RESUMEN
Arsenic trioxide (ATO)-based regimens are standard in acute promyelocytic leukemia (APL). ATO-related nephrotoxicity has not been reported. We reviewed APL patients treated with ATO to identify cases of acute kidney injury (AKI). Clinically significant cases were characterized. Multivariate analysis was performed to identify predictors of idiopathic, clinically significant AKI. One hundred and eight patients were included. ATO dose was 0.15 mg/kg/day using actual body weight with no dose cap. Thirty-one (28.7%) AKI cases were identified, 10 (32.3%) clinically significant. Six were idiopathic; five required dialysis. The proportion with significant, idiopathic AKI was 15.8% in patients receiving >15mg ATO versus 0% in those receiving ≤15mg (p = 0.001). On multivariate analysis, only ATO dose was a significant predictor of clinically significant AKI (odds ratio of 1.91, 95%CI, 1.19-3.07, p = 0.007). High-dose ATO may be associated with significant nephrotoxicity. We recommend that ATO dose be capped at 15 mg to minimize toxicity for this curable disease.
Asunto(s)
Lesión Renal Aguda , Arsenicales , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Leucemia Promielocítica Aguda , Humanos , Trióxido de Arsénico/efectos adversos , Leucemia Promielocítica Aguda/complicaciones , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Tretinoina/efectos adversos , Obesidad/complicaciones , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Arsenicales/efectos adversos , Óxidos/efectos adversosRESUMEN
Arsenical medicine has obtained its status in traditional Chinese medicine for more than 2,000 years. In the 1970s, arsenic trioxide was identified to have high efficacy and potency for the treatment of acute promyelocytic leukemia, which promoted many studies on the therapeutic effects of arsenic trioxide. Currently, arsenic trioxide is widely used to treat acute promyelocytic leukemia and various solid tumors through various mechanisms of action in clinical practice; however, it is accompanied by a series of adverse reactions, especially cardiac toxicity. This review presents a comprehensive overview of arsenic trioxide from preclinical and clinical efficacy, potential mechanisms of action, toxicities, and rescue strategies for toxicities to provide guidance or assistance for the clinical application of arsenic trioxide.
Asunto(s)
Antineoplásicos , Arsenicales , Leucemia Promielocítica Aguda , Neoplasias , Humanos , Trióxido de Arsénico/efectos adversos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/inducido químicamente , Óxidos/efectos adversos , Arsenicales/efectos adversos , Neoplasias/tratamiento farmacológico , Antineoplásicos/efectos adversosRESUMEN
Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.
Asunto(s)
Arsénico , Leucemia Promielocítica Aguda , Niño , Humanos , Arsénico/efectos adversos , Trióxido de Arsénico/efectos adversos , Arsenicales/efectos adversos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Resultado del Tratamiento , Tretinoina/uso terapéuticoRESUMEN
BACKGROUND: Arsenic trioxide (ATO) might be effective for myelodysplastic syndrome (MDS) by apoptosis induction and demethylation. But ATO has not been widely recommended for small sample and conflicting conclusion of existing trials. This review aimed to systematically evaluate the efficacy of regimens containing ATO for the MDS and explore optimal combination. METHOD: Randomized clinical trials (RCTs) about ATO regimens were retrieved from China National Knowledge Infrastructure, Embase and PubMed. With odds ratio (OR) as the effect size, network meta-analysis (NMA) and component network meta-analysis (CNMA) were conducted by R and 'netmeta' package, after study selection, quality assessment and data extraction. RESULT: Thirty-night RCTs were included with a total of 2125 patients, including 1235 treated by ATO containing regimen. With support therapy alone as reference, no inconsistency and heterogeneity were observed. Although NMA did not demonstrate better efficacy of ATO alone, the result of CNMA indicated that ATO was effective in the improvement of overall remission (ORR) [OR = 2.09(1.61, 2.71)] and complete remission (CR) [OR = 1.66(1.25, 2.21)]. Five ATO-containing regimens reported could effectively improve ORR, some of them benefit in CR or hematological improvement (HI) as well. ATO + Traditional Chinese Medicine (TCM), ATO + Thalidomide (T)+TCM, ATO + Chemotherapy (Chem)+T + TCM were regarded as the optimal combination, which improved both ORR, CR and HI in theory. ATO did not increase the risk of common adverse events compared to supportive therapy [(OR = 0.90(0.67, 1.21)]. CONCLUSION: ATO may be an effective and well-tolerant option for patients with myelodysplastic syndrome.
Asunto(s)
Arsenicales , Síndromes Mielodisplásicos , Humanos , Trióxido de Arsénico/efectos adversos , Metaanálisis en Red , Arsenicales/efectos adversos , Óxidos/efectos adversos , Síndromes Mielodisplásicos/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Realgar-Indigo naturalis formula (RIF) is a traditional Chinese medicine containing As4S4 and effective in treating acute promyelocytic leukemia (APL). The dose of RIF remains to be determined in pediatric patients. Comparison of plasma arsenic concentrations and toxicity between RIF and arsenic trioxide (ATO) treatment in APL may help to establish an appropriate therapeutic dose of RIF for children. From October 2018 to March 2020, 19 pediatric patients with APL treated with SCCLG-APL protocol were included, 9 in RIF group at 135 mg/kg/day orally three times daily, and 10 in ATO group at 0.16 mg/kg/day intravenously over 12 h daily. Peak and trough plasma arsenic concentrations were assayed at D1, 2, 7 and 14 of induction treatment. Urine arsenic excretions were assessed with spot urine samples and the measurements were adjusted using creatinine. Toxicities were compared between two groups. The plasma arsenic concentration reached steady state at D7 either in the RIF or ATO group, and the mean peak and trough concentrations were similar between two groups (P > 0.05), which were 0.54 µmol/L and 0.48 µmol/L in RIF group, and 0.63 µmol/L and 0.51 µmol/L in ATO group, respectively. Urine arsenic excretion rate was positively correlated with the concentration of plasma arsenic. The rates of treatment-related adverse events were similar in two groups. In conclusion, the dose of RIF at 135 mg/kg/day may be an appropriate therapeutic dose in children with APL. Urine arsenic level can be used as an indicator to estimate plasma arsenic concentration. Trial registration www.clinicaltrials.gov NCT02200978.
Asunto(s)
Antineoplásicos , Arsénico , Arsenicales , Leucemia Promielocítica Aguda , Antineoplásicos/uso terapéutico , Trióxido de Arsénico/efectos adversos , Arsenicales/efectos adversos , Niño , Medicamentos Herbarios Chinos , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Tretinoina/uso terapéuticoRESUMEN
Qinghuang Powder (QHP), an oral arsenic, has become an effective drug in the treatment of myelodysplastic syndromes (MDS) in Xiyuan Hospital, China Academy of Chinese Medical Sciences for many years, and the action mechanism of the compound or active ingredient As2S2 of QHP has been elucidated. Considering the relatively safety, chemotherapy-free and convenient oral profile, QHP is widely used in the clinical treatment for MDS patients, especially for elderly patients. In this review, the authors document the efficacy and safety of oral arsenic-containing compound QHP in the treatment of MDS, with a special focus on the association of efficacy of QHP with the cytogenetics, prognostic risk, DNA methylation, gene mutation, blood arsenic concentration, mechanism of action of As2S2 and the countermeasures against adverse reactions of gastrointestinal tract.
Asunto(s)
Arsénico , Arsenicales , Síndromes Mielodisplásicos , Anciano , Arsénico/uso terapéutico , Arsenicales/efectos adversos , Medicamentos Herbarios Chinos , Humanos , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Polvos/uso terapéuticoRESUMEN
Arsenic trioxide (ATO) is the backbone of acute promyelocytic leukemia (APL) treatment and is dosed based on weight with no upper limit, therefore obese patients receive large doses and may be vulnerable to adverse effects and dose holdings. Twenty-seven patients receiving ATO during induction were categorized as obese (N = 16) or non-obese (N = 11) based on body mass index (BMI) ≥30 kg/m2 in this retrospective study. Doses were held or modified due to composite adverse effects in 9 (56%) obese patients and 7 (64%) non-obese patients (p = 1.00). There were higher rates of dose holdings (13% versus 0%; p = .5) and dose modifications (13% versus 0%; p = .5) due to hepatotoxicity in obese versus non-obese patients. There were no differences in efficacy parameters. These data suggest that obese patients have similar overall incidence of adverse effects to ATO as non-obese patients; any difference in risk of hepatotoxicity will require clarification in a larger study.
Asunto(s)
Arsenicales , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Leucemia Promielocítica Aguda , Protocolos de Quimioterapia Combinada Antineoplásica , Trióxido de Arsénico/uso terapéutico , Arsenicales/efectos adversos , Humanos , Leucemia Promielocítica Aguda/complicaciones , Leucemia Promielocítica Aguda/tratamiento farmacológico , Obesidad/complicaciones , Óxidos/efectos adversos , Estudios Retrospectivos , Tretinoina/uso terapéuticoRESUMEN
A 55-year-old woman developed acute promyelocytic leukaemia during treatment with all-trans-retinoic acid and arsenic trioxide. Initially, she presented with symptoms of epigastric pain, vomiting, and nausea, and she developed acute pancreatitis. She was treated with parenteral nutritional supplementation for 20 days. However, the patient continued to develop refractory hyponatraemia, hypotension, and apathy. Finally, the patient was diagnosed with Wernicke encephalopathy (WE) using head magnetic resonance imaging. The patient underwent high-dose intravenous thiamine administration, and her symptoms were alleviated. WE is a rare adverse event during acute pancreatitis therapy. Acute pancreatitis that is caused by all-trans-retinoic acid and arsenic trioxide is a rare complication of acute promyelocytic leukaemia during chemotherapy. Further study is essential to improve our comprehension of the risk factors for complications in patients with acute promyelocytic leukaemia, considering that the associated complications were potentially caused by multiple etiological factors. A better understanding of these risk factors may help to improve the prognosis of patients with acute promyelocytic leukaemia at an early stage.
Asunto(s)
Arsenicales , Leucemia Promielocítica Aguda , Pancreatitis , Encefalopatía de Wernicke , Enfermedad Aguda , Trióxido de Arsénico , Arsenicales/efectos adversos , Femenino , Humanos , Leucemia Promielocítica Aguda/complicaciones , Leucemia Promielocítica Aguda/tratamiento farmacológico , Persona de Mediana Edad , Óxidos/efectos adversos , Pancreatitis/inducido químicamente , Tretinoina/efectos adversosRESUMEN
Arsenic (As) is widely used in the modern industry, especially in the production of pesticides, herbicides, wood preservatives, and semiconductors. The sources of As such as contaminated water, air, soil, but also food, can cause serious human diseases. The complex mechanism of As toxicity in the human body is associated with the generation of free radicals and the induction of oxidative damage in the cell. One effective strategy in reducing the toxic effects of As is the usage of chelating agents, which provide the formation of inert chelator-metal complexes with their further excretion from the body. This review discusses different aspects of the use of metal chelators, alone or in combination, in the treatment of As poisoning. Consideration is given to the therapeutic effect of thiol chelators such as meso-2,3-dimercaptosuccinic acid, sodium 2,3-dimercapto-1-propanesulfonate, 2,3-dimercaptopropanol, penicillamine, ethylenediaminetetraacetic acid, and other recent agents against As toxicity. The review also considers the possible role of flavonoids, trace elements, and herbal drugs as promising natural chelating and detoxifying agents.
Asunto(s)
Antídotos/uso terapéutico , Intoxicación por Arsénico/tratamiento farmacológico , Arsenicales/efectos adversos , Quelantes/uso terapéutico , Contaminantes Ambientales/efectos adversos , Preparaciones de Plantas/uso terapéutico , Animales , Antídotos/efectos adversos , Intoxicación por Arsénico/etiología , Intoxicación por Arsénico/metabolismo , Arsenicales/metabolismo , Quelantes/efectos adversos , Exposición a Riesgos Ambientales , Contaminantes Ambientales/metabolismo , Humanos , Preparaciones de Plantas/efectos adversos , Medición de Riesgo , Resultado del TratamientoRESUMEN
Glycyrrhetinic acid (GA) is the bioactive ingredient in Glycyrrhizae Radix et Rhizoma. Our previous study has reported that GA has protective effect on realgar-induced hepatotoxicity. However, the details of the hepatoprotective mechanisms of GA on realgar-induced liver injury remain to be elucidated. In the study, mice were divided into control, GA-control, realgar, and co-treated groups. Their liver tissues were used for metabonomics study by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method. The results illustrate that GA significantly ameliorate the liver injury and metabolic perturbations caused by realgar. Some metabolites, such as phenylalanine, pyroglutamic acid (PGA), proline, carnitine, nicotinamide, choline, lysophosphatidylcholine (LPC) 16 : 0 and LPC 18 : 2 were found responsible for the hepatoprotective effect of GA. These metabolites are associated with the methylation metabolism of arsenic, cell membrane structure, energy metabolism and oxidative stress. From the results of this study, we infer that the potential hepatoprotective mechanism of GA on realgar-induced liver injury may be associated with reducing arsenic accumulation and its methylation metabolism in the liver, promoting the conjugation of arsenic and GSH to play detoxification effect, and ameliorating the liver metabolic perturbations caused by realgar.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Ácido Glicirretínico/farmacología , Metabolómica , Animales , Arsenicales/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Cromatografía Líquida de Alta Presión , Ácido Glicirretínico/química , Masculino , Espectrometría de Masas , Ratones , Sulfuros/efectos adversosRESUMEN
OBJECTIVE: To investigate the relation of blood arsenic concentration (BAC) with clinical effect and safety of arsenic-containing Qinghuang Powder (, QHP) in patients with myelodysplastic syndrome (MDS). METHODS: Totally 163 patients with MDS were orally treated with QHP for 2 courses of treatment, 3 months as 1 course. The BACs of patients were detected by atomic fluorescence spectrophotometry at 1, 3, and 6 months during the treatment, and the effective rate, hematological improvement and safety in patients after treatment with QHP were analyzed. RESULTS: After 2 courses of treatment, the total effective rate was 89.6% (146/163), with 31.3% (51/163) of hematological improvement and 58.3% (95/163) of stable disease. The hemoglobin increased from 73.48 ± 19.30 g/L to 80.39 ± 26.56 g/L (P<0.05), the absolute neutrophil count increased from 0.81 ± 0.48 × 109/L to 1.08 ± 0.62 × 109/L (P<0.05), and no significant changes were observed in platelet counts (P>0.05). Among 46 patients previously depended on blood transfusion, 28.3% (13/46) completely got rid of blood transfusion and 21.7% (10/46) reduced the volume of blood transfusion by more than 50% after treatment. The BACs were significantly increased in patients treated for 1 month with 32.17 ± 18.04 µ g/L (P<0.05), 3 months with 33.56 ± 15.28 µ g/L (P<0.05), and 6 months with 36.78 ± 11.92 µ g/L (P<0.05), respectively, as compared with those before treatment (4.08 ± 2.11 µ g/L). There were no significant differences of BACs among the patients treated for 1, 3 and 6 months (P>0.05). The adverse reactions of digestive tract during the treatment were mild abdominal pain and diarrhea in 14 cases (8.6%), and no patients discontinued the treatment. The BACs of patients with gastrointestinal adverse reactions were significantly lower than those without gastrointestinal adverse reactions (22.39 ± 10.38 vs. 37.89 ± 11.84, µ g/L, P<0.05). The BACs of patients with clinical effect were significantly higher than those failed to treatment (40.41 ± 11.69 vs. 23.84 ± 12.03, µ g/L, P<0.05). CONCLUSION: QHP was effective and safe in the treatment of patients with MDS and the effect was associated with BACs of patients.
Asunto(s)
Arsénico/sangre , Arsenicales/efectos adversos , Arsenicales/uso terapéutico , Medicamentos Herbarios Chinos/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/tratamiento farmacológico , Recuento de Células Sanguíneas , Transfusión Sanguínea , Humanos , Cariotipo , Polvos , Factores de RiesgoRESUMEN
Arsenic is a toxicant that has no dose threshold below which exposures are not harmful. Here I report a curious association of chronic homeopathic arsenic ingestion with nonspecific symptoms in a Swiss teenager. For about 4 years she had taken globules of a freely purchasable homeopathic remedy containing inorganic arsenic (iAs), infinitesimally diluted to D6 (average arsenic content per single globule: 0.85 ± 0.08 ng). In the previous 7 months she had taken 20 to 50 globules daily (average 30 ng arsenic daily). She complained of nausea, stomach and abdominal cramps, diarrhoea and flatulence, headache, dizziness, anxiety, difficulty concentrating, insomnia, snoring, leg cramps and fatigue, loss of appetite, increased thirst and sweating, reduced diuresis, weight gain, paleness and coolness of both hands with a furry feeling of the hands, eczema of the hands, arms and legs, conjunctivitis and irregular menstruation. The physical and laboratory examinations showed a body mass index of 30 kg/m2, acne vulgaris, bilateral spotted leukonychia, eczema of hands, arms and legs, non-pitting oedema of the legs, elevated plasma alkaline phosphatase activity, folate deficiency and severe vitamin D3 insufficiency. The arsenic concentration in her blood was <0.013 µmol/l, and arsenic was undetectable in her scalp hair. The total iAs concentration was 116 nmol/l in the morning urine and 47 nmol/l in the afternoon urine. The urinary arsenic concentration decreased and the patient’s complaints improved upon interruption of the arsenic globules, vitamin D3, thiamine and folic acid supplementation, and symptomatic therapy. It is concluded that an avoidable toxicant such as inorganic arsenic, for which no scientific safe dose threshold exists, should be avoided and not be found in over-the-counter medications.
Asunto(s)
Intoxicación por Arsénico/etiología , Arsenicales/efectos adversos , Fármacos Gastrointestinales/efectos adversos , Homeopatía/efectos adversos , Adolescente , Femenino , Fármacos Gastrointestinales/química , HumanosRESUMEN
OBJECTIVE: We aimed to compare the kinetics of white blood cell (WBC) and explore predictive factors of leukocytosis in non-high-risk acute promyelocytic leukemia (APL), with oral arsenic plus all-trans retinoic acid (ATRA) or intravenous arsenic trioxide (ATO) plus ATRA as a first-line treatment. METHODS: The absolute count, doubling time and peak time of WBC were analyzed in 64 newly diagnosed non-high-risk APL patients who were treated with different induction regimens containing either oral Realgar-indigo naturalis formula (RIF) (n=35) or ATO (n=29). The end points were the dynamic changes of the WBC counts during induction. The time points started at day 1 and were selected over 3-day intervals for 28days. RESULTS: Among the 64 included patients, the median initial and peak WBC counts were 1.78×109/L (range 0.31-9.89) and 12.16×109/L (range 1.56-80.01), respectively. The incidence of differentiation syndrome was 9.38%. The dynamic changes in leukocytosis showed a single peak wave in all the patients, and the median time to peak was 10 (range 2-26) days. A higher WBC count was observed in the RIF group than in the ATO group after 10days of treatment (9.22×109/L vs. 4.10×109/L, p=0.015). Patients with the peak WBC count >10×109/L had a shorter WBC doubling time compared to patients with a lower peak WBC (RIF group 4days vs. 7days, p=0.001; ATO group 4.5days vs. 23days, p=0.002). Univariate and multivariable analyses showed that the doubling time of WBC is an independent factor for the peak WBC count. CONCLUSION: Different kinetics of WBC proliferation were observed during induction with oral arsenic plus ATRA and ATO plus ATRA. The doubling time of WBC is an important independent factor for predicting the peak WBC count.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Arsenicales/efectos adversos , Medicamentos Herbarios Chinos/efectos adversos , Leucemia Promielocítica Aguda/sangre , Leucocitos/efectos de los fármacos , Leucocitosis/inducido químicamente , Óxidos/efectos adversos , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trióxido de Arsénico , Arsenicales/administración & dosificación , Medicamentos Herbarios Chinos/administración & dosificación , Femenino , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Óxidos/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Tretinoina/administración & dosificación , Adulto JovenRESUMEN
Baby foods, from the Spanish market and prepared from meat, fish, vegetables, cereals, legumes, and fruits, were analyzed to obtain the concentration of antimony (Sb), arsenic (As), bismuth (Bi), and tellurium (Te) as toxic elements and selenium (Se) as essential element. An analytical procedure was employed based on atomic fluorescence spectroscopy which allowed to obtain accurate data at low levels of concentration. Values of 14 commercial samples, expressed in nanograms per gram fresh weight, ranged for Sb 0.66-6.9, As 4.5-242, Te 1.35-2.94, Bi 2.18-4.79, and Se 5.4-109. Additionally, speciation studies were performed based on data from a non-chromatographic screening method. It was concluded that tellurium and bismuth were mainly present as inorganic forms and selenium as organic form, and antimony and arsenic species depend on the ingredients of each baby food. Risk assessment considerations were made by comparing dietary intake of the aforementioned elements through the consumption of one baby food portion a day and recommended or tolerable guideline values.
Asunto(s)
Antimonio/análisis , Arsénico/análisis , Bismuto/análisis , Contaminación de Alimentos , Alimentos Infantiles/análisis , Selenio/análisis , Telurio/análisis , Animales , Antimonio/química , Antimonio/toxicidad , Arsénico/química , Arsénico/toxicidad , Arsenicales/efectos adversos , Arsenicales/análisis , Arsenicales/química , Bismuto/química , Bismuto/toxicidad , Exposición Dietética , Contaminantes Ambientales/análisis , Contaminantes Ambientales/química , Contaminantes Ambientales/toxicidad , Peces , Humanos , Lactante , Alimentos Infantiles/efectos adversos , Alimentos Infantiles/economía , Alimentos Infantiles/normas , Estructura Molecular , Nivel sin Efectos Adversos Observados , Valor Nutritivo , Compuestos Organometálicos/análisis , Compuestos Organometálicos/química , Compuestos Organometálicos/toxicidad , Compuestos de Organoselenio/análisis , Compuestos de Organoselenio/química , Medición de Riesgo , Alimentos Marinos/efectos adversos , Alimentos Marinos/análisis , Alimentos Marinos/economía , Alimentos Marinos/normas , Selenio/química , Selenio/envenenamiento , España , Telurio/química , Telurio/toxicidadRESUMEN
Arsenic trioxide (ATO), a component of the traditional Chinese medicine arsenic sublimate, promotes apoptosis and induces leukemic cell differentiation. Combined with all-trans-retinotic acid (ATRA), ATO has become the first-line induction therapy in treating acute promyelocytic leukemia (APL). The most common side effects of ATO include hepatotoxicity, gastrointestinal symptoms, water-sodium retention, and nervous system damage. In this report, we present a rare side effect, rhabdomyolysis, in a 68-year-old female APL patient who was treated with ATO. After taking 10 mg ATO daily for 6 days, she presented shortness of breath, myodynia, elevated creatine kinase, and acute renal insufficiency. This report describes the first case of ATO-induced rhabdomyolysis.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Arsenicales/efectos adversos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Óxidos/efectos adversos , Rabdomiólisis/inducido químicamente , Lesión Renal Aguda/inducido químicamente , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trióxido de Arsénico , Arsenicales/uso terapéutico , Creatinina/sangre , Disnea/etiología , Femenino , Humanos , Medicina Tradicional China , Óxidos/uso terapéutico , Rabdomiólisis/fisiopatologíaRESUMEN
Population of India and Bangladesh and many other parts of the world are badly exposed to arsenic through drinking water. Due to non-availability of safe drinking water, they are dependent on arsenic-contaminated water. Generally, poverty level is high in those areas with lack of proper nutrition. Arsenic is considered to be an environmental contaminant and widely distributed in the environment due to its natural existence and anthropogenic applications. Contamination of arsenic in both human and animal could occur through air, soil, and other sources. Arsenic exposure mainly occurs in food materials through drinking water with high levels of arsenic in it. High levels of arsenic in groundwater have been found to be associated with various health-related problems including arsenicosis, skin lesions, cardiovascular diseases, reproductive problems, psychological, neurological, immunotoxic, and carcinogenesis. The mechanism of arsenic toxicity consists in its transformation in metaarsenite, which acylates protein sulfhydryl groups, affect on mitochondria by inhibiting succinic dehydrogenase activity and can uncouple oxidative phosphorylation with production of active oxygen species by tissues. A variety of dietary antioxidant supplements are useful to protect the carcinogenetic effects of arsenic. They play crucial role for counteracting oxidative damage and protect carcinogenesis by chelating with heavy metal moiety. Phytochemicals and chelating agents will be beneficial for combating heavy metal-induced carcinogenesis through its biopharmaceutical properties.
Asunto(s)
Anticarcinógenos/uso terapéutico , Antioxidantes/uso terapéutico , Arsenicales/efectos adversos , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/efectos de los fármacos , Quelantes/uso terapéutico , Contaminantes Ambientales/efectos adversos , Neoplasias/inducido químicamente , Neoplasias/prevención & control , Animales , Apoptosis/efectos de los fármacos , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Daño del ADN/efectos de los fármacos , Suplementos Dietéticos , Exposición a Riesgos Ambientales/efectos adversos , Contaminación de Alimentos , Humanos , Mutación , Neoplasias/genética , Neoplasias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Medición de Riesgo , Factores de Riesgo , Contaminantes Químicos del Agua/efectos adversos , Abastecimiento de AguaRESUMEN
Realgar-containing Niuhuang Jiedu tablet (NHJD) has been applied in clinic for more than 800 years. However, because realgar contains arsenic (As), it has aroused wide concerns and controversies both at home and abroad. Currently, there are two misunderstandings about realgar-containing Chinese patent medicines. First, some people exaggerated realgar's toxicity as that of arsenic. Second, they recommended to remove realgar from traditional Chinese medicine compounds. In this paper, the authors summarized the advance in studies on NHJD, and proposed different opinions: (1) It is inappropriate to take total As as the index in safety evaluation of NHJD. (2) The toxicity of NHJD is dependent on the dose and duration of administration. (3) Realgar is an active ingredient of NHJD, and shall be deeply studied. Classic realgar-containing traditional Chinese medicine prescriptions, such as Niuhuang Jiedu tablet, shall be evaluated with rigorous modern scientific basis, with the aim to guide rational and safe application.
Asunto(s)
Arsenicales/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China/métodos , Sulfuros/uso terapéutico , Animales , Arsenicales/efectos adversos , Arsenicales/química , Productos Biológicos , Química Farmacéutica/métodos , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/efectos adversos , Medicamentos Herbarios Chinos/química , Humanos , Medicina Tradicional China/efectos adversos , Sulfuros/efectos adversos , Sulfuros/química , Comprimidos , Factores de Tiempo , Resultado del TratamientoRESUMEN
In the past decade, the therapeutic potential of arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL) was recognized. This encouraged other investigators to test the efficacy of ATO in the management of other hematological and solid tumor malignancies. Notably, as a single agent, arsenic trioxide did not benefit patients diagnosed with solid tumors. However, when it was combined with other agents, treatment benefit emerged. In this article, we have summarized the outcome of clinical trials that used arsenic trioxide as a single agent as well as in combination settings in patients diagnosed with solid tumors. We have also reviewed possible additional mechanisms by which ATO may be useful as a chemosensitizer in combination therapy. We hope that our review will encourage clinical investigators to rationally combine ATO with additional chemotherapeutic agents in treating patients diagnosed with solid tumors.
Asunto(s)
Antineoplásicos/uso terapéutico , Arsenicales/uso terapéutico , Neoplasias/tratamiento farmacológico , Óxidos/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Apoptosis/efectos de los fármacos , Trióxido de Arsénico , Arsenicales/administración & dosificación , Arsenicales/efectos adversos , Arsenicales/farmacología , Encefalopatías/inducido químicamente , Ensayos Clínicos como Asunto , Terapia Combinada , Aprobación de Drogas , Sinergismo Farmacológico , Proteínas Hedgehog/fisiología , Enfermedades Hematológicas/inducido químicamente , Humanos , Medicina Tradicional China , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Fusión Oncogénica/antagonistas & inhibidores , Óxidos/administración & dosificación , Óxidos/efectos adversos , Óxidos/farmacología , Radioterapia Adyuvante , Transducción de Señal/efectos de los fármacos , Timidilato Sintasa/antagonistas & inhibidores , Factores de Transcripción/antagonistas & inhibidores , Resultado del Tratamiento , Estados Unidos , United States Food and Drug Administration , Proteína con Dedos de Zinc GLI1RESUMEN
Arsenic trioxide (As(2)O(3)) is an effective drug in the treatment of leukaemia and many solid tumours. In clinical trials, arsenic therapy is closely associated with hepatic toxicity. The present study was designed to investigate the efficacy of omega-3 fatty acid against As(2)O(3)-induced hepatotoxicity. A 4 mg/kg body weight (bw) of As(2)O(3) was orally administered to Wistar male rats for 45 days. Hepatotoxicity was evaluated by biochemical tests, antioxidant assays and histopathological examinations. Arsenic accumulation was found in the liver tissue of rats treated with As(2)O(3). Hepatoprotective efficacy of omega-3 fatty acid was analysed by the combination therapy with As(2)O(3). In vivo studies revealed a significant rise in lipid peroxidation with concomitant decline in reduced glutathione, glutathione-dependant antioxidant enzymes and antiperoxidative enzymes in the liver tissue of rats treated with arsenic. The supplementation of omega-3 fatty acid at a dose of 50 mg/kg bw with As(2)O(3) offers ameliorative effect against hepatocellular toxicity. Omega-3 fatty acid maintained hepatic marker enzymes, antioxidant enzymes and decreased lipid peroxidation. The combination treatment clearly reduced the hepatic structural abnormalities such as haemorrhage, necrosis and cholangiofibrosis in the rats treated with arsenic. This study concludes that the omega-3 fatty acid might be useful for the protection against As(2)O(3)-induced hepatotoxicity.
Asunto(s)
Arsenicales/efectos adversos , Ácidos Grasos Omega-3/farmacología , Hígado/efectos de los fármacos , Óxidos/efectos adversos , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Animales , Antioxidantes/farmacología , Trióxido de Arsénico , Aspartato Aminotransferasas/sangre , Peso Corporal , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Relación Dosis-Respuesta a Droga , Glutatión/metabolismo , L-Lactato Deshidrogenasa/sangre , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratas , Ratas WistarRESUMEN
PURPOSE: This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of an oral tetra-arsenic tetra-sulfide (As4S4) -containing formula named the Realgar-Indigo naturalis formula (RIF) compared with intravenous arsenic trioxide (ATO) as both induction and maintenance therapies for newly diagnosed acute promyelocytic leukemia (APL). PATIENTS AND METHODS: In all, 242 patients with APL were randomly assigned (1:1) to oral RIF (60 mg/kg) or ATO (0.16 mg/kg) combined with all-trans retinoic acid (ATRA; 25 mg/m(2)) during induction therapy. After achieving complete remission (CR), all patients received three courses of consolidation chemotherapy and maintenance treatment with sequential ATRA followed by either RIF or ATO for 2 years. The primary end point was the rate of disease-free survival (DFS) at 2 years, which was assessed for noninferiority with a 10% noninferiority margin. RESULTS: The median follow-up time was 39 months. DFS at 2 years was 98.1% (106 of 108) in the RIF group and 95.5% (107 of 112) in the ATO group. The DFS difference was 2.6% (95% CI, -3.0% to 8.0%). The lower limit of the 95% CI of DFS difference was greater than the -10% noninferiority margin, confirming noninferiority (P < .001). No significant differences were noted between the RIF and ATO groups with regard to the CR rate (99.1% v 97.2%; P = .62) or the overall survival at 3 years (99.1% v 96.6%; P = .18). The rates of adverse events were similar in the two groups. CONCLUSION: Oral RIF plus ATRA is not inferior to intravenous ATO plus ATRA as first-line treatment of APL and may be considered as a routine treatment option for appropriate patients.