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BACKGROUND: A dissolving agent for calcium hydroxylapatite (CaHA, Radiesse) soft-tissue filler would be of value should inadvertent intravascular injection, vascular compromise, nodule formation, or overcorrection occur. METHODS: In a prospective, single-center, proof-of-concept study, 12 cadaveric porcine skin samples were injected with CaHA (0.4–0.8 mL). Samples were then randomized to intralesional injection of 0.2-mL sodium thiosulfate (STS, 12.5 g/50 mL); 1 to 2 g of topical sodium metabisulfite (SMB, 25% SMB in 120-mL gel) applied with occlusion, or both intralesional STS and topical SMB. Control samples were not treated after CaHA injection. A 4-mm punch biopsy was obtained 24 hours after treatment, and tissue sections were stained with hematoxylin and eosin and prepared for light microscopy. A board-certified dermatopathologist estimated the amount of CaHA present in each sample. RESULTS: Intralesional STS alone or combined with topical SMB completely dissolved CaHA in the porcine skin samples. Topical SMB treatment reduced, but did not entirely clear CaHA from the tissue samples. The control samples contained easily identifiable CaHA microspheres. CONCLUSION: This proof-of-concept study illustrates the potential reversibility of CaHA filler with intralesional STS, topical SMB, and the combination of both agents. Larger, in vivo, studies are now warranted to provide further insight. [ABSTRACT FROM AUTHOR]

Background: Acute lung injury is characterized by neutrophilic inflammation and increased lung permeability. Thiosulfate is a stable metabolite of hydrogen sulfide, a gaseous mediator that exerts antiinflammatory effects. Although sodium thiosulfate (STS) has been used as an antidote, the effect of STS on acute lung injury is unknown. The authors assessed the effects of STS on mice lung and vascular endothelial cells subjected to acute inflammation.Methods: Lung injury was assessed in mice challenged with intratracheal lipopolysaccharide or subjected to cecal ligation and puncture with or without STS. Effects of STS on endothelial permeability and the production of inflammatory cytokines and reactive oxygen species were examined in cultured endothelial cells incubated with lipopolysaccharide or tumor necrosis factor-α. Levels of sulfide and sulfane sulfur were measured using novel fluorescence probes.Results: STS inhibited lipopolysaccharide-induced production of cytokines (interleukin-6 [pg/ml]; 313±164, lipopolysaccharide; 79±27, lipopolysaccharide+STS [n=10]), lung permeability, histologic lung injury, and nuclear factor-κB activation in the lung. STS also prevented up-regulation of interleukin-6 in the mouse lung subjected to cecal ligation and puncture. In endothelial cells, STS increased intracellular levels of sulfide and sulfane sulfur and inhibited lipopolysaccharide or tumor necrosis factor-α-induced production of cytokines and reactive oxygen species. The beneficial effects of STS were associated with attenuation of the lipopolysaccharide-induced nuclear factor-κB activation through the inhibition of tumor necrosis factor receptor-associated factor 6 ubiquitination.Conclusions: STS exerts robust antiinflammatory effects in mice lung and vascular endothelium. The results suggest a therapeutic potential of STS in acute lung injury. [ABSTRACT FROM AUTHOR]

B Learning Objectives: b Doxorubicin (DOX), a widely used anti-cancer agent, can cause cardiomyopathy dose-dependently. B Methods: b Male C57BL/6N mice were intraperitoneally administered a single dose (20 or 30 mg/kg) of DOX, followed by an injection of sodium thiosulfate (STS) (2 g/kg) 4 h later. However, injecting STS 4 h after DOX injection improved the survival (50%; p< 0.05) and suppressed the DOX-induced elevation of the CK and LDH levels in plasma, suggesting that STS protects the heart against DOX. [Extracted from the article]

The aim of this study was to investigate the effects of sodium thiosulfate (STS), glutathione (GSH), acetylcysteine (AC), and gemcitabine on the platinum-protein (Pt-protein) and platinum-DNA (Pt-DNA) binding of cisplatin in whole blood. This was done to obtain more insight into the platinum (Pt) binding in whole blood and the effects of modulators on this process. STS, GSH, AC, and gemcitabine were added before and after the incubation of whole blood with cisplatin. Pt levels in plasma and plasma ultrafiltrate and the Pt that is bound to DNA in peripheral blood mononuclear cells were determined using inductively coupled plasma mass spectrometry. Additionally, information on the major Pt-DNA adducts was obtained by separation of the Pt-DNA adducts by high performance liquid chromatography with off-line inductively coupled plasma mass spectrometry detection. Results showed that the reactive Pt levels in whole blood are reduced by STS, GSH, and AC. This reduction was demonstrated by a reduced Pt-protein and Pt-DNA binding in the presence of sulfur compounds. Furthermore, STS and AC seemed to be able to release Pt from proteins. The compounds could hardly release Pt from the DNA. Gemcitabine slightly inhibited Pt-DNA binding and did not alter Pt-protein binding. The type of Pt-DNA adducts found were not altered in the presence of the modulators. In conclusion, the results of this study illustrate that STS, GSH, and AC affect Pt binding in whole blood, which suggests that these compounds could affect Pt binding in patients. By interfering with Pt-DNA and Pt-protein binding, the compounds could influence side effects and cytotoxicity.

Unlabelled: A previous study reported that the co-infusion of IV sodium thiosulfate (STS) with sodium nitroprusside (SNP) to near-term gravid ewes prevented both maternal and fetal cyanide toxicity. We questioned whether maternally administered STS crossed the ovine placenta to enhance fetal transulfuration of cyanide, or whether the fetus was dependent on maternal detoxification of cyanide after diffusion of cyanide into the maternal circulation. Ten anesthetized, near-term gravid ewes underwent hysterotomies with delivery of fetal heads for venous catheterization. Five control ewes received IV isotonic sodium chloride solution, whereas five experimental ewes received IV STS (50 mg/kg over 15 min). Serial plasma thiosulfate concentrations in ewes and fetuses were measured over 135 min. Areas under the time-plasma thiosulfate concentration curves were calculated for experimental and control ewes at 2758+/-197 and 508+/-74 min x mg(-1) x L(-1), respectively (P < 0.008). Mean areas under the curve for experimental and control fetuses were 236+/-34 and 265+/-23 min x mg(-1) x L(-1), respectively (P > 0.5). Maternally administered STS may prevent fetal cyanide poisoning from SNP administration without relying on STS crossing the placenta into the fetal circulation. Fetal cyanide may cross down a concentration gradient from fetal to maternal circulation, to be transulfurated to thiocyanate in maternal tissues., Implications: We evaluated the mechanism of action of sodium thiosulfide (STS) in sodium nitroprusside-induced cyanide toxicity in the ewe. Fetal cyanide poisoning is alleviated by maternal administration of STS, although this cyanide antidote apparently does not cross the placenta.

We have previously reported that the thiol compound tiopronin protects rat kidneys in vitro against the toxic activity of cisplatin. The influence of tiopronin and sodium thiosulfate (STS) on the cytotoxicity of cisplatin has been investigated on P388 leukemic cells in vitro after 3 days. The combination has also been investigated in vivo in BDF1 mice bearing a P388 s.c. tumor. In contrast to STS, tiopronin did not significantly reduce the cytotoxic activity of cisplatin in vitro and nor did it affect the uptake of platinum (cisplatin-derived), binding to DNA or the percentage of interstrand cross-links (%ISCL) formation. The co-administration of cisplatin (4 mg/kg) and tiopronin (150 and 300 mg/kg) to BDF1 female mice bearing a s.c. P388 tumor produced a significant reduction in tumor growth similar to that of a single 6 mg/kg dose of cisplatin. Interestingly, pre-incubation in vitro of either tiopronin or STS for 2 h with the species formed from cisplatin by hydrolysis demonstrated their ability in inhibiting the cytotoxicity of these reactive platinum products. These results indicate that tiopronin does not reduce the cytotoxicity of cisplatin in vitro, as STS does. This may be, at least partly, because of a different effect of the two thiol compounds on the cellular uptake and binding of platinum to DNA. Notably, tiopronin substantially reduced tumor growth in mice treated with a non-toxic dose of cisplatin (p < or = 0.0277), suggesting some positive influence of this thiol compound on the antitumor properties of cisplatin. The ability of tiopronin to protect in vitro against the cytotoxicity of the aquation products of cisplatin may be related to its nephroprotective effect.