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Japanese Journal of Pharmacology Dec 1981The protective effect of sodium thiosulfate and thiourea on the lethal toxicity of the antitumor drug, cis-diamminedichloroplatinum (II) (cis-DDP), was investigated in...
The protective effect of sodium thiosulfate and thiourea on the lethal toxicity of the antitumor drug, cis-diamminedichloroplatinum (II) (cis-DDP), was investigated in bacteria and mice. Initially, the agents capable of antagonizing bactericidal activity of cis-DDP were screened using WP2 uvra, a strain of E. coli sensitive to this drug. Of the ten sulfur-containing compounds tested, thiourea and sodium thiosulfate exhibited potent protecting effects against cis-DDP cytotoxicity in bacteria. Propylthiouracil and methimazole showed intermediate levels of such protection, but the other 6 compounds had little or no protective effects. Thiourea and sodium thiosulfate were then subjected to the acute lethal toxicity test in mice to assess their protective activity in vivo. We found that cis-DDP i.v. lethality against mice can be blocked almost completely by excess amounts of thiourea or sodium thiosulfate. Thiourea protected against cis-DDP toxicity with a narrow range among the effective doses, while sodium thiosulfate was protective with a remarkably wide range of effective doses. The effectiveness of sodium thiosulfate was also indicated in experiments in which the LD50 dose of cis-DDP (16 mg/kg) i.p. increased over the level of greater than 200 mg/kg with concomitant administration of sodium thiosulfate i.p.
Topics: Animals; Bacteria; Cisplatin; Escherichia coli; Female; Lethal Dose 50; Mice; Mice, Inbred Strains; Thiosulfates; Thiourea
PubMed: 6801366
DOI: 10.1254/jjp.31.883 -
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 -
Journal of Ultrasound Dec 2022Calcinosis cutis (CC) is characterized by deposit of calcium salts in the skin and subcutaneous tissue; its clinical presentation consists of indurated painful nodules,...
Calcinosis cutis (CC) is characterized by deposit of calcium salts in the skin and subcutaneous tissue; its clinical presentation consists of indurated painful nodules, which can ulcerate and become superinfected. CC treatment remains a challenge, yet successful treatment with intralesional (IL) sodium thiosulfate (STS) has been reported in several CC subtypes. Herein we are reporting on a case series of 5 patients with CC successfully treated with IL-STS. We describe the 18-22 MHz ultrasound characteristics of the lesions and on follow-up after treatment. Ultrasound imaging was useful in guiding IL-STS injections and confirming response to treatment.
Topics: Humans; Follow-Up Studies; Thiosulfates; Calcinosis; Ultrasonography
PubMed: 35397096
DOI: 10.1007/s40477-022-00665-4 -
Annals of Surgical Oncology Dec 2023Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin confers a survival benefit in epithelial ovarian cancer (EOC) but is associated with renal toxicity.... (Clinical Trial)
Clinical Trial
PURPOSE
Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin confers a survival benefit in epithelial ovarian cancer (EOC) but is associated with renal toxicity. Sodium thiosulfate (ST) is used for nephroprotection for HIPEC with cisplatin, but standard HIPEC practices vary.
METHODS
A prospective, nonrandomized, clinical trial evaluated safety outcomes of HIPEC with cisplatin 75 mg/m during cytoreductive surgery (CRS) in patients with EOC (n = 34) and endometrial cancer (n = 6). Twenty-one patients received no ST (nST), and 19 received ST. Adverse events (AEs) were reported according to CTCAE v.5.0. Serum creatinine (Cr) was collected preoperatively and postoperatively (Days 5-8). Progression-free survival (PFS) was followed. Normal peritoneum was biopsied before and after HIPEC for whole transcriptomic sequencing to identify RNAseq signatures correlating with AEs.
RESULTS
Forty patients had HIPEC at the time of interval or secondary CRS. Renal toxicities in the nST group were 33% any grade AE and 9% grade 3 AEs. The ST group demonstrated no renal AEs. Median postoperative Cr in the nST group was 1.1 mg/dL and 0.5 mg/dL in the ST group (p = 0.0001). Median change in Cr from preoperative to postoperative levels were + 53% (nST) compared with - 9.6% (ST) (p = 0.003). PFS did not differ between the ST and nST groups in primary or recurrent EOC patients. Renal AEs were associated with downregulation of metabolic pathways and upregulation of immune pathways.
CONCLUSIONS
ST significantly reduces acute renal toxicity associated with HIPEC with cisplatin in ovarian cancer patients. As nephrotoxicity is high in HIPEC with cisplatin, nephroprotective agents should be considered.
Topics: Humans; Female; Cisplatin; Hyperthermic Intraperitoneal Chemotherapy; Antineoplastic Agents; Prospective Studies; Hyperthermia, Induced; Neoplasm Recurrence, Local; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Cytoreduction Surgical Procedures; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy
PubMed: 37710139
DOI: 10.1245/s10434-023-14216-6 -
Intensive Care Medicine Experimental Jan 2020Hydrogen sulfide (HS) has long been known as a toxic environmental hazard. Discovery of physiological roles of HS as a neurotransmitter by Kimura and colleagues... (Review)
Review
Hydrogen sulfide (HS) has long been known as a toxic environmental hazard. Discovery of physiological roles of HS as a neurotransmitter by Kimura and colleagues triggered an intensive research in the biological roles of HS in the past decades. Manipulation of HS levels by inhibiting HS synthesis or administration of HS-releasing molecules revealed beneficial as well as harmful effects of HS. As a result, it is now established that HS levels are tightly controlled and too much or too little HS levels cause harm. Nonetheless, translation of sulfide-based therapy to clinical practice has been stymied due to the very low therapeutic index of sulfide and the incomplete understanding of endogenous sulfide metabolism. One potential strategy to circumvent this problem is to use a safe and stable sulfide metabolite that may mediate effects of HS. Alternatively, endogenous sulfide levels may be controlled using specific sulfide scavengers. In this review article, the role of endogenous HS production and catabolism will be briefly reviewed followed by an introduction of thiosulfate and HS scavengers as novel pharmacological tools to control HS-dependent signaling.
PubMed: 32006269
DOI: 10.1186/s40635-020-0296-4 -
American Journal of Nephrology 2011Treatment strategies for calciphylaxis are limited by inadequate understanding of its pathophysiology. Mortality reaches 80%, due to progressive skin ischemia, necrosis... (Review)
Review
Treatment strategies for calciphylaxis are limited by inadequate understanding of its pathophysiology. Mortality reaches 80%, due to progressive skin ischemia, necrosis and infections. In addition to calcium and parathyroid disorders, hypercoagulability can have a role: primary thrombotic disorders as well as secondary, such as proposed warfarin procoagulant effects. Traditional care addresses the calcium-phosphate-PTH axis: minimizing calcium intake, calcimimetics, cautious vitamin D analogs, strict phosphate control, and surgical parathyroidectomy if necessary. Newer approaches focus on extraosseous mineralization: dissolution of calcium deposits, altering osteoprotegerin and NF-κB pathways, and treating macrophage or cytokine-mediated inflammation. Sodium thiosulfate has reported success, and is thought to be due to enhanced calcium solubility and dialysis clearance. Bisphosphonates may have efficacy by lowering bone turnover or a variety of vascular tissue mechanisms. The literature for both agents is very limited, and optimal dosing regimens remain unclear. Patients responsive to a medication will have decreasing pain in days and lesions beginning to heal within approximately 2 weeks. Due to high mortality, early use of combination therapy is advocated, although specific protocols have not been well established. The often dramatic improvements in case-based literature are very encouraging and will hopefully lead to more rigorous studies.
Topics: Calciphylaxis; Humans
PubMed: 21986387
DOI: 10.1159/000332221 -
BMC Nephrology Jan 2024Up to now, there is no unequivocal intervention to mitigate vascular calcification (VC) in patients with hemodialysis. This network meta-analysis aimed to systematically... (Meta-Analysis)
Meta-Analysis
Comparative efficacy of sodium thiosulfate, bisphosphonates, and cinacalcet for the treatment of vascular calcification in patients with haemodialysis: a systematic review and network meta-analysis.
BACKGROUND
Up to now, there is no unequivocal intervention to mitigate vascular calcification (VC) in patients with hemodialysis. This network meta-analysis aimed to systematically evaluate the clinical efficacy of sodium thiosulfate, bisphosphonates, and cinacalcet in treating vascular calcification.
METHODS
A comprehensive study search was performed using PubMed, Web of Science, the Cochrane Library, EMBASE and China National Knowledge Internet (CNKI) to collect randomized controlled trials (RCTs) of sodium thiosulfate, bisphosphonates, and cinacalcet for vascular calcification among hemodialysis patients. Then, network meta-analysis was conducted using Stata 17.0 software.
RESULTS
In total, eleven RCTs including 1083 patients were qualified for this meta-analysis. We found that cinacalcet (SMD - 0.59; 95% CI [-0.95, -0.24]) had significant benefit on vascular calcification compared with conventional therapy, while sodium thiosulfate or bisphosphonates did not show such efficiency. Furthermore, as for ranking the efficacy assessment, cinacalcet possessed the highest surface under the cumulative ranking curve (SUCRA) value (88.5%) of lessening vascular calcification and was superior to sodium thiosulfate (50.4%) and bisphosphonates (55.4%). Thus, above results suggested that cinacalcet might be the most promising drug for vascular calcification treatment in hemodialysis patients. Mechanistically, our findings illustrated that cinacalcet reduced serum calcium (SMD - 1.20; 95% CI [-2.08, - 0.33]) and showed the tendency in maintaining the balance of intact Parathyroid Hormone (iPTH) level.
CONCLUSIONS
This network meta-analysis indicated that cinacalcet appear to be more effective than sodium thiosulfate and bisphosphonates in mitigating vascular calcification through decreasing serum calcium and iPTH. And cinacalcet might be a reasonable option for hemodialysis patients with VC in clinical practice.
SYSTEMATIC REVIEW REGISTRATION
[ http://www.crd.york.ac.uk/PROSPERO ], identifier [CRD42022379965].
Topics: Humans; Diphosphonates; Cinacalcet; Network Meta-Analysis; Calcium; Vascular Calcification; Randomized Controlled Trials as Topic; Thiosulfates
PubMed: 38254024
DOI: 10.1186/s12882-024-03460-x -
Frontiers in Medicine 2022Lower extremity ulcers have significant morbidity, with treatment determined by the underlying disorder. Reported is a 32-year-old female presenting with small skin...
Lower extremity ulcers have significant morbidity, with treatment determined by the underlying disorder. Reported is a 32-year-old female presenting with small skin nodules and bruises across her legs 4 weeks following her second COVID vaccination. These lesions progressed into large, necrotic ulcers over several months. Initial work-up showed widespread pannicular thrombotic vasculopathy with ischemic skin necrosis. The tissue was negative for calcification on Von Kossa histochemistry, and a working diagnosis of subcutaneous thrombotic vasculopathy was suggested. The ulcers progressed despite treatments with corticosteroids, therapeutic anticoagulation, intravenous immunoglobulin, plasmapheresis, sodium thiosulfate, wound care, and repeat debridement. Later debridement specimens demonstrated rare vascular and pannicular calcifications. This finding supports the hypothesis that subcutaneous thrombotic vasculopathy is a precursor to calciphylaxis, the patient's current working diagnosis. However, based on the patient's entire clinical picture, a definitive diagnosis has yet to be found. This report highlights the challenges of working with rare diseases and the importance of multidisciplinary cooperation.
PubMed: 35492355
DOI: 10.3389/fmed.2022.843793 -
Journal of Veterinary Internal Medicine 2013Arsenic toxicosis is uncommon in cattle and successful treatment is rarely reported. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Arsenic toxicosis is uncommon in cattle and successful treatment is rarely reported.
OBJECTIVES
This analysis reviews all cases of acute arsenic toxicosis in cattle reported in the literature and describes cases from Purdue University that had a favorable outcome. Clinical presentation of the disease, treatments, and variables associated with survival are described.
ANIMALS
One hundred and fifty-six cattle with arsenic toxicosis from 16 outbreaks.
METHODS
Meta-analysis.
RESULTS
The most common clinical signs were sudden death (68%), diarrhea (33%), ataxia (29%), dehydration (22%), and respiratory distress (4%). The most common clinicopathologic abnormalities included azotemia (100%), hematuria (100%), increased liver enzyme activity (86%), and increased hematocrit (60%). One percent of cattle survived and the survival time for nonsurvivors ranged from 20 hours to 21 days. None of the clinical signs or clinicopathologic findings was associated with survival. Treatment was attempted in 24% of cases and was not associated with survival (P = .055), but administration of an antidote and administration of fluids were associated with better outcome (P = .036 and P = .009, respectively). In the animals presented to Purdue University, treatment with IV fluids and sodium thiosulfate resulted in decreased blood arsenic concentrations in all animals (P = .009) and a survival rate of 50%.
CONCLUSIONS AND CLINICAL IMPORTANCE
Although acute arsenic toxicosis has a poor prognosis, survival is possible if aggressive fluid therapy and antidotes are administered.
Topics: Animals; Arsenic Poisoning; Cattle; Cattle Diseases
PubMed: 23758199
DOI: 10.1111/jvim.12124 -
Antioxidants (Basel, Switzerland) Jan 2022Hypertension is highly prevalent in chronic kidney disease (CKD). Hydrogen sulfide (HS) is an endogenously produced gasotransmitter with vasodilator properties. We,...
Hypertension is highly prevalent in chronic kidney disease (CKD). Hydrogen sulfide (HS) is an endogenously produced gasotransmitter with vasodilator properties. We, hence, investigated whether oral administration of sodium thiosulfate (STS), a clinically applicable HS-based therapy, can exert a protective effect against hypertension in an adenine-induced CKD rat model. Eight-week-old male Sprague-Dawley rats were fed with 0.5% adenine chow for 3 weeks to induce CKD. After 1 week, the rats were divided into two groups: one without and one with STS (2 g/kg body weight/day) in drinking water for 2 weeks. Treatment with STS lowered systolic and diastolic blood pressure by 7 and 9 mm Hg, respectively. Renal HS-generating enzyme expression was inhibited by CKD, while STS therapy increased plasma levels of HS and thiosulfate. Additionally, restoration of nitric oxide bioavailability and rebalance of the renin-angiotensin system may contribute to the protective effects of STS. Our data suggest that the oral administration of STS improves hypertension in an adenine-induced CKD model, which brings us closer to the clinical translation of HS-targeting therapy in CKD-induced hypertension.
PubMed: 35052651
DOI: 10.3390/antiox11010147