Amifostine protects from the peripheral sensory neuropathy induced by oxaliplatin in mice

Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.

Butirato de sodio como agente coadyuvante de la acción radioprotectora de la amifostina / Sodium butyrate as a coadyuvant agent of the radioprotecting action of amifostine / Butirato de sódio como agente coadjuvante da ação radioprotetora da amifostina

Entre los escasos radioprotectores en uso, la amifostina resulta eficaz para reducir la toxicidad aguda inducida por la radiación ionizante. Sin embargo, presenta efectos tóxicos importantes que impiden su uso repetido o en dosis altas. Es necesario entonces desarrollar radioprotectores menos tóxicos, por sí mismos o como coadyuvantes de la amifostina en dosis bajas. Se expusieron ratas Sprague-Dawley a una dosis de rayos X de 6 Gy (cuerpo entero). Se ensayó el butirato de sodio como mitigante luego de una dosis baja de amifostina previa a la irradiación. A distintos tiempos después de la irradiación se realizó el recuento de eritrocitos, leucocitos y la fórmula leucocitaria. Los efectos genotóxicos se evaluaron en leucocitos de sangre mediante el ensayo Cometa. Se realizaron también estudios de supervivencia a 60 días y la evaluación histológica del duodeno e intestino grueso. El efecto del tratamiento resultó moderadamente protector respecto de la recuperación de los valores normales de eritrocitos, leucocitos y la fórmula leucocitaria en los animales sobrevivientes en ambos sexos, así como de los epitelios intestinales y el ADN de los leucocitos. También aumentó significativamente la sobrevida a 60 días. La radioprotección con amifostina en una dosis baja seguida de una mitigación con butirato fue claramente significativa.

Among the few radioprotectors in use, amifostine is effective in reducing the acute toxicity induced by ionizing radiation. However, it has important toxic effects that prevent its repeated use or in high doses. It is necessary then to develop less toxic radioprotectors, by themselves or as adjuvants of amifostine in low doses. Sprague-Dawley rats were exposed to an X-ray dose of 6 Gy (whole body). Sodium butyrate was tested as a mitigant after a low dose of amifostine prior to irradiation. At different times after the irradiation, the erythrocytes, leukocytes and the leukocyte formula were counted. Genotoxic effects were evaluated in blood leukocytes by the Comet assay. Sixty-day survival studies and histological evaluation of the duodenum and large intestine were also performed. The effect of the treatment was moderately protective with respect to the recovery of the normal values of erythrocytes, leukocytes and the leukocyte formula in the surviving animals in both sexes as well as for the intestinal epithelia and leukocytes DNA. It also significantly increased the 60-day survival. The radioprotection with amifostine in a low dose followed by mitigation with butyrate was clearly significant.

Entre os poucos radioprotetores em uso, a amifostina é eficaz na redução da toxicidade aguda induzida pela radiação ionizante. No entanto, tem importantes efeitos tóxicos que impedem seu uso repetido ou em altas doses. É necessário, então, desenvolver radioprotetores menos tóxicos, isoladamente ou como coadjuvantes da amifostina em baixas doses. Ratos Sprague-Dawley foram expostos a uma dose de raios X de 6 Gy (corpo inteiro). O butirato de sódio foi testado como mitigante após uma dose baixa de amifostina antes da irradiação. Em diferentes momentos após a irradiação, os eritrócitos, leucócitos e a fórmula de leucócitos foram contados. Os efeitos genotóxicos foram avaliados em leucócitos de sangue pelo ensaio Cometa. Estudos de sobrevida de 60 dias e avaliação histológica do duodeno e do intestino grosso também foram realizados. O efeito do tratamento resultou moderadamente protetor em relação à recuperação de valores normais de eritrócitos, leucócitos e fórmula leucocitária nos animais sobreviventes em ambos os sexos, bem como protegeu epitélios intestinais e o DNA dos leucócitos. Também aumentou significativamente a sobrevida para 60 dias. A radioproteção com amifostina em baixa dose seguida de uma mitigação com butirato foi claramente significativa.

Amifostine reduces inflammation and protects against 5-fluorouracil-induced oral mucositis and hyposalivation

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.

An analysis of protective effect for mucositits by amifostine on total body irradiation during hematopoietic stem cell transplantation / 中华放射医学与防护杂志

Objective To evaluate the efficiency of amifostine in protecting against oral and gastrointestinal mucositis in hematologic malignancies patients with high-dose total body irradiation following the hematopoietic stem cell transplantation,and assess the hematologic recovery as well as the potential side effect of amifostine.Methods Thirty-two hematologic malignancies patients underwent hematopoietic stem cell transplantation in our institution from 2012 to 2016 were retrospectively analyzed.All of them were treated with total body irradiation (700-1 200 cGy) and high-dose chemotherapy,in which 14 patients received 400 mg amifostine before radiotherapy.Prior institutional experience in 18 patients treated without amifostine was used as a historical comparison (no-amifostine group).Results Severe oral mucositis occurred in 14.3％ of patients in the amifostine group while 77.2％ in the no-amifostine group (x2 =10.62,P ＜0.05).Total parenteral nutrition was used in 21.4％ of amifostine group and 38.8％ in noamifostine group (P ＞ 0.05).The rates of grade 2 and 3 gastrointestinal mucositis were 35.7％ and 61.5％ in amifostine group,while in no-amifostine group the rates were 33.3％ and 66.7％,respectively (P ＞ 0.05).No significant difference was found in engraftnent times of granulocyte and platelet.No amifostine related side effects were observed.Conclusions The combination of amifostine and total body irradiation conditioning therapy during hematologic stem cell transplantation might reduce the severity of oral mucositis.The utilize of amifostine has no obvious effect on hematopoietic recovery and can be well tolerated.

Mechanism of amifostine combined with low dose cyclosporine in refractory immune thrombocytopenia / 中国生化药物杂志

Objective To explore the effect of amifostine combined with low-dose cyclosporine in treatment of refractory immune thrombocytopenia effect and related mechanisms.Methods 60 cases of refractory immune thrombocytopenia patients using parallel randomized controlled groups, divided into three groups, 20 cases in each group, amifostine group were treated with amifostine, cyclosporine group were treated with cyclosporine, amifostine+CSA group received amifostine+cyclosporine A treatment.The platelet count, platelet membrane glycoprotein antibody, lymphocyte subsets and bone marrow megakaryocyte count were observed and compared.Results After different treatment of three, six months, the level of platelet count of patients in three groups were compared with the group before treatment were significantly increased, and the treatment of platelet count level of amifostine group and cyclosporine group were significantly lower than that of amifostine +CSA group, the difference was statistically significant (P<0.05), there was no significant difference between amifostine group and cyclosporine group.The total efficacy of amifostine+CSA group was significantly higher than the other two groups, the difference was statistically significant ( P<0.05 ) , there was no significant difference between amifostine group and cyclosporine group.After the treatment, the platelet membrane glycoprotein GPIIb/IIIa antibody levels in three groups were significantly increased, and ring the detection level of amifostine+CSA group after treatment was significantly higher than the other two groups, the difference was statistically significant (P<0.05), there was no significant difference between amifostine group and cyclosporine group.After treatment, the three groups of CD4 +, CD4 +/CD25 +and CD4 +/CD8 +levels were significantly increased, CD8 +decreased significantly, the difference was statistically significant (P<0.05).And the level of change after treatment with amifostine +cyclosporine group was significantly higher than that of the other two groups, the difference was statistically significant (P<0.05), there was no significant difference between amifostine group and cyclosporine group.After treatment, the number of bone marrow megakaryocytes in the three groups was significantly lower than that before treatment , the level of count after treatment with amifostine +cyclosporine was significantly lower than that of the other two groups, the difference was statistically significant (P<0.05).there was no significant difference between amifostine group and cyclosporine group.The adverse reactions of amifostine group and amifostine+CSA group were significantly lower than that in cyclosporine group, the difference was statistically significant (P<0.05).there was no significant difference between amifostine group and amifostine+CSA group.Conclusion Amifostine combined with low dose of cyclosporine in treatment of refractory immune thrombocytopenia can play a synergistic effect, improve the therapeutic effect, and effectively reduce the dosage and adverse reactions.

Efecto radioprotector del piruvato de etilo, solo o como coadyuvante de la amifostina / Radioprotective effect of ethyl pyruvate alone or as a coadyuvant of amifostine / Efeito radioprotetor do piruvato de etila, sozinho ou como um coadjuvante de amifostina

Entre los radioprotectores con uso clínico se destaca la amifostina (WR- 2721), eficaz pero con efectos secundarios que impiden su uso repetitivo. Es interés de los autores desarrollar radioprotectores menos tóxicos, por sí mismos o como coadyuvantes de amifostina. Ratas machos o hembras se expusieron a una dosis de rayos X de 2 Gy. Se ensayó el piruvato de etilo, solo o conjuntamente con amifostina. Cuarenta y ocho horas después de la exposición a la radiación, se realizó el recuento de eritrocitos, de leucocitos y la fórmula leucocitaria. Los efectos genotóxicos se evaluaron en leucocitos de sangre mediante el ensayo Cometa. Se realizaron también estudios de supervivencia a 60 días post-irradiación. En los animales irradiados disminuyeron los eritrocitos, y el recuento de leucocitos se redujo drásticamente respecto al control, presentando además una fórmula alterada. El tratamiento con piruvato de etilo resultó en una protección de los eritrocitos en ambos sexos. El daño genético disminuyó significativamente por el tratamiento con piruvato de etilo solo o combinado con amifostina, y en hembras se observó una mayor supervivencia solo con el tratamiento combinado. El piruvato de etilo mostró una acción radioprotectora significativa, que podría mejorarse aumentando la dosis o el tiempo de tratamiento, ya que tiene muy baja toxicidad.

Among the currently available radioprotectors, only amifostine (WR-2721) has shown in clinical trials to reduce radiation-induced toxicity. This compound is an efficient radioprotector but it exhibits some undesirable side effects which prevent its repetitive use. Efforts are directed to develop radioprotective agents with lower toxicity, with their own protective potential or suitable as coadyuvants of amifostine. The present study describes the results obtained by repetitive oral administration of ethyl pyruvate. Male or female rats were exposed to an X-ray dose of 2 Gy. Forty-eight hours after exposure to radiation, erythrocyte count, leukocyte and differential count were performed. Genotoxic effects were assessed in blood leukocytes by the Comet assay. Survival studies were also performed at 60 days post-irradiation. Eritrocyte and leukocyte were reduced in animals exposed to radiation compared to the control, also presenting an altered formula. Treatment with ethyl pyruvate resulted in a protection on erythrocytes of both sexes. Genetic damage was significantly decreased by ethyl pyruvate alone or combined with amifostine, and in females, higher survival was observed only with combined administration. Ethyl pyruvate showed a significant radioprotective action, which could be improved by increasing the dose or time of treatment because it has low toxicity.

Entre os radioprotetores com uso clínico destaca-se a amifostina (WR-2721) eficaz mas com efeitos secundários que impedem seu uso repetitivo. O interesse dos autores é desenvolver radioprotetores menos tóxicos, por si mesmos ou como coadjuvantes de amistofina. Ratos machos ou fêmeas foram expostos a doses de raios X de 2Gy. Ensaiou-se o piruvato de etila, só ou junto com amifostina. Quarenta e oito horas após a exposição à radiação foi realizada a contagem de eritrócitos, de leucócitos e da fórmula leucocitária. Efeitos genotóxicos foram avaliados em leucócitos do sangue pelo Ensaio Cometa. Estudos de sobrevivência foram também realizados a 60 dias pós-irradiação. Nos animais irradiados diminuíram os eritrócitos, e a contagem de leucócitos se reduziu drasticamente em comparação com o controle, apresentando também uma fórmula alterada. O tratamento com piruvato de etila resultou numa proteção dos eritrócitos em ambos os sexos. O dano genético diminuiu significativamente pelo tratamento com piruvato de etila sozinho ou combinado com amifostina, e nas fêmeas se observou maior sobrevivência só com o tratamento combinado. O piruvato de etila mostrou uma ação radioprotetora significativa, que poderia ser melhorada pelo aumento da dose ou do tempo de tratamento, visto que tem baixa toxicidade.

The effect of amifostine on bacterial translocation after radiation induced acute enteritis

ABSTRACT PURPOSE: To investigate the effects of amifostine on bacterial translocation and overgrowth in colonic flora after acute radiation enteritis in a rat model. METHODS: Thirty-two female Wistar albino rats were divided into four groups: Group-1 (n=8): only normal saline was administered intraperitoneally. Group-2 (n=8): first serum saline was administered intraperitoneally and 30 minutes later 20 Gy radiation was applied to abdominopelvic region. Group-3 (n=8): only amifostine 200 ml/kg was administered intraperitoneally and radiation was not applied. Group-4 (n=8): first amifostine 200 ml/kg was administered intraperitoneally and 30 minutes later 20 Gy radiation was applied to abdominopelvic region. On the 5th day after radiation, samples of mesenteric lymph tissues and cecal contents were taken by laparotomy for microbiological culture. RESULTS: Intraperitoneal amifostine administration significantly decreased the bacterial overgrowth related to radiation in colon but did not significantly decrease the bacterial translocation. CONCLUSİON: Although not providing a full protection on the damaged mucosal barrier, amifostine significantly decreased the bacterial overgrowth in the cecal content after high dose radiation. There is a need to find out appropriate amifostine dose under different radiation applications avoiding bacterial translocation in gastrointestinal system.

Effects of amifostine on formation of abdominal aortic aneurysm in mice induced by benzo[ a] pyrene / 中国病理生理杂志

AIM:To study the role of amifostine on the formation of benzo [a]pyrene (BaP)-induced abdomi-nal aortic aneurysm ( AAA) in C57BL/6J mice and the underlying mechanism .METHODS: RAW246.7 mononuclear macrophage in vitro were divided into control group , DMSO group, BaP group, low dose (1 μmol/L) amfostine treated group, middle dose (5 μmol/L) amfostine treated group and high dose (25μmol/L) amfostine treated group .The influ-ence of BaP on the expression of matrix metalloproteinase (MMP)-9, MMP-12, TNF-α, NF-κB in the RAW246.7 mono-nuclear macrophages in vitro was determined by Western blot .Male C57BL/6J mice (8 months old) were divided into con-trol group, model group (AngII+BaP group), low dose (50 mg/kg) amfostine treated group and high dose (100 mg/kg) amfostine treated group.After 6 weeks, the abdominal aorta were isolated .The aortic tissues were subjected to HE and Masson staining.The vascular wall structure , infiltration of macrophage , the expression of MMP-9, MMP-12, TNF-α, NF-κB were evaluated by Western blot and immunochemistry staining .RESULTS:Amifostine attenuated BaP-induced expres-sion of TNF-α, MMP-9, MMP-12, NF-κB in the RAW246.7 mononuclear macrophages (P<0.05).The results of animal experiments showed that the incidence of AAA in high dose amifostine treated group were significantly lower than that in low dose amifostine treated group and model group (P<0.05).Immunohistochemistry staining observation showed that amifos-tine inhibited the aortic macrophage infiltration more obviously in high amifostine treated group compared with model group and low dose amifostine treated group (P<0.05).Compared with model group and low dose amifostine treated group , the MMP-9, MMP-12, TNF-αand NF-κB expression of abdominal aorta in high amifostine treated group was reduced signifi -cantly ( P<0.05 ) .CONCLUSION: Amifostine inhibits BaP-induced activation of macrophages , and also prevents the formation of abdominal aortic aneurysm in C 57BL/6J mice induced by BaP by inhibition of the NF-κB pathway, macro-phage infiltration and the expression of TNF-αand MMPs.

Effect of amifostine on proliferation and differentiation of human megakaryocyte Dami cells / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of amifostine(Amf)on the differentiation of human megakaryocyte cell line-Dami. METHODS Dami cells were treated with Amf 0.01-5.0 mmol · L-1 for 12 d. Dami cells were counted every day for the growth curve:only cells with a diameter>20μm. The platelet demarcation membrane system was observed by transmission electron microscopy. The expression of CD33,CD34,CD41a and DNA ploidy was detected by flow cytometry. RESULTS Amf 0.1-1.0 mmol · L-1 promoted the differentiation of Dami cells ,but inhibited their proliferation at a concentration>1.0 mmol · L-1. When these cells were treated with Amf 1.0 mmol · L-1 for 12 d,the platelet demarcation membrane system was observed,the percentage of cells with a diameter >20 μm was increased by 24.6%(P1.0 mmol·L-1).

Advances in antiradiation drugs / 军事医学

Antiradiation drugs, also known as radioprotective agents, can prevent humans from radiation injury,reduce the clinical symptoms of radiation sickness,promote early recovery and reduce morbidity or mortality.Early developments of such agents focused on thiol synthetic compounds, such as amifostine (WR 2721).This compound reduced mortality, but its disadvantages, such as large use and high toxicity, limited its use in clinical practice.To find a suitable radioprotective agent is crucial to reducing side effects induced by ionizing radiation and increasing survival rate in patients during radiotherapy.In this paper, the classification and mechanism of radioprotective agents are reviewed and future developments in this field are predicted.

Amifostine Reduces Radiation-induced Pneumonitis in Patients with Non-small Cell Lung Cancer:A Meta-analysis / 华中科技大学学报(医学版)

Objective To evaluate the efficacy of amifostine in diminishing the incidence of radiation‐induced pneumonitis in patients with non‐small cell lung cancer (NSCLC)by using the meta‐analysis.Methods Medline ,Embase ,Cenfang ,CNKI , CBM ,Wanfang ,ASCO ,and ESMO databases were searched for randomized controlled trials(RCTs)on use of amifostine during radiotherapy for NSCLC and the papers were published before February 2015.Meta‐analysis was used to evaluate the efficacy of amifostine in decreasing the incidence of radiation‐induced pneumonitis.Results A total of 8 RCTs were identified with 394 ca‐ses in amfostine group and 402 in control group.The pooled relative risk(RR)of developing radiation‐induced pneumonitis(grade≥3)was 0.50(95% CI:0.37 -0.69 ,Z=4.33 ,P<0.01)in amfostine group when compared with control group.Conclusion Amifostine can significantly decrease the risk of developing radiation‐induced pneumonitis in NSCLC patients treated by radio‐therapy.

Comparative study of the effects of rhKGF, CBLB502 and WR2721 on radiation-induced oral mucositis / 解放军医学杂志

Objective To compare the protective effect of rhKGF, CBLB502 and WR2721 on radiation-induced oral mucositis (ROM). Methods Fifty male 6-8-week-old C57BL/6J mice were randomly divided into normal group, irradiation control group, rhKGF group, CBLB502 group, and WR2721 group (n=10 each). The 30-day survival rate and change in body weight of mice that had received 17Gy irradiation of head and neck area were recorded. In another group of 20 mice, 1% toluidine blue staining and HE staining were used to observe oral ulcers and pathological changes in the tongue tissue. The proliferation of keratinocyte cells was assessed by Ki-67 immunohistochemistry. Results Compared with the irradiation control group, administration of rhKGF and WR2721 could significantly improve the 30-day survival rate, accelerate the recovery of body weight, and promote the proliferation of keratinized epithelial cells of mice after irradiation, without inducing obvious oral mucositis. However, There was no significant difference between CBLB502 group and irradiation control group in survival rate, body weight and pathological changes in tongue tissues of mice. Conclusion rhKGF and WR2721 could alleviate ROM and improve the survival of mice, while CBLB502 has no such effect.

Radioprotective effects of CBLB502 on γ-radiated rhesus monkey / 解放军医学杂志

Objective A Rhesus monkey model was employed to study the radioprotective effects of a Toll-like receptor 5 agonist, CBLB502, against 7.0Gy whole-body irradiation of 60Co gamma-rays. Methods Thirty animals were assigned to a placebo treatment group, a WR-2721 positive control group, and three CBLB502 treatment groups (n=6 animals/group). Each animal was irradiated with 7.0Gy 60Co γ and given CBLB502 at 2.5, 10 and 40μg/kg, respectively in treatment groups, or WR-2721 at 30mg/kg, or physiological saline 0.3ml/kg for the placebo treatment group. The treatment was given once by intramuscular injection 30 min before irradiation. All irradiated animals received symptomatic treatment based on same guidelines. General observation, peripheral blood tests, hemopoietic progenitor cell colony-counting, and histopathological examination were performed. Results We found that 10 or 40μg/kg CBLB502 treatment resulted in 100% survival, while the survival rate was 33% in placebo treatment group. Hematopoietic recovery in the WR-2721 treatment group was marginally superior to the irradiation control group. Nadirs of peripheral white cell and platelet counts of animals treated with 40μg/kg of CBLB502 were significantly higher than those of the placebo treatment group (P60Co γ-rays would suffer from severe acute radiation sickness of hematopoietic system. CBLB502 at 40μg/kg is radioprotective in this model and a single intramuscular injection of CBLB502 in a dose of 40μg/kg 30min before irradiation gives better radioprotective effects than WR-2721.

Acupoint Sticking at Shenque (CV 8) with Ginger-preparedBan Xia (Rhizoma Pinelliae) for Nausea and Vomiting Induced by Amifostine / 针灸推拿医学（英文版）

Objective: To observe the treatment effect of acupoint sticking at Shenque (CV 8) with ginger-preparedBan Xia (Rhizoma Pinelliae) on nausea and vomiting induced by Amifostine for myelodysplastic syndromes (MDS). Methods: Totally 124 eligible subjects intervened by Amifostine were randomized into 2 groups by the visiting order,an observation group and a control group,62 in each group. The control group was intervened by conventional treatment, while the observation group was by acupoint sticking at Shenque (CV 8) with ginger-preparedBan Xia (Rhizoma Pinelliae) in addition to the same conventional treatment. The occurrence rate of nausea and vomiting in the two groups were observed. Results: After intervention, the occurrence rate of nausea and vomiting in the observation group was significantly lower than that in the control group (P Conclusion: Acupoint sticking at Shenque (CV 8) with ginger-prepared Ban Xia (Rhizoma Pinelliae)can produce a content effect on nausea and vomiting induced by Amifostine for MDS.

A case-control study of therapy of amifostine plus chemotherapy on acute myeloid leukemia consolidation / 中国综合临床

Objective To investigate the protective effect of normal hematopoietic and without causing the increase of relapse rate of amifostine in patients with acute myeloid chemotherapy.Methods One hundred and forty-two acute myeloid leukemia(AML) patients were selected and divided into combination group(n =56) and chemotherapy alone group (n =86).Hematological toxicity and non-hematologic toxicity,response rate,duration of response of patients were prospective,non-randomized,case-control study.Results Fifty-six patients in combined group included 30 male and 26 female patients,and 18 patients in high risk stage and 32 patients in intermediate risk stage and 6 patients in low risk.The median age was (35.14 ± 14.42) year in combination group.Chemotherapy alone group included 58 male 28 female patients,and 14 patients in high risk and 64 patients in intermediate risk and 8 patients in low risk.The median age was (46.58 ± 16.99) year.There were no significant difference between two groups in terms of gender (P =0.318) and risk stage(P =0.262).But more young patients were in combination group compared with chemotherapy alone group and there was significant difference(P =0.004).In combination group,42.9％ (24 cases)patients got high Ara-C dose and 32.1％ (18 cases) patients got high HAA dose chemotherapy compared with control group (14.9％ (12 cases)and 20.9％ (18 cases)).The during periods of platelet with ＜20 × 109/L in combination was 0(0,7) day,lower than that in chemotherapy alone group (9 (4,14),P =0.01).Meanwhile the volume of platelet infusion in combination group was less than that in chemotherapy alone group and the nadir of platelet4(0(0,3) U vs.4(1,6) U,P =0.02).No statistic difference was found in two groups regarding of non-hematological side effects and the relapse rate (before and after treatment,combination group:96.4％ (54/56) ; Chemotherapy alone group:98.8 ％ (85/86) ; P=0.062).Conclusion Amifostine may provide protection for AML patients,can short duration of thrombocytopenia,reduce platelet transfusions,and other side effect was no significant difference.

Determination of amifostine in human saliva by HPLC-MS/MS / 中国药学杂志

OBJECTIVE: To establish an HPLC-MS/MS method (high performance liquid chromatography-tandem mass spectrometry) for the direct determination of amifostine in human saliva. METHODS: Saliva samples were collected from six adult healthy volunteers. After protein precipitation and addition of the internal standard (IS) huperzine-A (HupA), HPLC-MS/MS was used to analyze amifostine. The analysis was conducted using a ZIC-HILIC analytical column (2.1 mm × 100 mm, 3.5 μm). Electrospray ionization was used with multiple reaction monitoring (MRM) mode. RESULTS: The lower limit of quantification (LLOQ) of the method was 0.938 mg · L-1 (S/N<10). The standard curve was linear in the range of 0.938-30 mg · L (r=0.9991, n=6). The inter-day and intra-day RSDs were all less than 15% for the low, medium and high concentration quality control samples (1.0, 5.0 and 25 mg · L-1): The values of recovery were all more than 85%. CONCLUSION: The method is direct, rapid, simple and sensitive, and suitable for the determination of amifostine in saliva samples.

Seguimiento del periodo inmediato post-autotrasplante de células progenitoras hematopoyéticas / Follow-up of immediate period of post-autologous hematopoietic progenitor cells transplant

Introducción: el objetivo de este estudio fue describir el comportamiento clínico y de laboratorio presentado en autotrasplante de células progenitoras hematopoyéticas en un grupo de pacientes del Hospital Militar Central en el periodo de enero 2007 a octubre de 2010. Material y métodos: es un estudio descriptivo retrospectivo a través de la revisión de las historias clínicas de estos pacientes obteniendo la información sobre tiempo de alta pos trasplante, requerimiento transfusional, periodo aplásico (neutropenia absoluta, trombocitopenia severa, anemia severa y presentación de neutropenia febril), número de células madre trasplantadas, fuente y criopreservación o no. Los resultados de las diferentes variables por medir fueron tabulados y almacenados en una base para su posterior análisis descriptivo univariado cualitativo y cuantitativo. Resultados: todos los pacientes injertaron adecuadamente. El injerto de neutrófilos ocurrió entre 11-23 días, con una media de 14.44; el injerto de plaquetas ocurrió entre 13-25 días, con una media de 16.33, y la duración de la neutropenia absoluta fue de 5-14 días, con una media de 7.28. Conclusiones: la recuperación de los pacientes fue similar a lo descrito en la literatura internacional. (Acta Med Colomb 2012; 37: 172-176).

Introduction: the aim of this study was to describe the clinical and laboratory performance in autologous transplants of hematopoietic progenitor cells in a group of patients in the Hospital Militar Central in the period january 2007 to october 2010. Material and methods: we performed a retrospective descriptive study by reviewing the medical records of these patients in regard to the time of discharge from hospital after transplantation, transfusion requirement, aplastic period (absolute neutropenia, severe thrombocytopenia, severe anemia and febrile neutropenia presentation ), number of transplanted stem cells, source, and whether there was or not cryopreservation. The results of the different variables measured were tabulated and stored in a database for later univariate descriptive qualitative and quantitative analysis. Results: all patients grafts functioned properly. Neutrophil engraftment occurred between 11-23 days, with a mean of 14.44, platelet engraftment occurred between 13-25 days, with a mean of 16.33, and the absolute duration of neutropenia was 5-14 days, with a median of 7.28. Conclusions: the recovery of patients was similar to that described in the international literature. (Acta Med Colomb 2012; 37: 172-176).

The effects of a rotating magnetic field in the prevention and treatment of irradiation-induced esophagitis / 中华物理医学与康复杂志

Objective To observe the effect of a rotating magnetic field in preventing and treating irradiation-induced esophagitis in rats. Methods Forty female Wistar rats were randomized into 5 groups:a non-irradiated control group,an irradiation group,an amifostine treatment group ( amifostine group ),a 90 min magnetic field treatment group (90 min magnetic group) and a 120 min magnetic field treatment group ( 120 min magnetic group),with 8 rats in each group.The esophaguses of all rats except those in the control group were exposed to a single irradiation with 6 MV X-rays from a linear accelerator at a dosage of 43 Gy.Four rats in each group were randomly chosen to be observed 1 and 2 weeks after the irradiation.Blood cytokines were detected in their arterial blood.Any pathological changes of the esophagus were observed with HE staining under a light microscope at the same time. Results Irradiation-induced esophagitis was observed in the irradiation group 7 days after irradiation,with obvious exfoliation and necrosis of the esophagal epithelium mucosae.The submucosa were hyperaemic and dropsical with abundant inflammatory cell infiltration.The pathological changes of the esophagus were similar at 7 and 14 days after irradiation.However,the irradiation-induced esophagitis of rats in the amifostine group,the 90 min magnetic group and the 120 min magnetic group were relatively slighter and the blood leucocytes and neutrophis in those 3 groups were significantly lower than those in the irradiation group,while a tendency toward repair of the mucosa of the esophagus was detected.Serum TNF-α,IL-1 and IL-6 in the 90 min magnetic group and 120 min magnetic group were significantly lower than those in the irradiation group. Conclusions Both a rotating magnetic field and amifostine can help prevent and treat irradiation-induced esophagitis.Their therapeutic efficacy is similar.Exposure to a rotating magnetic field could inhibit the expression of inflammatory factors,and thus lessen the inflammatory reaction of acute irradiation-induced esophagitis.

Prophylactic efficacy of combination of DRDE-07 and its analogues with amifostine against sulphur mustard induced systemic toxicity.

Sulphur mustard, [bis (2-chloroethyl)] sulphide (SM), is a bifunctional alkylating agent. SM forms sulphonium ion in the body which alkylates DNA and several other macromolecules, and induces oxidative stress. Although several antidotes have been screened for the treatment of systemic toxicity of SM in experimental animals none of them are recommended so far. In the search for more effective and less toxic antidotes, various combinations were tried against SM induced toxicity and skin lesions. SM exposed through percutaneous route was used to evaluate the prophylactic efficacy of various combinations. Low dose of DRDE-07 (S-2(2-aminoethylamino) ethyl phenyl sulphide), DRDE-30 [S-2(2-aminoethyl amino) ethyl propyl sulphide], DRDE-35 [S-2(2-aminoethyl amino) ethyl butyl sulphide] with amifostine combinations, were given orally 30 min prior to SM exposure. Significant depletion was observed in body weight, organ body weight index and hepatic GSH and GSSG content in mice after SM exposure. Pretreatment with low dose of different combinations of DRDE-07, DRDE-30 and DRDE-35 with amifostine could recover biochemical alterations and histopathological changes caused by SM exposures.

Amifostine ameliorates recognition memory defect in acute radiation syndrome caused by relatively low-dose of gamma radiation

This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis.