducing DNA damage, amifostine may decrease the differentiation of osteoclast precursor cells into differentiated osteoclasts.…”