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ACS Applied Materials & Interfaces Mar 2023Radiation-induced brain injury (RIBI) is a severe, irreversible, or even life-threatening cerebral complication of radiotherapy in patients with head and neck tumors,...
Radiation-induced brain injury (RIBI) is a severe, irreversible, or even life-threatening cerebral complication of radiotherapy in patients with head and neck tumors, and there is no satisfying prevention and effective treatment available for these patients. Amifostine (AMF) is a well-known free radical scavenger with demonstrated effectiveness in preventing radiation-induced toxicity. However, the limited permeability of AMF across the blood-brain barrier (BBB) when administered intravenously reduces the effectiveness of AMF in preventing RIBI. Herein, we construct a nanoparticle (NP) platform for BBB delivery of AMF. AMF is conjugated with 1,2-dioleoyl--glycero-3-phosphoethanolamine--[poly(ethylene glycol)]-hydroxy succinamide [DSPE-PEG-NHS, PEG M 2000], and the product is DSPE-PEG-AMF. Then, the nanoparticles (DAPP NPs) were formed by self-assembly of poly(lactic--glycolic acid) (PLGA), DSPE-PEG-AMF, and polysorbate 80 (PS 80). PEG shields the nanoparticles from blood clearance by the reticuloendothelial system and lengthens the drug circulation time. PS 80 is used to encapsulate nanoparticles for medication delivery to the brain. The results of our study showed that DAPP NPs were able to effectively penetrate the blood-brain barrier (BBB) in healthy C57BL/6 mice. Furthermore, in a well-established mouse model of X-knife-induced brain injury, treatment with DAPP NPs (corresponding to 250 mg/kg AMF) was found to significantly reduce the volume of brain necrosis compared to mice treated with AMF (250 mg/kg). Importantly, the use of DAPP NPs was also shown to significantly mitigate the effects of radiation-induced neuronal damage and glial activation. This work presents a convenient brain-targeted AMF delivery system to achieve effective radioprotection for the brain, providing a promising strategy with tremendous clinical translation potential.
Topics: Mice; Animals; Blood-Brain Barrier; Amifostine; Mice, Inbred C57BL; Brain; Polyethylene Glycols; Polysorbates; Brain Injuries; Nanoparticles
PubMed: 36917732
DOI: 10.1021/acsami.3c00502 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Mar 2023This study aimed to examine whether two different doses of dexamethasone (DXM), which is a corticosteroid, and amifostine (AMI), which reduces cumulative tissue toxicity...
BACKGROUND
This study aimed to examine whether two different doses of dexamethasone (DXM), which is a corticosteroid, and amifostine (AMI), which reduces cumulative tissue toxicity induced by cisplatin in advanced-stage cancer patients, have ameliorative effects on pathologic changes associated with cardiac contusion (CC) induced in rats.
METHODS
Forty-two Wistar albino rats were equally divided into six groups (n=7): C, CC, CC+AMI 400, CC+AMI 200, CC+AMI+DXM, and CC+DXM. Tomography images and electrocardiographic analyzes were performed, mean arterial pressure was measured from the carotid artery, and blood and tissue samples were obtained for histopathological and biochemical analyses after trauma-induced CC.
RESULTS
While the total oxidant status and disulfide parameters in the cardiac tissue and serum were significantly higher (p<0.05), the total antioxidant status, total thiol, and native thiol parameters were significantly lower (p<0.01) in rats with trauma-induced CC. The most frequently observed finding in the electrocardiography analyze was ST elevation.
CONCLUSION
According to evaluation based on histological, biochemical, and electrocardiographic examinations, we believe that only 400 mg/kg dose of AMI or DXM can be effective in the treatment of myocardial contusion in rats. Evaluation based on histological findings.
Topics: Rats; Animals; Rats, Wistar; Thoracic Injuries; Amifostine; Wounds, Nonpenetrating; Heart Injuries; Myocardial Contusions
PubMed: 36880625
DOI: 10.14744/tjtes.2023.84308 -
ACS Applied Materials & Interfaces Mar 2023In response to diffused ionizing radiation damage throughout the body caused by nuclear leaks and inaccurate radiotherapy, radioprotectants with considerable free...
In response to diffused ionizing radiation damage throughout the body caused by nuclear leaks and inaccurate radiotherapy, radioprotectants with considerable free radical scavenging capacities, along with negligible adverse effects, are highly regarded. Herein, unlike being performed as toxic chemotherapeutic drug candidates, molybdenum-based polyoxometalate nanoclusters (Mo-POM NCs) were developed as a non-toxic potent radioprotectant with impressive free radical scavenging capacities for ionizing radiation protection. In comparison to the clinically used radioprotectant drug amifostine (AM), the as-prepared Mo-POM NCs exhibited effective shielding capacity by virtue of their antioxidant properties resulting from a valence shift of molybdenum ions, alleviating not only ionizing radiation-induced DNA damage but also disruption of the radiation-sensitive hematopoietic system. More encouragingly, without trouble with long-term retention in the body, ultra-small sized Mo-POM NCs prepared by the mimetic Folin-Ciocalteu assay can be removed from the body through the renal-urinary pathway and the hepato-enteral excretory system after completing the mission of radiation protection. This work broadened the biological applications of metal-based POM chemotherapeutic drugs to act as a neozoic radioprotectant.
Topics: Radiation-Protective Agents; Molybdenum; Radiation, Ionizing; Free Radicals
PubMed: 36702809
DOI: 10.1021/acsami.2c19282 -
European Review For Medical and... Dec 2022Sepsis is responsible for more than 5 million deaths worldwide every year. The purpose of this study was to use amifostine to reduce acute kidney injury developing as a...
OBJECTIVE
Sepsis is responsible for more than 5 million deaths worldwide every year. The purpose of this study was to use amifostine to reduce acute kidney injury developing as a result of sepsis.
MATERIALS AND METHODS
Thirty Sprague Dawley rats were divided into three equal groups - a healthy control group (Group 1), cecal ligation and puncture group (CLP, Group 2), and a CLP + amifostine (AMF) group receiving a total of 200 mg/kg AMF intraperitoneally (i.p.) 15 min before sepsis induction (Group 3).
RESULTS
Total thiol levels decreased while malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB/p65), and interleukin (IL)-1β, and IL-6 levels increased in the CLP group. We also observed degeneration in renal corpuscles, necrotic tubules, polymorphonuclear leukocyte inflammation, and vascular congestion. In the amifostine group, total thiol levels in tissue increased, while MDA, TNF-α, NF-кB/p65, IL-1β, and IL-6 levels, necrotic renal tubules, and inflammation decreased.
CONCLUSIONS
Amifostine prevented sepsis-related acute kidney injury by reducing inflammation and oxidative stress.
Topics: Rats; Animals; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Amifostine; Interleukin-6; Inflammation; Oxidative Stress; NF-kappa B; Acute Kidney Injury; Sepsis
PubMed: 36591826
DOI: 10.26355/eurrev_202212_30664 -
Human & Experimental Toxicology 2022This study aimed to elucidate the effects of amifostine (ethyol) (AM), a synthetic radioprotector, and red ginseng (RG), a natural radioprotective agent, against the...
This study aimed to elucidate the effects of amifostine (ethyol) (AM), a synthetic radioprotector, and red ginseng (RG), a natural radioprotective agent, against the toxic effect of ionizing radiation (IR) on kidney tissues through changes in biochemical and histopathological parameters in addition to contributions to the use of amifostine and RG in clinical studies Five groups were established: Group I (control, receiving only saline by gavage), Group II (IR only), and Group III (IR+AM, 200 mg/kg intraperitoneally (i.p.). Group IV (IR + RG, 200 mg/kg orally once a day for 4 weeks), and Group V (IR+RG+AM, 200 mg/kg orally once/day for 4 weeks before IR and 200 mg/kg AM administered (i.p.) 30 min before IR). All groups, except for the control group, were subject to 6-Gy whole-body IR in a single fraction. 24 h after irradiation, all animals were sacrificed under anesthesia. IR enhanced MDA, 8-OHdG, and caspase-3 expression while decreasing renal tissue GSH levels ( < .05). Significant numbers of necrotic tubules together with diffuse vacuolization in proximal and distal tubule epithelial cells were also observed. The examination also revealed substantial brush boundary loss in proximal tubules as well as relatively unusual glomerular structures. While GSH levels significantly increased in the AM, RG, and AM+RG groups, a decrease in KHDS, MDA, 8-OHdG, and caspase-3 expression was observed, compared to the group subject to IR only ( < .05). Therefore, reactive oxygen species-scavenging antioxidants may represent a promising treatment for avoiding kidney damage in patients receiving radiation.
Topics: Animals; Amifostine; Caspase 3; Kidney; Radiation, Ionizing; 8-Hydroxy-2'-Deoxyguanosine; Panax
PubMed: 36455263
DOI: 10.1177/09603271221143029 -
Journal of Toxicology and Environmental... Jan 2023The aim of this study was to determine accumulation of heavy metals and metalloids which are widely distributed in the environment and in food chain using wild edible...
The aim of this study was to determine accumulation of heavy metals and metalloids which are widely distributed in the environment and in food chain using wild edible mushrooms belonging to the Boletaceae family mushrooms. In addition, methanol extracts of mushrooms were tested for protective effect by the cytochalasin-B blocked micronucleus (CBMN) assay using chromosome aberrations in human peripheral lymphocytes as a model. The genotoxic activity of methanol extracts prepared at 4 different concentrations (1, 2, 3 or 6 µg/ml) was examined using amifostine and mitomycin C as positive controls. Extracts of species and exhibited the greatest reduction in the frequency of micronuclei (MN). Extract of at concentrations of 2 µg/ml showed the highest decrease in number of MN. In comparison, extract of mushroom at a concentration of 3 µg/ml displayed less reduction. However, as heavy metals and metalloids are found in mushrooms, another aim was to examine whether these agents affected genotoxicity. Principal component analysis (PCA) identified clustering differences between control and heavy metals and metalloids groups and might explain the influence of heavy element content and genotoxic activity in mushrooms.
Topics: Humans; Cadmium; Arsenic; Mercury; Agaricales; Serbia; Methanol; Lead; Metals, Heavy; Basidiomycota; Metalloids; DNA Damage
PubMed: 36445018
DOI: 10.1080/15287394.2022.2150992 -
International Journal of Radiation... 2023The intestine is a dose-limiting organ in the treatment of intra-abdominal cancer. We previously reported that the extract of mistletoe parasites on had a more potent...
PURPOSE
The intestine is a dose-limiting organ in the treatment of intra-abdominal cancer. We previously reported that the extract of mistletoe parasites on had a more potent radioprotective effect than amifostine in reducing the developmental toxicities of zebrafish embryos. In this study, radioprotection against intestinal toxicity was investigated in adult zebrafish.
METHODS
Wild-type adult AB zebrafish were exposed to 45-50 Gy of photon beam irradiation and/or treated with mistletoe extract orally 1 h before. The main endpoints of the study were survival and degree of deformation of the intestinal villi.
RESULTS
The median follow-up period was 10 d post-irradiation (range: 7-11 d). A total of 105 zebrafish were used, including 42 in the radiation alone, 42 in the radiation and mistletoe arms, and 21 control subjects (mistletoe alone, mock-irradiated arm). The rate of both significant deformity and death was 53% in the radiation-alone arm, whereas the corresponding rate was 30% in the radiation and mistletoe arms. Significant deformity-free survival rates at 10 d post-irradiation in the radiation alone, and radiation and mistletoe arms were 44.7% (95% confidence interval [CI]:20-54.3) and 68.4% (95% CI:53.8-86.8), respectively (=.046). The radiation and mistletoe arms showed decreased expression of two of three inflammatory genes () compared to the radiation alone group (<.05).
CONCLUSION
The radioprotective effect against intestinal toxicity was successfully shown in an adult zebrafish model. This result suggests the possibility of clinical use of mistletoe extract for the treatment of abdominal cancers.
Topics: Animals; Zebrafish; Amifostine; Plant Extracts; Mistletoe; Intestines; Radiation-Protective Agents
PubMed: 36318746
DOI: 10.1080/09553002.2023.2142982 -
Archives of Pharmacal Research Oct 2022Chemotherapy is a main treatment for cancer, and it benefits patients by controlling cancer relapse and metastasis, thereby leading to an increase in the overall... (Review)
Review
Chemotherapy is a main treatment for cancer, and it benefits patients by controlling cancer relapse and metastasis, thereby leading to an increase in the overall survival rate. However, this treatment is associated with mild to severe side effects, one of which is cardiotoxicity. The severity of cardiotoxicity, a leading cause of cardiovascular diseases, depends on the type of cancer therapy employed and the time required for its management. A chemotherapeutic agent is used either alone or in combination with other drugs for cancer treatment. The exact mechanism of chemotherapeutic agent-induced cardiotoxicity remains unclear, although it is likely to be multifactorial and to include oxidative stress, apoptosis, and inflammation. There are many approaches to avoid the untoward effects of chemotherapeutic agents. However, the available options for cardiac protection are minimal, and they include renin-angiotensin system blockers, beta-blockers, herbal drugs, or iron chelators such as dexrazoxane. The present review provides information on the molecular mechanism of chemotherapy-induced myocardial infarction and cardiotoxicity along with scientifically studied synthetic molecules, herbal extracts, and natural products to manage chemotherapy-induced cardiotoxicity.
Topics: Humans; Cardiotoxicity; Antineoplastic Agents; Heart; Neoplasms; Oxidative Stress; Cardiotonic Agents
PubMed: 36306018
DOI: 10.1007/s12272-022-01411-4 -
Acta Biomaterialia Nov 2022
PubMed: 36266204
DOI: 10.1016/j.actbio.2022.10.010 -
Advanced Healthcare Materials Jan 2023Clinical wound management of radiation-induced skin injury (RSI) remains a great challenge due to acute injuries induced by excessive reactive oxygen species (ROS), and...
Clinical wound management of radiation-induced skin injury (RSI) remains a great challenge due to acute injuries induced by excessive reactive oxygen species (ROS), and the concomitant repetitive inflammatory microenvironment caused by an imbalance in macrophage homeostasis. Herein, a cutaneous extracellular matrix (ECM)-inspired glycopeptide hydrogel (GK@TA ) is rationally designed for accelerating wound healing through modulating the chronic inflammation in RSI. The glycopeptide hydrogel not only replicates ECM-like glycoprotein components and nanofibrous architecture, but also displays effective ROS scavenging and radioprotective capability that can reduce the acute injuries after exposure to irradiation. Importantly, the mannose receptor (MR) in GK@TA exhibits high affinity and bioactivity to drive the M2 macrophage polarization, thereby overcoming the persistent inflammatory microenvironment in chronic RSI. The repair of RSI in mice demonstrates that GK@TA significantly reduces the hyperplasia of epithelial, promotes appendage regeneration and angiogenesis, and decreased the proinflammatory cytokine expression, which is superior to the treatment of commercial radioprotective drug amifostine. Collectively, the ECM-mimetic hydrogel dressing can protect the tissue from irradiation and heal the chronic wound in RSI, holding great potential in clinical wound management and tissue regeneration.
Topics: Animals; Mice; Hydrogels; Reactive Oxygen Species; Wound Healing; Skin; Inflammation
PubMed: 36183357
DOI: 10.1002/adhm.202201671