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International Journal of Preventive... 2017Children with cancer treated with cytotoxic drugs are frequently at risk of developing renal dysfunction. The cytotoxic drugs that are widely used for cancer treatment... (Review)
Review
Children with cancer treated with cytotoxic drugs are frequently at risk of developing renal dysfunction. The cytotoxic drugs that are widely used for cancer treatment in children are cisplatin (CPL), ifosfamide (IFO), carboplatin, and methotrexate (MTX). Mechanisms of anticancer drug-induced renal disorders are different and include acute kidney injury (AKI), tubulointerstitial disease, vascular damage, hemolytic uremic syndrome (HUS), and intrarenal obstruction. CPL nephrotoxicity is dose-related and is often demonstrated with hypomagnesemia, hypokalemia, and impaired renal function with rising serum creatinine and blood urea nitrogen levels. CPL, mitomycin C, and gemcitabine treatment cause vascular injury and HUS. High-dose IFO, streptozocin, and azacitidine cause renal tubular dysfunction manifested by Fanconi syndrome, rickets, and osteomalacia. AKI is a common adverse effect of MTX, interferon-alpha, and nitrosourea compound treatment. These strategies to reduce the cytotoxic drug-induced nephrotoxicity should include adequate hydration, forced diuresis, and urinary alkalization. Amifostine, sodium thiosulfate, and diethyldithiocarbamate provide protection against CPL-induced renal toxicity.
PubMed: 29114374
DOI: 10.4103/ijpvm.IJPVM_40_17 -
Oxidative Medicine and Cellular... 2016Cytoprotectant amifostine attenuates radiation-induced oxidative injury by increasing intracellular manganese superoxide dismutase (SOD2) in peripheral tissue. However,...
BACKGROUND
Cytoprotectant amifostine attenuates radiation-induced oxidative injury by increasing intracellular manganese superoxide dismutase (SOD2) in peripheral tissue. However, whether amifostine could protect neuronal cells against oxidative injury has not been reported. The purpose of this study is to explore the protection of amifostine in PC12 cells.
METHODS
PC12 cells exposed to glutamate were used to mimic neuronal oxidative injury. SOD assay kit was taken to evaluate intracellular Cu/Zn SOD (SOD1) and SOD2 activities; western blot analysis and immunofluorescence staining were performed to investigate SOD2 protein expression; MTT, lactate dehydrogenase (LDH), release and cell morphology were used to evaluate cell injury degree, and apoptotic rate and cleaved caspase-3 expression were taken to assess apoptosis; mitochondrial superoxide production, intracellular reactive oxygen species (ROS), and glutathione (GSH) and catalase (CAT) levels were evaluated by reagent kits.
RESULTS
Amifostine increased SOD2 activity and expression, decreased cell injury and apoptosis, reduced mitochondrial superoxide production and intracellular ROS generation, and restored intracellular GSH and CAT levels in PC12 cells exposed to glutamate. SOD2-siRNA, however, significantly reversed the amifostine-induced cytoprotective and antioxidative actions.
CONCLUSION
SOD2 mediates amifostine-induced protection in PC12 cells exposed to glutamate.
Topics: Amifostine; Animals; Apoptosis; Catalase; Glutamic Acid; Glutathione; Intracellular Space; Mitochondria; Models, Biological; Neuroprotection; PC12 Cells; RNA, Small Interfering; Rats; Reactive Oxygen Species; Superoxide Dismutase; Superoxides; Up-Regulation
PubMed: 26770652
DOI: 10.1155/2016/4202437 -
Brazilian Journal of Medical and... Feb 2019Oral mucositis (OM) is a common and dose-limiting side effect of cancer treatment, including 5-fluorouracil (5-FU) and radiotherapy. The efficacy of the therapeutic...
Oral mucositis (OM) is a common and dose-limiting side effect of cancer treatment, including 5-fluorouracil (5-FU) and radiotherapy. The efficacy of the therapeutic measures to prevent OM is limited and disease prevention is not fully observable. Amifostine is a cytoprotective agent with a described anti-inflammatory potential. It is clinically used to reduce radiotherapy and chemotherapy-associated xerostomia. This study investigated the protective effect of amifostine on an experimental model of OM. Hamsters were divided into six groups: saline control group (5 mL/kg), mechanical trauma (scratches) of the right cheek pouch; 5-FU (60 and 40 mg/kg, ip, respectively, administered on days 1 and 2); amifostine (12.5, 25, or 50 mg/kg) + 5-FU + scratches. Salivation rate was assessed and the animals were euthanized on day 10 for the analysis of macroscopic and microscopic injury by scores. Tissue samples were harvested for the measurement of neutrophil infiltration and detection of inflammatory markers by ELISA and immunohistochemistry. 5-FU induced pronounced hyposalivation, which was prevented by amifostine (P<0.05). In addition, 5-FU injection caused pronounced tissue injury accompanied by increased neutrophil accumulation, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) tissue levels, and positive immunostaining for TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Interestingly, amifostine prevented the inflammatory reaction and consequently improved macroscopic and microscopic damage (P<0.05 vs 5-FU group). Amifostine reduced inflammation and protected against 5-FU-associated oral mucositis and hyposalivation.
Topics: Amifostine; Animals; Cricetinae; Disease Models, Animal; Fluorouracil; Inflammation; Male; Protective Agents; Stomatitis; Xerostomia
PubMed: 30810625
DOI: 10.1590/1414-431X20188251 -
Translational Oncology Jun 2018The first tenet of medicine, "primum non nocere" or "first, do no harm", is not always compatible with oncological interventions e.g., chemotherapy, targeted therapy and... (Review)
Review
The first tenet of medicine, "primum non nocere" or "first, do no harm", is not always compatible with oncological interventions e.g., chemotherapy, targeted therapy and radiation, since they commonly result in significant toxicities. One of the more frequent and serious treatment-induced toxicities is mucositis and particularly oral mucositis (OM) described as inflammation, atrophy and breakdown of the mucosa or lining of the oral cavity. The sequelae of oral mucositis (OM), which include pain, odynodysphagia, dysgeusia, decreased oral intake and systemic infection, frequently require treatment delays, interruptions and discontinuations that not only negatively impact quality of life but also tumor control and survivorship. One potential strategy to reduce or prevent the development of mucositis, for which no effective therapies exist only best supportive empirical care measures, is the administration of agents referred to as radioprotectors and/or chemoprotectors, which are intended to differentially protect normal but not malignant tissue from cytotoxicity. This limited-scope review briefly summarizes the incidence, pathogenesis, symptoms and impact on patients of OM as well as the background and mechanisms of four clinical stage radioprotectors/chemoprotectors, amifostine, palifermin, GC4419 and RRx-001, with the proven or theoretical potential to minimize the development of mucositis particularly in the treatment of head and neck cancers.
PubMed: 29698934
DOI: 10.1016/j.tranon.2018.03.014 -
Iranian Journal of Basic Medical... 2023Acrylamide (ACR) is a toxic chemical agent that can induce hepatotoxicity through different mechanisms including oxidative stress and apoptosis. Amifostine is an...
OBJECTIVES
Acrylamide (ACR) is a toxic chemical agent that can induce hepatotoxicity through different mechanisms including oxidative stress and apoptosis. Amifostine is an important hepatoprotective and anti-oxidant compound. In this research, the hepatoprotective effect of amifostine on ACR-induced hepatotoxicity in rats has been investigated.
MATERIALS AND METHODS
Male Wistar rats were randomly divided into 7 groups, including: 1. Control group, 2. ACR (50 mg/kg, 11 days, IP), 3-5. ACR+ amifostine (25, 50, 100 mg/kg, 11 days, IP), 6. ACR+ N-acetyl cysteine (NAC) (200 mg/kg, 11 days, IP), and 7. Amifostine (100 mg/kg, 11 days, IP). At the end of the injection period, animals' liver samples were collected to determine the content of glutathione (GSH), malondialdehyde (MDA), and apoptotic proteins (B-cell lymphoma 2 (Bcl2), Bcl-2-associated X protein (Bax), and cleaved caspase-3. Serum samples were also collected to measure alanine transaminase (ALT) and aspartate transaminase (AST) levels.
RESULTS
Administration of ACR increased MDA, Bax/Bcl2 ratio, cleaved caspase-3, ALT, and AST levels, and decreased GSH content compared with the control group. The administration of amifostine with ACR decreased MDA, Bax/Bcl2 ratio, cleaved caspase-3, ALT, and AST levels, and increased GSH content compared with the ACR group. Receiving NAC along with ACR reversed the alterations induced by ACR.
CONCLUSION
This study shows that pretreatment with amifostine can reduce ACR-induced toxicity in the liver tissue of rats. Since oxidative stress is one of the most important mechanisms in ACR toxicity, amifostine probably reduces the toxicity of ACR by increasing the anti-oxidant and anti-apoptotic capacity of the hepatic cells.
PubMed: 37275759
DOI: 10.22038/IJBMS.2023.67815.14837 -
Asian Pacific Journal of Cancer... Sep 2022Amifostine is a powerful antioxidant that is one of the documented three chemo-radio prototectants recommended for clinical use. There is no data exploring amifostine in...
BACKGROUND
Amifostine is a powerful antioxidant that is one of the documented three chemo-radio prototectants recommended for clinical use. There is no data exploring amifostine in prevention of acute pericardial damage. We aimed to investigate whether amifostine has protective effect against acute pericardial injury due to radiotherapy in an experimental rat model.
METHODS
Twenty-four rats were divided into four groups: control group, radiotherapy-only group, amifostine-only group, radiotherapy+amifostine group. In groups receiving radiotherapy, hearts were irradiated with a Co 60 teletherapy device at a distance of 80 cm and 20 Gy at a depth of 2 cm. Thirty minutes before interventions, 200 mg/kg amifostine or same volume 0.9% NaCl were administered intraperitoneally. Subjects were sacrificed 24 hours after the procedure. Pericardial histopathological changes were investigated by light microscopy.
RESULTS
There was focal inflammation of >= 50% in all rats exposed-to-radiotherapy. All groups receiving radiotherapy revealed a significant increase in pericardial inflammation compared to the groups that did not receive irradiation (p<0.05). There was no difference between the radiotherapy-only group and amifostine+radiotherapy group for pericardial inflammatory response (p>0.05).
CONCLUSION
Acute pericarditis was detected in all rats receiving radiotherapy. There was no positive effect of amifostine administration before radiotherapy on acute pericardial inflammation.
Topics: Amifostine; Animals; Antioxidants; Inflammation; Pericarditis; Radiation Injuries; Radiation-Protective Agents; Rats; Saline Solution
PubMed: 36172686
DOI: 10.31557/APJCP.2022.23.9.3209 -
Journal of Clinical and Experimental... Apr 2016The management of oral mucositis is a challenge, due to its complex biological nature. Over the last 10 years, different strategies have been developed for the... (Review)
Review
INTRODUCTION
The management of oral mucositis is a challenge, due to its complex biological nature. Over the last 10 years, different strategies have been developed for the management of oral mucositis caused by chemotherapy in cancer patients.
MATERIAL AND METHODS
An exhaustive search was made of the PubMed-Medline, Cochrane Library and Scopus databases, crossing the key words "oral mucositis", "prevention" and "treatment" with the terms "chemotherapy" and "radiotherapy" by means of the boolean operators "AND" and "NOT". A total of 268 articles were obtained, of which 96 met the inclusion criteria.
RESULTS
Several interventions for the prevention of oral mucositis, such as oral hygiene protocols, amifostine, benzidamine, calcium phosphate, cryotherapy and iseganan, among others, were found to yield only limited benefits. Other studies have reported a decrease in the appearance and severity of mucositis with the use of cytoprotectors (sucralfate, oral glutamine, hyaluronic acid), growth factors, topical polyvinylpyrrolidone, and low power laser irradiation.
CONCLUSIONS
Very few interventions of confirmed efficacy are available for the management of oral mucositis due to chemotherapy. However, according to the reviewed literature, the use of palifermin, cryotherapy and low power laser offers benefits, reducing the incidence and severity of oral mucositis - though further studies are needed to confirm the results obtained.
KEY WORDS
Chemotherapy-Induced Oral Mucositis Treatment.
PubMed: 27034762
DOI: 10.4317/jced.52917 -
World Journal of Clinical Oncology Jan 2019Xerostomia, or dry mouth, is a significant problem affecting quality of life in patients treated with radiation therapy for head and neck cancer. Strategies for... (Review)
Review
Xerostomia, or dry mouth, is a significant problem affecting quality of life in patients treated with radiation therapy for head and neck cancer. Strategies for reduction of xerostomia burden vary widely, with options including: sialagogue medications, saliva substitutes, acupuncture, vitamins, hyperbaric oxygen, submandibular gland transfer, and acupuncture or associated treatments. In this review, we sought to evaluate long-term outcomes of patients treated with various interventions for radiation-induced xerostomia. A literature search was performed using the terms "xerostomia" and "radiation" or "radiotherapy"; all prospective clinical trials were evaluated, and only studies that reported 1 year follow up were included. The search results yielded 2193 studies, 1977 of which were in English. Of those, 304 were clinical trials or clinical studies. After abstract review, 23 trials were included in the review evaluating the following treatment modalities: pilocarpine (three); cevimeline (one); amifostine (eleven); submandibular gland transfer (five); acupuncture like transcutaneous electrical nerve stimulation (ALTENS) (one); hyperbaric oxygen (one); and acupuncture (one). Pilocarpine, cevimeline, and amifostine have been shown in some studies to improve xerostomia outcomes, at the cost of toxicity. ALTENS has similar efficacy with fewer side effects. Submandibular gland transfer is effective but requires an elective surgery, and thus may not always be appropriate or practical. The use of intensity-modulated radiation therapy, in addition to dose de-escalation in select patients, may result in fewer patients with late xerostomia, reducing the need for additional interventions.
PubMed: 30627521
DOI: 10.5306/wjco.v10.i1.1 -
World Journal of Gastrointestinal... Feb 2015Pelvic cancers are among the most frequently diagnosed cancers worldwide. Treatment of patients requires a multidisciplinary approach that frequently includes... (Review)
Review
Pelvic cancers are among the most frequently diagnosed cancers worldwide. Treatment of patients requires a multidisciplinary approach that frequently includes radiotherapy. Gastrointestinal (GI) radiation-induced toxicity is a major complication and the transient or long-term problems, ranging from mild to very severe, arising in non-cancerous tissues resulting from radiation treatment to a tumor of pelvic origin, are actually called as pelvic radiation disease. The incidence of pelvic radiation disease changes according to the radiation technique, the length of follow up, the assessment method, the type and stage of cancer and several other variables. Notably, even with the most recent radiation techniques, i.e., intensity-modulated radiotherapy, the incidence of radiation-induced GI side effects is overall reduced but still not negligible. In addition, radiation-induced GI side effects can develop even after several decades; therefore, the improvement of patient life expectancy will unavoidably increase the risk of developing radiation-induced complications. Once developed, the management of pelvic radiation disease may be challenging. Therefore, the prevention of radiation-induced toxicity represents a reasonable way to avoid a dramatic drop of the quality of life of these patients. In the current manuscript we provide an updated and practical review on the best available evidences in the field of the prevention of pelvic radiation disease.
PubMed: 25664197
DOI: 10.4292/wjgpt.v6.i1.1 -
The Oncologist Apr 2015Neurotoxicity is a burdensome side effect of platinum-based chemotherapy that prevents administration of the full efficacious dosage and often leads to treatment... (Review)
Review
Neurotoxicity is a burdensome side effect of platinum-based chemotherapy that prevents administration of the full efficacious dosage and often leads to treatment withdrawal. Peripheral sensory neurotoxicity varies from paresthesia in fingers to ataxic gait, which might be transient or irreversible. Because the number of patients being treated with these neurotoxic agents is still increasing, the need for understanding the pathogenesis of this dramatic side effect is critical. Platinum derivatives, such as cisplatin and carboplatin, harm mainly peripheral nerves and dorsal root ganglia neurons, possibly because of progressive DNA-adduct accumulation and inhibition of DNA repair pathways (e.g., extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase/stress-activated protein kinase, and p38 mitogen-activated protein kinass), which finally mediate apoptosis. Oxaliplatin, with a completely different pharmacokinetic profile, may also alter calcium-sensitive voltage-gated sodium channel kinetics through a calcium ion immobilization by oxalate residue as a calcium chelator and cause acute neurotoxicity. Polymorphisms in several genes, such as voltage-gated sodium channel genes or genes affecting the activity of pivotal metal transporters (e.g., organic cation transporters, organic cation/carnitine transporters, and some metal transporters, such as the copper transporters, and multidrug resistance-associated proteins), can also influence drug neurotoxicity and treatment response. However, most pharmacogenetics studies need to be elucidated by robust evidence. There are supportive reports about the effectiveness of several neuroprotective agents (e.g., vitamin E, glutathione, amifostine, xaliproden, and venlafaxine), but dose adjustment and/or drug withdrawal seem to be the most frequently used methods in the management of platinum-induced peripheral neurotoxicity. To develop alternative options in the treatment of platinum-induced neuropathy, studies on in vitro models and appropriate trials planning should be integrated into the future design of neuroprotective strategies to find the best patient-oriented solution.
Topics: Antineoplastic Agents; Humans; Neuroprotective Agents; Neurotoxicity Syndromes; Pharmacogenetics; Platinum Compounds; Polymorphism, Genetic
PubMed: 25765877
DOI: 10.1634/theoncologist.2014-0044