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Biomedicine & Pharmacotherapy =... Jun 2020Tannic acid (TA), a group of polyphenolic compounds, has multiple anticancer, antimutagenic, antioxidant and anti-inflammatory activities. However, the effects of TA on...
BACKGROUND AND PURPOSE
Tannic acid (TA), a group of polyphenolic compounds, has multiple anticancer, antimutagenic, antioxidant and anti-inflammatory activities. However, the effects of TA on arsenic trioxide (ATO)-induced nephrotoxicity are still relatively unknown. This study investigated the protective effects and potential mechanisms of TA on ATO-induced nephrotoxicity in rats.
METHODS
Rats were intragastrically administered TA with concurrent ATO infused intraperitoneally over 10 days. Renal morphology changes were observed through light microscopy. The levels of antioxidants and pro-inflammatory factors were measured in the serum and renal tissue, respectively. Further, expression of B-cell lymphoma-2, B-cell lymphoma-extra large, p53, and Bcl-2-associated X protein were measured using an immunohistochemical method. The protein expression of nuclear factor kappa B (NF-κB), nuclear factor-erythroid-2-related factor 2 (Nrf2), and kelch-like ECH-associated protein 1 (Keap1) were measured by Western blot.
RESULTS
The data showed that ATO exposure significantly increased the serum nephritic, oxidative stress, apoptosis and inflammatory markers in the renal tissue of rats. Conversely, pretreatment with TA reversed these changes. Furthermore, TA treatment caused a significant decrease in NF-κB expression (P < 0.05), while increasing Nrf2 and Keap1 expressions (P < 0.05).
CONCLUSION
TA ameliorates ATO-induced nephrotoxicity, which is related to the inhibition of oxidative stress, inflammation and apoptosis, potentially through the NF-κB/Nrf2 pathway.
Topics: Animals; Antioxidants; Apoptosis; Arsenic Trioxide; Disease Models, Animal; Inflammation; Interleukins; Kidney; Kidney Diseases; Male; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Rats; Tannins
PubMed: 32146384
DOI: 10.1016/j.biopha.2020.110047 -
Current Opinion in Chemical Biology Feb 2023Arsenic trioxide (ATO) is an approved therapy for the treatment of acute promyelocytic leukemia, but the extension of arsenic-based therapies to other types of... (Review)
Review
Arsenic trioxide (ATO) is an approved therapy for the treatment of acute promyelocytic leukemia, but the extension of arsenic-based therapies to other types of malignancies, notably tumor-forming cancers, has been slow. Nanodelivery vehicles offer a means of effectively delivering ATO to tumors. Very recently, there has been a series of developments in the formulation of arsenic-based nanomedicines that are not simply loaded with ATO. Realgar nanoparticles are comprised of molecular AsS units. Current studies suggest that realgar nanoparticles ultimately act in a manner similar to ATO, but with greatly attenuated toxic side effects. A drastically different approach is taken with arsenene nanosheets, a 2-dimensional form of elemental As. The electronic properties of this material allow it to mediate both photothermal therapy and photodynamic therapy. The exploration of these nanomaterials is still in its infancy but is poised to allow arsenic-based therapy to make yet another significant impact on cancer treatment.
Topics: Arsenic; Oxides; Antineoplastic Agents; Arsenic Trioxide; Nanoparticles
PubMed: 36413888
DOI: 10.1016/j.cbpa.2022.102229 -
International Journal of Hyperthermia :... 2022Angiogenesis occurs during tumor progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA). Arsenic trioxide (ATO) shows promising...
OBJECTIVES
Angiogenesis occurs during tumor progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA). Arsenic trioxide (ATO) shows promising therapeutic potential in advanced HCC. Whether ATO regulates angiogenesis and can be used to prevent tumor progression in HCC after insufficient RFA is still unknown.
METHODS
Insufficient RFA was simulated using a water bath. MTT assay and tube formation assay were used to evaluate the effects of ATO on viability and proangiogenic abilities of SMMC7721 and HepG2 cells after insufficient RFA . The molecular changes with the treatment of ATO were evaluated through Western blot. An ectopic nude mice model was used to evaluate the effect of ATO on the tumor of SMMC7721 cells after insufficient RFA.
RESULTS
In this study, HepG2 and SMMC7721 cells after insufficient RFA (named HepG2-H and SMMC7721-H, respectively) showed higher proliferation than the untreated cells and promoted tube formation of endothelial cells in a paracrine manner. ATO eliminated the difference in proliferation between untreated and RFA-treated cells and suppressed angiogenesis induced by HCC cells after insufficient RFA through the Ang-1 (angiopoietin-1)/Ang-2 (angiopoietin-2)/Tie2 pathway. Hif-1α overexpression abolished the inhibitory effect of ATO on angiogenesis in HCC after insufficient RFA. ATO inhibited tumor growth and angiogenesis in HCC after insufficient RFA.
CONCLUSIONS
Our results demonstrate that ATO blocks the paracrine signaling of Ang-1 and Ang-2 by inhibiting p-Akt/Hif-1α and further suppresses the angiogenesis of HCC after insufficient RFA.
Topics: Angiopoietin-1; Angiopoietin-2; Animals; Arsenic Trioxide; Carcinoma, Hepatocellular; Cell Line, Tumor; Endothelial Cells; Liver Neoplasms; Mice; Mice, Nude; Neovascularization, Pathologic; Radiofrequency Ablation
PubMed: 35848416
DOI: 10.1080/02656736.2022.2093995 -
Blood Aug 2019Arsenic trioxide and all- retinoic acid have become the frontline treatments for patients with acute promyelocytic leukemia (APL). Despite the long wait for an oral... (Review)
Review
Arsenic trioxide and all- retinoic acid have become the frontline treatments for patients with acute promyelocytic leukemia (APL). Despite the long wait for an oral arsenic drug, a commercially available agent, realgar-indigo naturalis formula (RIF), was not launched in China until 2009. Since then, over 5000 APL patients have been treated with oral RIF in China. Oral arsenic not only shows a clinical efficacy comparable to that of IV formulations but also displays a better safety profile, improved quality of life, and lower medical costs for patients. The promising results promote incorporating an outpatient postremission therapy model into clinical practice for both low-risk and high-risk APL patients in China. In this review, we discuss the evolution of oral arsenic RIF in the treatment of APL, with a special focus on how to address the related complications during induction therapy.
Topics: Administration, Oral; Antineoplastic Agents; Arsenic; Arsenic Trioxide; Chemical and Drug Induced Liver Injury; China; Diarrhea; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis
PubMed: 31113776
DOI: 10.1182/blood.2019000760 -
The Journal of Biological Chemistry Jul 2009Arsenic is a metalloid that generates various biological effects on cells and tissues. Depending on the specific tissue exposed and the time and degree of exposure,... (Review)
Review
Arsenic is a metalloid that generates various biological effects on cells and tissues. Depending on the specific tissue exposed and the time and degree of exposure, diverse responses can be observed. In humans, prolonged and/or high dose exposure to arsenic can have a variety of outcomes, including the development of malignancies, severe gastrointestinal toxicities, diabetes, cardiac arrhythmias, and death. On the other hand, one arsenic derivative, arsenic trioxide (As(2)O(3)), has important antitumor properties. This agent is a potent inducer of antileukemic responses, and it is now approved by the Food and Drug Administration for the treatment of acute promyelocytic leukemia in humans. The promise and therapeutic potential of arsenic and its various derivatives have been exploited for hundreds of years. Remarkably, research focused on the potential use of arsenic compounds in the treatment of human diseases remains highly promising, and it is an area of active investigation. An emerging approach of interest and therapeutic potential involves efforts to target and block cellular pathways activated in a negative feedback manner during treatment of cells with As(2)O(3). Such an approach may ultimately provide the means to selectively enhance the suppressive effects of this agent on malignant cells and render normally resistant tumors sensitive to its antineoplastic properties.
Topics: Antineoplastic Agents; Apoptosis; Arsenic; Arsenic Trioxide; Arsenicals; Cell Death; Cell Line, Tumor; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Models, Biological; Models, Chemical; Neoplasms; Oxides; Signal Transduction
PubMed: 19363033
DOI: 10.1074/jbc.R900003200 -
Human & Experimental Toxicology 2022Arsenic trioxide (ATO) has been found to be effective in acute promyelocytic leukemia. However, ATO-induced severe cardiotoxicity limits its clinical application. To...
Arsenic trioxide (ATO) has been found to be effective in acute promyelocytic leukemia. However, ATO-induced severe cardiotoxicity limits its clinical application. To date, the mechanisms of ATO-induced cardiotoxicity remain unclear. It is hypothesized that ferroptosis may trigger ATO-induced cardiotoxicity; however, this has not yet been investigated. To clarify this hypothesis, rat cardiomyocyte H9c2 cells were treated with ATO with or without ferrostain-1 (Fer-1). The results indicated that ATO exposure induced H9c2 cell death and apoptosis, and the ferroptosis inhibitor Fer-1, administered for 24 h before ATO exposure, suppressed ATO-induced cell death, and apoptosis, as determined by Annexin V-APC/7-AAD apoptosis assay. Furthermore, Fer-1 displayed a cardioprotective effect through inhibiting the ATO-induced production of intracellular reactive oxygen species, improving the ATO-induced loss of the mitochondrial membrane potential, alleviating hyperactive endoplasmic reticulum stress, and alleviating the ATO-induced impairment in autophagy in H9c2 cells. Overall, the cardioprotective effect of Fer-1 against ATO-induced cell injury implies that ATO may trigger ferroptosis to induce cardiotoxicity. These findings lay the foundation for exploring the potential value of ferroptosis inhibitors against ATO-induced cardiotoxicity in the future.
Topics: Animals; Arsenic Trioxide; Cardiotoxicity; Cell Death; Cells, Cultured; Ferroptosis; Humans; Myocytes, Cardiac; Rats
PubMed: 35195477
DOI: 10.1177/09603271211064537 -
Inorganic Chemistry Nov 2013Starting in ancient China and Greece, arsenic-containing compounds have been used in the treatment of disease for over 3000 years. They were used for a variety of... (Review)
Review
Starting in ancient China and Greece, arsenic-containing compounds have been used in the treatment of disease for over 3000 years. They were used for a variety of diseases in the 20th century, including parasitic and sexually transmitted illnesses. A resurgence of interest in the therapeutic application of arsenicals has been driven by the discovery that low doses of a 1% aqueous solution of arsenic trioxide (i.e., arsenous acid) lead to complete remission of certain types of leukemia. Since Food and Drug Administration (FDA) approval of arsenic trioxide (As2O3) for treatment of acute promyelocytic leukemia in 2000, it has become a front-line therapy in this indication. There are currently over 100 active clinical trials involving inorganic arsenic or organoarsenic compounds registered with the FDA for the treatment of cancers. New generations of inorganic and organometallic arsenic compounds with enhanced activity or targeted cytotoxicity are being developed to overcome some of the shortcomings of arsenic therapeutics, namely, short plasma half-lives and a narrow therapeutic window.
Topics: Antineoplastic Agents; Arsenic; Arsenic Trioxide; Arsenicals; Clinical Trials as Topic; Drug Carriers; Humans; Inactivation, Metabolic; Leukemia, Promyelocytic, Acute; Nanoparticles; Oxides; Sulfhydryl Compounds; Thermodynamics
PubMed: 24147771
DOI: 10.1021/ic401211u -
Cellular & Molecular Immunology Mar 2023
Topics: Humans; Arsenic Trioxide; Necrosis; Apoptosis; Antineoplastic Agents; Arsenicals
PubMed: 36693921
DOI: 10.1038/s41423-023-00976-4 -
Transplantation and Cellular Therapy Oct 2022Chronic graft-versus-host disease (cGVHD) occurs in 20% to 50% of recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Corticosteroids (CS)...
High Response Rate and Corticosteroid Sparing with Arsenic Trioxide-Based First-Line Therapy in Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.
Chronic graft-versus-host disease (cGVHD) occurs in 20% to 50% of recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Corticosteroids (CS) remain the first-line therapy but have suboptimal efficacy and carry a risk of long-term side effects. New agents with a better safety profile and higher efficacy are urgently needed. This study aimed to evaluate the efficacy and safety of a first-line combination of arsenic trioxide (ATO) and CS in adult patients with cGVHD requiring systemic therapy after first allo-HSCT for a hematologic disease. In this prospective national multicenter single-arm open-label Phase II study conducted in 5 university hospital centers in France, ATO was started within 10 days of CS at 1 mg/kg/day. Patients received 11 infusions per cycle of 28 days at a dose of .15 mg/kg per infusion. According to the clinical response and depending on the clinician's opinion, patients received 1 or 2 cycles of treatment. Cycles were separated by an 8- to 11-week interval from the first infusion of ATO. Patients were evaluated at 6 weeks, 14 weeks, 6 months, 9 months, and 12 months after the first ATO infusion, using the Chronic GVHD Activity Assessment Form A. The primary endpoint was preliminary efficacy based on the overall response rate (ORR; complete response [CR] or partial response [PR]) at 6 months. Response rates were estimated with 2-sided 95% exact confidence intervals (CIs). Twenty-one patients entered the study and received at least 1 ATO infusion (1 incomplete cycle for 1 patient, 1 complete cycle for 11 patients, and 2 complete cycles for 9). Six patients continued ongoing cyclosporine A (CsA) treatment after inclusion, and 4 other patients resumed CsA treatment during the study. The ORR at 6 months was 75.0% (95% CI, 50.9% to 91.3%), with CR in 35% and PR in 40%. Failure-free survival was 90.0% (95% CI, 65.6% to 97.4%) at 6 months and 65.0% (95% CI, 40.3% to 81.5%) at 12 months. The progression-free survival rate was 95.0% (95% CI, 69.5% to 99.3%) at 6 months and 83.8% (95% CI, 57.7% to 94.5%) at 12 months. The mean CS dose was decreased by 74.6 ± 32.7% from baseline to the 6-month visit and by 91.0 ± 14.6% from baseline to the 12-month visit. CS was definitively stopped in 30.0% of patients at the 6-month visit and in 47.4% at the 12-month visit. Two patients died, at 7 months and 12 months after the first ATO infusion from causes unrelated to ATO. One patient withdrew because of transient hepatotoxicity. The first-line combination of ATO and CS was associated with a high clinical response rate and rapid CS sparing in cGVHD after previous allo-HSCT.
Topics: Adrenal Cortex Hormones; Adult; Arsenic Trioxide; Cyclosporine; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Prospective Studies
PubMed: 35830931
DOI: 10.1016/j.jtct.2022.07.004 -
Clinical and Applied... 2022Acute promyelocytic leukemia (APL) usually presents with a series of coagulation-anticoagulation disturbance. Early administration of All-trans retinoic acid (ATRA) can... (Review)
Review
Acute promyelocytic leukemia (APL) usually presents with a series of coagulation-anticoagulation disturbance. Early administration of All-trans retinoic acid (ATRA) can reduce the risk of bleeding, but the potential for thrombosis needs to be addressed in some cases. The role of arsenic agent in correcting coagulation disorder remains to be studied, but oral arsenic agent shows potential advantages in coagulation recovery compared with intravenous agent, and chemotherapy can aggravate the progress of coagulation disease. In addition to early application of ATRA, avoiding invasive procedures and transfusion support can reduce the risk of bleeding. Whether the administration of heparin, thrombomodulin, recombinant factor VIIa or antifibrinolytics reduces the risk of bleeding and thrombosis associated with APL remains to be further explored, and their routine use outside of clinical trials is not recommended. This article reviews the effects of related drugs on coagulation-anticoagulation balance in APL patients.
Topics: Antifibrinolytic Agents; Antineoplastic Agents; Arsenic Trioxide; Blood Coagulation; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Thrombosis; Tretinoin
PubMed: 35187963
DOI: 10.1177/10760296221080166