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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 -
Journal of Veterinary Science May 2023Titanium is the most widely used metal for bone integration, especially for cancer patients receiving ionizing radiation. This study aimed to investigate the amifostine...
BACKGROUND
Titanium is the most widely used metal for bone integration, especially for cancer patients receiving ionizing radiation. This study aimed to investigate the amifostine administration that would reduce the effects of radiation on bone healing and osseointegration in rat models.
OBJECTIVES
It is aimed that the application of amifostine in rats receiving radiotherapy treatment will reduce the negative effects of ionizing radiation on the bone.
METHODS
Thirty-five adult male Wistar rats were randomly divided into one healthy and four experimental groups. In three consecutive days, two experimental groups of rats (AMF-RT-IMP and RT-IMP) were exposed to radiation (15 Gy/3 fractions of 5 Gy each). Then the titanium implants were inserted into the left tibia. Before the radiotherapy process, a 200 mg/kg dose of amifostine (AMF) was administered to the rats in the AMF-IMP and AMF-RT-IMP groups. Twenty-eight days after the screw implant, all rats were sacrificed, and their blood samples and tibia bones were collected for analysis.
RESULTS
The results indicated an accelerated bone formation and a more rapid healing process in the screw implants in the AMF-IMP, AMF-RT-IMP, and AMF-RT groups than in the RT-IMP group. Also, bone-implant contact area measurement and inflammation decreased with amifostine treatment in the implants subjected to irradiation ( < 0.05).
CONCLUSIONS
The results obtained in the present study suggested that amifostine prevents the losses of bone minerals, bone integrity, and implant position from ionizing-radiation when given before exposure.
Topics: Rats; Male; Animals; Amifostine; Tibia; Titanium; Radiation-Protective Agents; Rats, Wistar
PubMed: 37271503
DOI: 10.4142/jvs.23023 -
Current Oncology (Toronto, Ont.) Apr 2023Despite high incidence rates and severe complications, the management of xerostomia lacks clinical guidelines. The aim of this overview was to summarize the clinical... (Review)
Review
Despite high incidence rates and severe complications, the management of xerostomia lacks clinical guidelines. The aim of this overview was to summarize the clinical experience derived from the last 10 years of treatments and prevention using systemic compounds. Results showed that the cytoprotective drug amifostine, and its antioxidant agents, are the most discussed as preventive agents of xerostomia in head and neck cancer (HNC) patients. In the presence of the disease, the pharmacological treatments have been mainly directed to stimulate secretion of the damaged salivary glands, or to counteract a decreased capacity of the antioxidant system, in view of an increasing of reactive oxygen species (ROS). However, the data demonstrated low ability of the drugs, together with a great number of side effects, which strongly limit their use. Concerning traditional medicine (TM), valid clinical trials are so limited that neither the efficacy nor the absence of interferences to concomitant chemical therapies can be validated. Consequently, the management of xerostomia and its devastating complications remain a very significant void in daily clinical practice.
Topics: Humans; Radiation-Protective Agents; Antioxidants; Xerostomia; Amifostine; Medicine, Traditional
PubMed: 37232794
DOI: 10.3390/curroncol30050336 -
Phytomedicine : International Journal... Jul 2023Activation of renal fibroblasts into myofibroblasts plays an important role in promoting renal interstitial fibrosis (RIF). Ginkgo biloba extract (EGb) can alleviate RIF...
Ginkgo biloba extract attenuates cisplatin-induced renal interstitial fibrosis by inhibiting the activation of renal fibroblasts through down-regulating the HIF-1α/STAT3/IL-6 pathway in renal tubular epithelial cells.
BACKGROUND
Activation of renal fibroblasts into myofibroblasts plays an important role in promoting renal interstitial fibrosis (RIF). Ginkgo biloba extract (EGb) can alleviate RIF induced by cisplatin (CDDP).
PURPOSE
To elucidate the effect of EGb treatment on cisplatin-induced RIF and reveal its potential mechanism.
METHODS
The two main active components in EGb were determined by high-performance liquid chromatography (HPLC) analysis. Rats were induced by CDDP and then treated with EGb, 2ME2 (HIF-1α inhibitor) or amifostine. After HK-2 cells and HIF-1α siRNA HK-2 cells were treated with CDDP, EGb or amifostine, the conditioned medium from each group was cultured with NRK-49F cells. The renal function of rats was detected. The renal damage and fibrosis were evaluated by H&E and Masson trichrome staining. The IL-6 content in the cell medium was detected by ELISA. The expression levels of indicators related to renal fibrosis and signaling pathway were examined by western blotting and qRT-PCR.
RESULTS
HPLC analysis showed that the contents of quercetin and kaempferol in EGb were 36.0 μg/ml and 45.7 μg/ml, respectively. In vivo, EGb and 2ME2 alleviated renal damage and fibrosis, as well as significantly decreased the levels of α-SMA, HIF-1α, STAT3 and IL-6 in rat tissues induced by CDDP. In vitro, the levels of HIF-1α, STAT3 and IL-6 were significantly increased in HK-2 cells and HIF-1α siRNA HK-2 cells induced by CDDP. Notably, HIF-1α siRNA significantly decreased the levels of HIF-1α, STAT3 and IL-6 in HK-2 cells, as well as the IL-6 level in medium from HK-2 cells. Additionally, the α-SMA level in NRK-49F cells was significantly increased after being cultured with conditioned medium from HK-2 cells or HIF-1α siRNA HK-2 cells exposed to CDDP. Furthermore, exogenous IL-6 increased the α-SMA level in NRK-49F cells. Importantly, the expression levels of the above-mentioned indicators were significantly decreased after the HK-2 cells and HIF-1α siRNA HK-2 cells were treated with EGb.
CONCLUSION
This study revealed that EGb improves CDDP-induced RIF, and the mechanism may be related to its inhibition of the renal fibroblast activation by down-regulating the HIF-1α/STAT3/IL-6 pathway in renal tubular epithelial cells.
Topics: Rats; Animals; Cisplatin; Interleukin-6; Amifostine; Culture Media, Conditioned; Kidney; Kidney Diseases; Ginkgo biloba; Fibroblasts; RNA, Small Interfering; Fibrosis; Epithelial Cells
PubMed: 37087791
DOI: 10.1016/j.phymed.2023.154809 -
Frontiers in Immunology 2023Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are...
BACKGROUND
Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease.
METHODS
Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade lower genital tract dysplasia. Anorectal tumor swabs were prospectively collected from patients with biopsy-confirmed locally advanced SCCA prior to receiving standard-of-care chemoradiotherapy (CRT). Patients with high-grade lower genital tract dysplasia without anal dysplasia were considered high-risk (HR Normal). 16S V4 rRNA Microbiome sequencing was performed for anal swabs. Alpha and Beta Diversity and composition were compared for HR Normal, anal dysplasia, and anal cancer.
RESULTS
60 patients with high-grade lower genital tract dysplasia were initially enrolled. Seven patients had concurrent anal dysplasia and 44 patients were considered HR Normal. Anorectal swabs from 21 patients with localized SCCA were included, sequenced, and analyzed in the study. Analysis of weighted and unweighted UniFrac distances demonstrated significant differences in microbial community composition between anal cancer and HR normal (p0.018). LEfSe identified that all three groups exhibited differential enrichment of specific taxa. (p=0.028), (p=0.0295) (p=0.034) (p=0.029) were enriched in anal cancer specimens when compared to HR normal.
CONCLUSION
Although alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased anorectal , , and abundance were associated with anal cancer. These organisms have been reported in various gastrointestinal cancers with roles in facilitating the proinflammatory microenvironment and neoplasia progression. Future work should investigate a potential role of microbiome analysis in screening for anal dysplasia and investigation into potential mechanisms of how these microbial imbalances influence the immune system and anal carcinogenesis.
Topics: Humans; Female; Papillomavirus Infections; Prospective Studies; Cross-Sectional Studies; Anus Neoplasms; Carcinoma, Squamous Cell; Microbiota; Tumor Microenvironment
PubMed: 37063829
DOI: 10.3389/fimmu.2023.1051431 -
International Journal of Biological... Jun 2023Ionizing radiation-induced injury commonly happens in radiotherapy, leading to damages of the hematopoietic and gastrointestinal systems. Radioprotective medications are...
Ionizing radiation-induced injury commonly happens in radiotherapy, leading to damages of the hematopoietic and gastrointestinal systems. Radioprotective medications are mainly applied in hospitals, although only injections are available and their gut protection is limited. Here, oral konjac glucomannan (KGM), a natural macromolecule and soluble dietary fiber, was used against ionizing radiation-induced injury. The mice were fed with KGM (0.4 g/kg) for 3 days or injected with a clinical medication amifostine before 6.5 Gy γ-ray whole body irradiation (WBI) or 13 Gy whole abdominal irradiation (WAI). In the WBI experiments, KGM improved blood cell recovery and bone marrow cell proliferation in the femur and spleen, though its effect was weaker than or similar to that of amifostine. In the WBI experiments, the gut protection of KGM was similar to or a little better than that of amifostine, involving regenerated crypts numbers, villus length, and gut permeability. Moreover, KGM remarkably enhanced the survival rates of WBI and WAI mice, consistent with amifostine. KGM, as a prebiotic, enhanced gut microbiota abundance, probiotic numbers, and short chain fatty acid production, maintaining gut homeostasis. Moreover, KGM inhibited the apoptosis of irradiated human intestinal epithelial cells. KGM is a promising natural macromolecule against ionizing radiation-induced injury.
Topics: Humans; Mice; Animals; Amifostine; Gastrointestinal Microbiome; Fatty Acids, Volatile; Gamma Rays
PubMed: 37044326
DOI: 10.1016/j.ijbiomac.2023.124402 -
Biomolecules Mar 2023The radiation protection strategy with chemical agents has long been based on an antioxidative approach consisting in reducing the number of radical oxygen and nitrogen...
Molecular Influence of the ATM Protein in the Treatment of Human Cells with Different Radioprotective Drugs: Comparisons between Antioxidative and Pro-Episkevic Strategies.
The radiation protection strategy with chemical agents has long been based on an antioxidative approach consisting in reducing the number of radical oxygen and nitrogen species responsible for the formation of the radiation-induced (RI) DNA damage, notably the DNA double-strand breaks (DSB), whose subset participates in the RI lethal effect as unrepairable damage. Conversely, a DSB repair-stimulating strategy that may be called the "pro-episkevic" approach (from the ancient Greek , meaning repair) can be proposed. The pro-episkevic approach directly derives from a mechanistic model based on the RI nucleoshuttling of the ATM protein (RIANS) and contributes to increase the number of DSB managed by NHEJ, the most predominant DSB repair and signaling pathway in mammalians. Here, three radioresistant and three radiosensitive human fibroblast cell lines were pretreated with antioxidative agents (N-acetylcysteine or amifostine) or to two pro-episkevic agents (zoledronate or pravastatin or both (ZOPRA)) before X-ray irradiation. The fate of the RI DSB was analyzed by using γH2AX and pATM immunofluorescence. While amifostine pretreatment appeared to be the most efficient antioxidative process, ZOPRA shows the most powerful radiation protection, suggesting that the pro-episkevic strategy may be an alternative to the antioxidative one. Additional investigations are needed to develop some new drugs that may elicit both antioxidative and pro-episkevic properties and to quantify the radiation protection action of both types of drugs applied concomitantly.
Topics: Animals; Humans; Ataxia Telangiectasia Mutated Proteins; Radiation-Protective Agents; DNA Breaks, Double-Stranded; Antioxidants; Amifostine; DNA Repair; Mammals
PubMed: 36979459
DOI: 10.3390/biom13030524 -
Acta Pharmaceutica Sinica. B Mar 2023Radiation protection drugs are often accompanied by toxicity, even amifostine, which has been the dominant radio-protecting drug for nearly 30 years. Furthermore, there...
Radiation protection drugs are often accompanied by toxicity, even amifostine, which has been the dominant radio-protecting drug for nearly 30 years. Furthermore, there is no therapeutic drug for radiation-induced intestinal injury (RIII). This paper intends to find a safe and effective radio-protecting ingredient from natural sources. The radio-protecting effect of Ecliptae Herba (EHE) was discovered preliminarily by antioxidant experiments and the mouse survival rate after Cs irradiation. EHE components and blood substances were identified through UPLC‒Q-TOF. The correlation network of "natural components in EHE-constituents migrating to blood-targets-pathways" was established to predict the active components and pathways. The binding force between potential active components and targets was studied by molecular docking, and the mechanism was further analyzed by Western blotting, cellular thermal shift assay (CETSA), and ChIP. Additionally, the expression levels of Lgr5, Axin2, Ki67, lysozyme, caspase-3, caspase-8,8-OHdG, and p53 in the small intestine of mice were detected. It was found for the first time that EHE is active in radiation protection and that luteolin is the material basis of this protection. Luteolin is a promising candidate for RⅢ. Luteolin can inhibit the p53 signaling pathway and regulate the BAX/BCL2 ratio in the process of apoptosis. Luteolin could also regulate the expression of multitarget proteins related to the same cell cycle.
PubMed: 36970216
DOI: 10.1016/j.apsb.2022.09.003 -
Journal of Oncology 2023Osteoradionecrosis (ORN) is described as a disease with exposed, nonviable bone that fails to heal spontaneously or by means of conservative treatment after radiotherapy... (Review)
Review
Osteoradionecrosis (ORN) is described as a disease with exposed, nonviable bone that fails to heal spontaneously or by means of conservative treatment after radiotherapy in at least 3 months. Though traditional theories in the early stage including hypoxic-hypocellular-hypovascular and fibro-atrophic in addition to new findings such as ferroptosis were put forward to explain the mechanisms of the osteoradionecrosis, the etiology of ORN is still unclear. With the high rate of occurrence in the head and neck area, especially in the mandible, this disease can disrupt the shape and function of the irradiated area, leading to a clinical presentation ranging from stable small areas of asymptomatic exposed bone to severe progressive necrosis. In severe cases, patients may experience pain, xerostomia, dysphagia, facial fistulas, and even a jaw defect. Consequently, sequence therapy and sometimes extensive surgery and reconstructions are needed to manage these sequelae. Treatment options may include pain medication, antibiotics, the removal of sequesters, hyperbaric oxygen therapy, segmental resection of the mandible, and free flap reconstruction. Microanastomosed free-flaps are considered to be promising choice for ORN reconstruction in recent researches, and new methods including three-dimensional (3-D) printing, pentoxifylline, and amifostine are used nowadays in trying increase the success rates and improve quality of the reconstruction. This review summarizes the main research progress in osteoradionecrosis and reconstruction treatment of osteoradionecrosis with mandibular defect.
PubMed: 36968640
DOI: 10.1155/2023/1440889