amifostine / Generic mfg. - LARVOL DELTA

Ursolic acid derivative UA312 ameliorates ionizing radiation-induced cardiotoxicity and neurodevelopmental toxicity in zebrafish via targeting chrna3 and grik5. (PubMed, Acta Pharmacol Sin) - "Currently, amifostine is the only radiation-protective agent used for clinical indications related to radiation therapy, but this compound has multiple drawbacks including high toxicity, short half-life and no protective effect on the nervous system...In conclusion, this study identified a promising radioprotective drug, UA312, which alleviates IR-induced cardiotoxicity and neurodevelopmental toxicity in zebrafish by targeting chrna3 and grik5. UA312 may be developed as a novel radioprotective agent against acute IR damage in humans."

Journal • Cardiovascular

Protective Effect of Amifostine on Radiotherapy-Applied Cardiovascular Tissue. (PubMed, Anatol J Cardiol) - "AMI has a radioprotective and antioxidant effect against RT-induced cardiovascular toxicity."

Journal • Cardiovascular • Inflammation • CD68

Preventing Hearing Loss in Children Receiving Cisplatin: A Systematic Review and Meta-Analysis. (PubMed, Laryngoscope) - "These results show mild success in reducing the incidence of hearing loss in children undergoing chemotherapy with cisplatin. However, the literature is limited, and further investigation is warranted."

Journal • Retrospective data • Review • Otorhinolaryngology

Probing the Multitargeted Potency of FDA-approved Amifostine against MRSA and Control Comparison with Sulfamethoxazole to Establish Alternative Medications. (PubMed, Microb Pathog) - "We also performed Interaction Fingerprints, pharmacokinetics, 5ns WaterMap and 100ns MD Simulation in water. We compared the results and extended the study with binding free energy and total energy of each MD simulation trajectory computations and found that Amifostine is a far better drug than Sulfamethoxazole-however, experimental validation is needed before its human use."

FDA event • Journal • Infectious Disease • Oncology • Ovarian Cancer • Septic Shock • Solid Tumor

Screening model in Caenorhabditis elegans for radioprotective natural products. (PubMed, Int J Radiat Biol) - "Known radioprotective agents, including Amifostine (WR2721), Lycium barbarum extract (LBE), and Trillium tschonoskii fraction (TTF), served as positive controls to validate the reliability of the model...Our results of the model application revealed that teas with lower fermentation levels, such as green tea and oolong tea, particularly the n-butanol and ethyl acetate fractions from oolong tea, exhibited significant radioprotective activity. This study presents an effective in vivo approach for the initial screening of radioprotective natural products."

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Effects of Whole-Body Carbon-Ion Beam Irradiation on Bone Marrow Death in Mice and an Examination of Candidates for Protectors or Mitigators against Carbon-Ion-Beam-Induced Bone Marrow Death. (PubMed, Radiat Res) - "Based on the radio-protective effects of amifostine and cysteamine, the contribution of ROS/free radicals to carbon-ion-beam-induced bone marrow death was 70-90% to that of photon irradiation. Since the suppression of tumor growth by carbon-ion-beam irradiation was not inhibited by the treatment with γTDMG or Zn-yeast, both mitigators have potential as normal tissue-selective protectors in carbon-ion irradiation."

Journal • Preclinical • Oncology

Effect of amifostine on apoptotic inflammatory makers in cisplatin induced brain damage in rats. (PubMed, J Complement Integr Med) - "These outcomes demonstrated amifostine's ability to lessen the histological changes brought on by cisplatin. To sum up, SiNPs@AMF may be a suitable and secure supplemental treatment agent to lessen cisplatin's toxicity in the brain and enhance the treatment's effects throughout chemotherapy."

Journal • Preclinical • CNS Disorders • Vascular Neurology • CASP3 • CCL2 • GFAP

Is Punica granatum Efficient Against Sepsis? A Comparative Study of Amifostine Versus Pomegranate. (PubMed, Life (Basel)) - "Histopathological evaluation revealed reduced MMP-2 and MMP-9 immunopositivity in the PGPE250 and PGPE500 groups. These findings highlight the lung-protective properties of PGPE, underscoring its potential as a therapeutic agent for sepsis-induced acute lung injury."

Journal • Acute Lung Injury • Infectious Disease • Oncology • Respiratory Diseases • Septic Shock • MMP2 • MMP9 • TNFA

Systematic Reviews on the Management of Xerostomia and Hyposalivation-An Umbrella Review. (PubMed, Gerodontology) - "Salivary substitutes and stimulants mostly acted as moisturisers and some as saliva stimulants, with short-term effect. More than 80% of the reviews were appraised as 'critically low' quality. Well-designed and well-reported systematic reviews are still needed to increase the level of evidence on dry mouth management methods."

Journal • Review • Dental Disorders • Xerostomia

Managing strategies of chemotherapy and radiotherapy-induced oral mucositis. (PubMed, Cancer Treat Rev) - "For example, clinical trials assessing established drugs such as melatonin, clonidine, and pentoxifylline indicate promising potential for managing OM. Besides, Verbascoside, Palifermin, Amifostine, and Avasopasem manganese can be suggested for OM management, while the side effects should be monitored. The accessibility and cost/effectiveness of specific managing strategies of OM should be considered when selecting appropriate options."

Clinical • Journal • Review • Head and Neck Cancer • Mucositis • Oncology • Solid Tumor • Stomatitis

A systematic review of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies: prevention strategies. (PubMed, Support Care Cancer) - "This systematic review continues to support the potential of tissue-sparing tecniques and intensity-modulated radiation therapy (IMRT) to preserve salivary gland function in patients with head and neck cancer, with limited evidence on other preventive strategies, including acupuncture and bethanecol. Preventive focus should be on optimized and new approaches developed to further reduce radiation dose to the parotid, the submandibular, and minor salivary glands. As these glands are major contributors to moistening of the oral cavity, limiting the radiation dose to the salivary glands through various modalities has demonstrated reduction in prevalence and severity of salivary gland hypofunction and xerostomia. There remains no evidence on preventive approaches for checkpoint inhibitors and other biologicals due to the lack of RCTs."

Journal • Review • Dental Disorders • Head and Neck Cancer • Oncology • Solid Tumor • Xerostomia

Unmet Needs in Multiple Myeloma and Potential Solutions: A Systemic Literature Review (ASH 2024) - "Other unmet needs reported were patient and family experience/supportive care (11%), pathophysiology (4%), diagnosis/response assessment (4%), toxicity management/prevention (3%) and poor prognosis (4%).Unmet needs that were reported starting from 2010 [and their proposed solutions] include treatment of high-risk cytogenetic features (4%) [elotuzumab/isatuximab/melflufen/selinexor/anti-BCMA conjugates], treatment of plasma cell leukemia/extramedullary disease (3%) [utilizing MM drugs (daratumumab/boretezemib/melfufen/frontline ASCT etc.)], prevention/management of toxicities (mucositis, neuropathy, nephropathy and GVHD) (1%) [CR4056/amifostine/cannabidiol], treatment/prevention of thromboembolism (1%) [risk assessment model for thromboembolism/studies on anticoagulation], treatment of frail/elderly (1%) [SEA BCMA/melflufen], immune response in MM (<1%) [immunological studies], and measures to assess response to treatment (<1%) [heavy light chain ratio/DW..."

Review • Cardiovascular • Geriatric Disorders • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Mucositis • Multiple Myeloma • Novel Coronavirus Disease • Oncology • Orthopedics • Pain • Renal Disease • Respiratory Diseases

Self-Assembled EGCG Nanoparticles with Enhanced Intracellular ROS Scavenging for Skin Radioprotection. (PubMed, Int J Nanomedicine) - "The only clinically approved radioprotective agent, amifostine, is associated with numerous side effects, underscoring the urgent need for the development of safe and effective radioprotective agents...In animal levels, EGCG NPs exhibited markedly improved radioprotective efficacy over free EGCG, effectively reducing skin edema and ulceration, alleviating pathological conditions such as interstitial edema, dermal fluid accumulation, and inflammatory infiltration, decreasing the duration of skin injury, and promoting wound healing. This work offers novel insights into the therapeutic application of EGCG NPs as a potential alternative for skin radioprotection and provides a powerful approach for developing radioprotective agents derived from natural products."

Journal

Preventive effects of melatonin and amifostine on irradiated rats with experimental periodontitis. (PubMed, BMC Oral Health) - "Both melatonin and amifostine can significantly limit RT-induced periodontal bone loss by suppressing inflammatory stress, apoptotic mechanisms, and RANKL-related osteoclastic activity. Given the limited side effects of melatonin, it may be an alternative to amifostine."

Journal • Preclinical • Dental Disorders • Osteoporosis • Periodontitis • CASP3 • IL10 • IL1B • IL6 • TNFA

Integrating Radioprotective Agents into Post-Mastectomy Radiotherapy: Optimization of Reconstructive Outcomes in Breast Cancer. (PubMed, J Surg Res (Houst)) - "The role of several radioprotective agents, including amifostine, N-acetylcysteine, tempol, manganese superoxide dismutase (MnSOD) plasmid liposomes, vitamin E, and beta-carotene has been analyzed with a focus on their logistical applications in breast reconstruction. Despite several challenges, the integration of radioprotective agents into post-mastectomy radiotherapy protocols offers significant potential to improve reconstructive outcomes. Development of novel radioprotective agents with improved selectivity and fewer side effects and large-scale clinical trials in diverse group of patients are warranted to determine long-term safety and efficacy."

Journal • Breast Cancer • Oncology • Solid Tumor • SOD2

Multi-omics analysis reveals the protective effects of Chinese yam polysaccharide against cisplatin-induced renal interstitial fibrosis. (PubMed, Phytomedicine) - "Our study showed that the alleviation of CDDP-induced RIF in vivo can be achieved through the inhibition of glycerophospholipid metabolism and PLD signaling pathways by SYDT."

Journal • Diabetic Nephropathy • Fibrosis • Immunology • Metabolic Disorders • Nephrology • Renal Disease • CTGF • MMP1 • VIM

Neuroprotective Effects of Amifostine in Mouse Model of Alzheimer's Disease. (PubMed, Clin Lab) - "Preconditioning with amifostine had a neuroprotective effect, maintained cognitive function, and enhanced cholinergic activity in the scopolamine-induced mouse model of Alzheimer's disease."

Biomarker • Clinical • Journal • Observational data • Preclinical • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • IL1B • IL6 • TNFA

A Comprehensive Narrative Review of the Impact of Pelvic Radiotherapy on Pelvic Bone Health: Pathophysiology, Early Diagnosis, and Prevention Strategies. (PubMed, Cureus) - "Some modalities, such as intensity-modulated radiotherapy (IMRT) and brachytherapy, have decreased fracture risk by escaping the adjacent structures to the targeted organ. Pharmacological interventions such as amifostine and desferrioxamine are promising in terms of bone protection, which necessitates further studies to confirm their mechanism of action."

Journal • Review • Gastrointestinal Disorder • Musculoskeletal Diseases • Oncology • Orthopedics • Vasculitis

N-formylmethionine-leucyl-phenylalanine protects against irradiation-induced damage to hematopoiesis and intestines. (PubMed, Mol Med) - "fMLP serves as a promising radioprotective agent, preserving cells and radiosensitive tissues from IR. Through its influence on the cell cycle, particularly reversing radiation-induced arrest in G2/M phases, fMLP offers protection against IR's detrimental effects."

Journal • Hematological Disorders

Acute kidney injury after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy - A systematic review. (PubMed, Eur J Surg Oncol) - "The highest incidence of AKI (45.45 %) was reported after paclitaxel-HIPEC. The incidence of AKI after cisplatin-HIPEC was 34.7 %...The perioperative use of sodium thiosulfate and amifostine led to a significant reduction in the incidence of AKI. The reported incidence of AKI after CRS-HIPEC is high. Identifying preoperative risk factors, optimising comorbidities, maintaining perioperative haemodynamic stability, perioperative use of sodium thiosulfate, maintaining adequate diuresis could reduce the incidence of AKI."

Journal • Review • Surgery • Acute Kidney Injury • Nephrology • Renal Disease

Second-generation piperazine derivatives as promising radiation countermeasures. (PubMed, RSC Med Chem) - "Despite the availability of compounds such as amifostine, their clinical utility is significantly limited by adverse side effects and logistical challenges in administration...Compound 6 emerged as the leading candidate, offering an optimal balance between efficacy and safety, with compound 3 also displaying significant potential. These findings support the further development and clinical evaluation of these compounds as safer, and more effective radiation countermeasures."

Journal • Hematological Malignancies • Leukemia • Oncology

Cisplatin and ototoxicity in childhood: the perspective of supporting otoprotective agentes. (PubMed, Braz J Biol) - "The substances found were: Amifostine, Dexamethasone, Genistein, Ginkgo Biloba, Lycopene, N-acetylcysteine, Polydatin also Sodium Thiosulfate. The biochemical effects of these substances are relevant to their potential otoprotective properties, including the inactivation of oxygen free radicals and electrophilic platinum species. The use of these substances can reduce ototoxicity, decreasing cisplatin-induced hearing loss and improving the confort of life, especially for children."

Journal • Review • Oncology • Otorhinolaryngology • Pediatrics

VALD-2 mitigates cisplatin-induced acute kidney injury: Mechanistic insights into oxidative stress modulation and inflammation suppression. (PubMed, J Biochem Mol Toxicol) - "The study involves daily intraperitoneal injections of amifostine or VALD-2 over 7 days to establish an AKI model. VALD-2 emerges as a promising mitigator of cisplatin-induced AKI, showcasing its ability to enhance oxidative stress-related protein expression. The findings suggest VALD-2 as a potential therapeutic agent for protecting against cisplatin-induced kidney injury."

Journal • Acute Kidney Injury • Inflammation • Nephrology • Oncology • Renal Disease • IL6 • TNFA

Serum miR-192-5p is a promising biomarker for lethal radiation injury. (PubMed, Toxicol Lett) - "In addition, it was found that among the 4 candidate serum miRNAs, only highly-expressed mmu-miR-192-5p in mouse serum irradiated at lethal doses was returned to sham-like expression levels at 3 days post-irradiation with amifostine pretreatment and closely correlated with survival rate. We demonstrated for the first time that mmu-miR-192-5p screened from lethally irradiated mice sera can be used as a potential biomarker for lethal irradiation injury, which will be helpful to improve efficiency of medical treatment to minimize casualties after a large-scale nuclear accident."

Biomarker • Journal • MIR192 • MIR194 • MIR223

Amifostine loaded lipid-calcium carbonate nanoparticles as an oral drug delivery system for radiation protection. (PubMed, Biomed Pharmacother) - "More importantly, we further investigated the cellular accumulation profile and intracellular transport mechanism of LCC/AMF using MDCK and Caco-2 cell lines as models. This research not only alters the current administration method of AMF to enhance its convenience and compliance, but also provides insights and guidance for the development of more suitable oral DDS for AMF in the future."

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