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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Amifostine is an organic thiophosphate prodrug that is hydrolyzed in vivo by alkaline phosphatase to an active cytoprotective thiol metabolite (WR-1065). The selective protection of healthy tissue is thought to be due to higher alkaline phosphatase activity, pH, and vascular permeation of healthy compared to malignant tissues. Once inside cells, amifostine acts as a thiol-based free radical scavenger capable of limiting free radical damage caused by exposure to radiation and some cytotoxic chemotherapy agents. It has also been suggested to induce cellular hypoxia, accelerate DNA repair, inhibit apoptosis, and alter gene expression. It has also been used to reduce the incidence of neutropenia-related infection and fever caused by DNA-interactive agents such as cross-linking (e.g., cyclophosphamide) and platinum-containing agents (e.g., cisplatin). Administered intravenously, it is recommended that patients are well-hydrated prior to receiving amifostine. Side effects include GI disturbances (e.g., diarrhea, nausea, vomiting), hypocalcemia, hypotension (occurring in 62% of patients), skin disorders (e.g., erythema multiforme, erythroderma, Stevens–Johnson syndrome, and toxic epidermal necrolysis), and immune hypersensitivity syndrome.
Toward Clinical Pharmacologic Otoprotection
Published in Stavros Hatzopoulos, Andrea Ciorba, Mark Krumm, Advances in Audiology and Hearing Science, 2020
Colleen G. Le Prell, Kelly Roth, Kathleen C. M. Campbell
Amifostine is typically delivered by intravenous injection by a health care professional 15–30 min before cisplatin infusion to decrease the risk of kidney problems and prevent dry mouth side effects. There are a number of contraindications for use, including potential drug interactions, which will be reviewed prior to the prescription of this drug.
Perioperative and anaesthetic care
Published in Tom Cecil, John Bunni, Akash Mehta, A Practical Guide to Peritoneal Malignancy, 2019
Nina Ashraf-Kashani, John Bell
Intra-operative euvolaemia is a specific intra-operative target. Low cardiac output and poor kidney perfusion increase the risk of AKI and should be avoided [28]. Goal-directed fluid therapy using cardiac output monitoring to target administration of fluid to specific circulatory parameters is associated with improved outcomes in CRS with HIPEC [14]. Amifostine is a cytoprotective agent that has been used in the prevention of toxicity caused by platinum-based chemotherapy agents [29]. It is an organic thiophosphate involved in free radical scavenging and promotion of DNA repair mechanisms [30]. There is some evidence to suggest a potential reduction in AKI following cisplatin HIPEC [31]; however, its administration is associated with a risk of profound hypotension. In the setting of major fluid shifts, the potential for haemorrhage and a systemic inflammatory response may not be tolerated by some patients. It is not used routinely in PMI Basingstoke. Administration of a single specific agent is unlikely to result in significant reductions in renal deterioration postoperatively without additional preventative and supportive measures. These form the mainstay of the approach to the prevention of renal injury during the perioperative period.
Radioprotective effect of mistletoe extract on intestinal toxicity: in vivo study using adult zebrafish
Published in International Journal of Radiation Biology, 2023
Sunmin Park, Suhyun Kim, Soonil Koun, Hae-Chul Park, Won Sup Yoon, Chai Hong Rim
The therapeutic efficacy of cancer radiotherapy is based on the difference in the sensitivity of cancer and normal cells to radiation. Theoretically, modifiers capable of lowering radiotoxicity in normal organs have the potential to interfere with cancer cell death. Thus, it is essential to discover substances that act selectively on cancer cells. Currently, the only clinical radioprotector approved by the FDA is amifostine (Brizel et al. 2000). However, radioprotectors are still not commonly used in clinical practice because of concerns regarding the possibility of lowering the efficacy of cancer treatment (Hall and Giaccia 2006). Furthermore, amifostine can cause side effects, such as hypertension, somnolence, and fatigue. The rate of discontinuation due to side effects has been reported to be as high as 20% (Koukourakis and Maltezos 2006). However, mistletoe extract has been shown to improve the quality of life of patients receiving chemotherapy (Kienle and Kiene 2007). Recent studies have shown that mistletoe extract can relieve cancer symptoms, including fatigue, pain, and anorexia, without notable toxicity (Pelzer et al. 2018, 2022). In addition, as it has shown antitumor effects in preclinical studies and some observational clinical studies, it has sufficient potential as a clinically useful radioprotective agent (Kienle and Kiene 2007; Bonamin et al. 2017).
Protective mechanism of a novel aminothiol compound on radiation-induced intestinal injury
Published in International Journal of Radiation Biology, 2023
Xinxin Wang, Renbin Yuan, Longfei Miao, Xuejiao Li, Yuying Guo, Hongqi Tian
Although several research groups have found a variety of radiation protective agents, they are still in the early stages of development (Fischer et al. 2018). Amifostine is the first radiation protective agent approved by FDA for reducing the incidence of moderate to severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer (Gula et al. 2013). However, its disadvantages, such as high toxicity and its short half-life, limit its clinical application (Korst et al. 1997). Our research group recently designed and synthesized a radiation protective agent known as compound 8, which is effective at protecting from radiation damages. In this study, the efficacies of the new amino-mercaptan compounds were evaluated, and the related mechanisms were studied. The results showed that the new small molecule amino-mercaptan compounds have a low initial dose and high safety.
Metabolomics-based predictive biomarkers of radiation injury and countermeasure efficacy: current status and future perspectives
Published in Expert Review of Molecular Diagnostics, 2021
Vijay K Singh, Thomas M Seed, Amrita K Cheema
Amifostine (WR2721, Ethyol) is a radioprotector which has been shown to reduce acute radiation injury mainly through free radical scavenging, although other cytoprotective mechanisms been reported [98]. It also provides protection against late-arising, radiation-induced malignancies by dampening radiation-induced mutagenesis [99–102]. Amifostine is an FDA-approved agent for limited indications: (i) to reduce the renal toxicity as a result of repeated use of cisplatin in ovarian cancer patients, and (ii) to reduce the xerostomia in head and neck cancer patients receiving radiotherapy [103–107]. Due to adverse side effect issues, amifostine failed to get US FDA approval as a radioprotector for ARS [98]. Nevertheless, it has been shown experimentally that by using its low doses prophylactically, its toxic side effects can be minimized and radioprotective efficacy can be retained [102,108,109].