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International Journal of Molecular... Nov 2023Cisplatin is a commonly used chemotherapeutic agent with proven efficacy in treating various malignancies, including testicular, ovarian, cervical, breast, bladder, head... (Review)
Review
Cisplatin is a commonly used chemotherapeutic agent with proven efficacy in treating various malignancies, including testicular, ovarian, cervical, breast, bladder, head and neck, and lung cancer. Cisplatin is also used to treat tumors in children, such as neuroblastoma, osteosarcoma, and hepatoblastoma. However, its clinical use is limited by severe side effects, including ototoxicity, nephrotoxicity, neurotoxicity, hepatotoxicity, gastrointestinal toxicity, and retinal toxicity. Cisplatin-induced ototoxicity manifests as irreversible, bilateral, high-frequency sensorineural hearing loss in 40-60% of adults and in up to 60% of children. Hearing loss can lead to social isolation, depression, and cognitive decline in adults, and speech and language developmental delays in children. Cisplatin causes hair cell death by forming DNA adducts, mitochondrial dysfunction, oxidative stress, and inflammation, culminating in programmed cell death by apoptosis, necroptosis, pyroptosis, or ferroptosis. Contemporary medical interventions for cisplatin ototoxicity are limited to prosthetic devices, such as hearing aids, but these have significant limitations because the cochlea remains damaged. Recently, the U.S. Food and Drug Administration (FDA) approved the first therapy, sodium thiosulfate, to prevent cisplatin-induced hearing loss in pediatric patients with localized, non-metastatic solid tumors. Other pharmacological treatments for cisplatin ototoxicity are in various stages of preclinical and clinical development. This narrative review aims to highlight the molecular mechanisms involved in cisplatin-induced ototoxicity, focusing on cochlear inflammation, and shed light on potential antioxidant and anti-inflammatory therapeutic interventions to prevent or mitigate the ototoxic effects of cisplatin. We conducted a comprehensive literature search (Google Scholar, PubMed) focusing on publications in the last five years.
Topics: Humans; Child; Cisplatin; Antineoplastic Agents; Ototoxicity; Hearing Loss; Osteosarcoma; Deafness; Bone Neoplasms; Inflammation
PubMed: 38003734
DOI: 10.3390/ijms242216545 -
Journal of Clinical Oncology : Official... Jun 2024Hearing loss occurs in 50%-70% of children treated with cisplatin. Scientific efforts have led to the recent approval of a pediatric formula of intravenous sodium... (Review)
Review
PURPOSE
Hearing loss occurs in 50%-70% of children treated with cisplatin. Scientific efforts have led to the recent approval of a pediatric formula of intravenous sodium thiosulfate (STS) for otoprotection by the US Food and Drug Administration, the European Medicines Agency, and the Medicines and Health Regulatory Authority in the United Kingdom. To inform stakeholders regarding the clinical utility of STS, the current review summarizes available literature on the efficacy, pharmacokinetics (PK), and safety of systemic STS to minimize cisplatin-induced hearing loss (CIHL).
DESIGN
A comprehensive narrative review is presented.
RESULTS
Thirty-one articles were summarized. Overall, systemic STS effectively reduces CIHL in the preclinical and controlled clinical study settings, in both adults and children with cancer. The extent of CIHL reduction depends on the timing and dosing of STS in relation to cisplatin. Both preclinical and clinical data suggest that systemic STS may affect plasma platinum levels, but studies are inconclusive. Delayed systemic administration of STS, at 6 hours after the cisplatin infusion, does not affect cisplatin-induced inhibition of tumor growth or cellular cytotoxicity in the preclinical setting, nor affect cisplatin efficacy and survival in children with localized disease in the clinical setting.
CONCLUSION
Systemic administration of STS effectively reduces the development and degree of CIHL in both the preclinical and clinical settings. More studies are needed on the PK of STS and cisplatin drug combinations, the efficacy and safety of STS in patients with disseminated disease, and the ability of STS to prevent further deterioration of pre-established hearing loss.
Topics: Humans; Thiosulfates; Neoplasms; Cisplatin; Antineoplastic Agents; Hearing Loss; Child
PubMed: 38648563
DOI: 10.1200/JCO.23.02353 -
Clinical Toxicology (Philadelphia, Pa.) Aug 2021Sodium azide is a highly toxic chemical. Its production has increased dramatically over the last 30 years due to its widespread use in vehicular airbags, and it is...
CONTEXT
Sodium azide is a highly toxic chemical. Its production has increased dramatically over the last 30 years due to its widespread use in vehicular airbags, and it is available for purchase online. Thus, accidental exposure to azide or use as a homicidal or suicidal agent could be on the rise, and secondary exposure to medical personnel can occur. No antidote exists for azide poisoning. We conducted a systematic review of azide poisoning to assess recent poisoning reports, exposure scenarios, clinical presentations, and treatment strategies.
METHODS
We searched both medical and newspaper databases to review the literature between 01/01/2000 and 12/31/2020, pairing the controlled vocabulary and keyword terms "sodium azide" or "hydrazoic acid" with terms relating to exposures and outcomes, such as "ingestion," "inhalation," "exposure," "poisoning," and "death." We included all peer-reviewed papers and news articles describing human azide poisoning cases from English and non-English publications that could be identified using English keywords. Data abstracted included the number, age, and gender of cases, mode of exposure, exposure setting, azide dose and route of exposure, symptoms, outcome, and treatment modalities.
RESULTS
We identified 663 peer-reviewed papers and 303 newspaper articles. After removing duplicated and non-qualifying sources, 54 publications were reviewed describing 156 cases, yielding an average of 7.8 reported azide poisoning cases per year. This rate is three times higher than in a previous review covering the period of 1927 to 1999. Poisoning occurred most commonly in laboratory workers, during secondary exposure of medical personnel, or from a ripped airbag. Hypotension occurred commonly, in some cases requiring vasopressors and one patient received an intra-aortic ballon pump. Gastric lavage and/or activated charcoal were used for oral azide ingestion, and sodium nitrite, sodium thiosulfate, and/or hydroxocobalamin were used in severely poisoned patients.
CONCLUSIONS
Recent increases in azide poisoning reports may stem from greater commercial use and availability. Treatment of systemic poisoning may require aggressive hemodynamic support due to profound hypotension. Based on mechanistic considerations, hydroxocobalamin is a rational choice for treating azide poisoning.
Topics: Adult; Aged; Antidotes; Female; Humans; Hypotension; Male; Middle Aged; Occupational Exposure; Poisoning; Sodium Azide; Sodium Nitrite; Suicide, Attempted; Thiosulfates
PubMed: 34128439
DOI: 10.1080/15563650.2021.1906888 -
ACS Nano Dec 2023As the prevalence of vascular calcification (VC), a strong contributor to cardiovascular morbidity and mortality, continues to increase, the need for pharmacologic...
As the prevalence of vascular calcification (VC), a strong contributor to cardiovascular morbidity and mortality, continues to increase, the need for pharmacologic therapies becomes urgent. Sodium thiosulfate (STS) is a clinically approved drug for therapy against VC; however, its efficacy is hampered by poor bioavailability and severe adverse effects. Plant-derived extracellular vesicles have provided options for VC treatment since they can be used as biomimetic drug carriers with higher biosafety and targeting abilities than artificial carriers. Inspired by natural grapefruit-derived extracellular vesicles (EVs), we fabricated a biomimetic nanocarrier comprising EVs loaded with STS and further modified with hydroxyapatite crystal binding peptide (ESTP) for VC-targeted delivery of STS. , the ESTP nanodrug exhibited excellent cellular uptake capacity by calcified vascular smooth muscle cells (VSMCs) and subsequently inhibited VSMCs calcification. In the VC mice model, the ESTP nanodrug showed preferentially the highest accumulation in the calcified arteries compared to other treatment groups. Mechanistically, the ESTP nanodrug significantly prevented VC via driving M2 macrophage polarization, reducing inflammation, and suppressing bone-vascular axis as demonstrated by inhibiting osteogenic phenotype trans-differentiation of VSMCs while enhancing bone quality. In addition, the ESTP nanodrug did not induce hemolysis or cause any damage to other organs. These results suggest that the ESTP nanodrug can prove to be a promising agent against VC without the concern of systemic toxicity.
Topics: Animals; Mice; Citrus paradisi; Biomimetics; Vascular Calcification; Extracellular Vesicles
PubMed: 38055864
DOI: 10.1021/acsnano.3c05261 -
Archives of Dermatological Research Aug 2022Calcinosis cutis is a deposition of calcium in the skin and subcutaneous tissue, often accompanied by pain, reduced mobility, and chronic infections. Limited evidence is... (Review)
Review
Calcinosis cutis is a deposition of calcium in the skin and subcutaneous tissue, often accompanied by pain, reduced mobility, and chronic infections. Limited evidence is available about the feasibility and efficacy of therapies alternative to systemic treatment and surgical excision, both of which often lead to unsatisfactory results or complications. We conducted a systematic review to evaluate the efficacy and safety of topical and intralesional sodium thiosulfate, extracorporeal shock-wave lithotripsy (ESWL), and laser for calcinosis cutis. PubMed, Embase, and Web of Science were searched. Reports of calciphylaxis and treatment combined with systemic medications were excluded. A total of 40 studies including 136 patients were analysed. Partial or complete remission after monotherapy was observed in 64% to 81% of cases. Self-applied topical sodium thiosulfate required patient's adherence (mean treatment duration, 4.9 months; range 2-24). Laser therapy enabled complete remission of microcalcifications after a single procedure (57%; 12/21). ESWL and intralesional sodium thiosulfate injections decreased calcinosis-associated pain (median reduction in VAS score, 3; range 0-9 and 1; range 0-5, respectively). The most common adverse event was scarring and hyperkeratosis, observed after CO laser (56%; 10/18). Intralesional sodium thiosulfate injections caused transient pain in over 11% of patients. Recurrences within the follow-up were rare (2%; 3/136). This study provides an overview of minimally invasive and local therapies that in selected cases might transcend conventional treatment. The limitation of this study is the poor level of evidence, which emerges mainly from non-randomized studies at high risk of bias.
Topics: Administration, Cutaneous; Calcinosis; Humans; Immunotherapy; Pain; Remission Induction
PubMed: 34165603
DOI: 10.1007/s00403-021-02264-5 -
Best Practice & Research. Clinical... Jun 2022Calcinosis, insoluble calcium compounds deposited in skin and other tissues, is a crippling sequela of dermatomyositis. Prolonged disease associated with ongoing... (Review)
Review
Calcinosis, insoluble calcium compounds deposited in skin and other tissues, is a crippling sequela of dermatomyositis. Prolonged disease associated with ongoing inflammation, ischemia, repetitive trauma, and certain autoantibodies are associated with calcinosis. Herein, we describe potential pathogenic mechanisms including the role of mitochondrial calcification. There are no widely effective treatments for calcinosis. We review available pharmacologic therapies for calcinosis including those targeting calcium and phosphorus metabolism; immunosuppressive/anti-inflammatory therapies; and vasodilators. Mounting evidence supports the use of various formulations of sodium thiosulfate in the treatment of calcinosis. Although the early institution of aggressive immunosuppression may prevent calcinosis in juvenile dermatomyositis, only limited data support improvement once it has developed. Minocycline can be useful particularly for lesions associated with surrounding inflammation. Powerful vasodilators, such as prostacyclin analogs, may have promise in the treatment of calcinosis, but further studies are necessary. Surgical removal of lesions when amenable is our treatment of choice.
Topics: Anti-Inflammatory Agents; Autoantibodies; Calcinosis; Calcium; Dermatomyositis; Humans; Inflammation; Minocycline; Phosphorus; Prostaglandins I; Vasodilator Agents
PubMed: 35803868
DOI: 10.1016/j.berh.2022.101768 -
Kidney & Blood Pressure Research 2021Arterial stenosis activates the renin-angiotensin-aldosterone system subsequently resulting in renovascular hypertension (RVHT) and renal oxidative injury. We explored...
BACKGROUND/AIMS
Arterial stenosis activates the renin-angiotensin-aldosterone system subsequently resulting in renovascular hypertension (RVHT) and renal oxidative injury. We explored the effect of sodium thiosulfate (STS, Na2S2O3), a developed antioxidant in clinical trial, on RVHT-induced hypertension and renal oxidative injury in rats.
METHODS
We induced RVHT in male Wistar rats with bilaterally partial ligation of renal arteries in the 2-kidney 2-clip model. We evaluated the STS effect on RVHT-induced oxidative injury and apoptosis by a chemiluminescence amplification method, Western blot, and immunohistochemistry.
RESULTS
We found STS displayed a dose-dependent antioxidant H2O2 activity and adapted the maximal scavenging H2O2 activity of STS at the dosage of 0.1 g/kg intraperitoneally 3 times/week for 4 weeks in RVHT rats. RVHT induced a significant elevation of arterial blood pressure, blood reactive oxygen species amount, neutrophil infiltration, 4-HNE and NADPH oxidase gp91 expression, Bax/Bcl-2/poly(ADP-ribose) polymerase (PARP)-mediated apoptosis formation, blue Masson-stained fibrosis, and urinary protein level. STS treatment significantly reduced hypertension, oxidative stress, neutrophil infiltration, fibrosis, and Bax/Bcl-2/PARP-mediated apoptosis formation and depressed the urinary protein level in the RVHT models.
CONCLUSION
Our results suggest that STS treatment could ameliorate RVHT hypertension and renal oxidative injury through antioxidant, antifibrotic, and antiapoptotic mechanisms.
Topics: Animals; Antioxidants; Blood Pressure; Hypertension, Renovascular; Kidney; Male; Oxidative Stress; Rats, Wistar; Reactive Oxygen Species; Thiosulfates; Rats
PubMed: 33326967
DOI: 10.1159/000510047 -
Medicina (Kaunas, Lithuania) Jul 2023Limited data are available on the utilization of sodium thiosulfate (STS) treatment for calciphylaxis in peritoneal dialysis (PD) patients, while it is well-studied in... (Review)
Review
Limited data are available on the utilization of sodium thiosulfate (STS) treatment for calciphylaxis in peritoneal dialysis (PD) patients, while it is well-studied in hemodialysis (HD) patients. A systematic literature search was conducted using Ovid MEDLINE, EBM Reviews-Cochrane Central Register of Controlled Trials, and EBM Reviews-Cochrane Database of Systematic Reviews to identify reported cases of PD patients with calciphylaxis who received STS. The search covered the inception of the databases through August 2022. Across 19 articles, this review identified 30 PD patients with calciphylaxis who received STS. These included 15 case reports, 2 case series, and 2 cohort studies. The administration routes and doses varied depending on the study. For intravenous (IV) administration ( = 18), STS doses ranged from 3.2 g twice daily to 25 g three times weekly for 5 weeks to 8 months. Outcomes included 44% of patients experiencing successful wound healing, 6% discontinuing STS due to adverse effects, 67% transitioning to HD, and 50% dying from calciphylaxis complications. For intraperitoneal (IP) administration ( = 5), STS doses ranged from 12.5 to 25 g three to four times weekly for 12 h to 3 months. Results showed 80% of patients achieving successful wound healing, 80% discontinuing STS due to adverse effects, 40% transitioning to HD, and 20% dying from IP STS-related chemical peritonitis. In cases where patients switched from IV to IP STS ( = 3), doses ranged from 12.5 to 25 g two to three times weekly for 2.5 to 5 months. Among them, 67% experienced successful wound healing, while 33% died from sepsis. Two cases utilized oral STS at a dose of 1500 mg twice daily for 6 and 11 months, resulting in successful wound healing without adverse effects or need for HD. However, one patient (50%) died due to small bowel obstruction. This systematic review provides an overview of STS treatment for PD patients with calciphylaxis. Although successful treatment cases exist, adverse effects were significant. Further research, including larger clinical studies and pharmacokinetic data, is necessary to establish the optimal route, dose, and efficacy of STS in PD patients.
Topics: Humans; Calciphylaxis; Peritoneal Dialysis; Renal Dialysis
PubMed: 37512116
DOI: 10.3390/medicina59071306 -
Clinical Toxicology (Philadelphia, Pa.) Mar 2022Hydrogen cyanide and methanethiol are two toxic gases that inhibit mitochondrial cytochrome oxidase. Cyanide is generated in structural fires and methanethiol is...
CONTEXT
Hydrogen cyanide and methanethiol are two toxic gases that inhibit mitochondrial cytochrome oxidase. Cyanide is generated in structural fires and methanethiol is released by decaying organic matter. Current treatments for cyanide exposure do not lend themselves to treatment in the field and no treatment exists for methanethiol poisoning. Sodium tetrathionate (tetrathionate), a product of thiosulfate oxidation, could potentially serve as a cyanide antidote, and, based on its chemical structure, we hypothesized it could react with methanethiol.
RESULTS
We show that tetrathionate, unlike thiosulfate, reacts directly with cyanide under physiological conditions, and based on rabbit studies where we monitor cyanide poisoning in real-time, tetrathionate likely reacts directly with cyanide . We found that tetrathionate administered by intramuscular injection rescues >80% of juvenile, young adult, and old adult mice from exposure to inhaled hydrogen cyanide gas that is >80% lethal. Tetrathionate also rescued young adult rabbits from intravenously administered sodium cyanide. Tetrathionate was reasonably well-tolerated by mice and rats, yielding a therapeutic index of ∼5 in juvenile and young adult mice, and ∼3.3 in old adult mice; it was non-mutagenic in Chinese Hamster ovary cells and by the Ames bacterial test. We found by gas chromatography-mass spectrometry that both tetrathionate and thiosulfate react with methanethiol to generate dimethyldisulfide, but that tetrathionate was much more effective than thiosulfate at recovering intracellular ATP in COS-7 cells and rescuing mice from a lethal exposure to methanethiol gas.
CONCLUSION
We conclude that tetrathionate has the potential to be an effective antidote against cyanide and methanethiol poisoning.
Topics: Animals; Antidotes; CHO Cells; Cricetinae; Cricetulus; Cyanides; Humans; Mice; Rabbits; Rats; Sulfhydryl Compounds; Tetrathionic Acid; Thiosulfates
PubMed: 34328378
DOI: 10.1080/15563650.2021.1953517 -
The New England Journal of Medicine Sep 2018
Topics: Antineoplastic Agents; Cisplatin; Deafness; Hearing Loss; Humans; Thiosulfates
PubMed: 30260148
DOI: 10.1056/NEJMc1809501