Pharmacokinetic Properties of Arsenic Species after Intravenous and Intragastrical Administration of Arsenic Trioxide Solution in Cynomolgus Macaques Using HPLC-ICP-MS

Shi, Qiaoli; Ju, Mingyan; Zhu, Xiaoxia; Gan, Hui; Gu, Ruixia; Wu, Zhuona; Zhang, Meng; Dou, Guifang

doi:10.3390/molecules24020241

Cited by 12 publications

(10 citation statements)

References 60 publications

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“…administration was 10 vs. 5 min, 0.22 ± 0.08 h vs. 0.13 ± 0.01 h, respectively. The absolute oral bioavailability of As III was approximately equal to 81.03%, which demonstrated the fact that orally administered ATO was well absorbed (Ravandi et al, 2020), and the results were higher than the results of the previous study (81.03 vs. 60.9%) (Shi et al, 2019). It is noteworthy that the C max of i.g.…”

Section: Discussionmentioning

confidence: 55%

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Pharmacokinetic Characteristics, Tissue Bioaccumulation and Toxicity Profiles of Oral Arsenic Trioxide in Rats: Implications for the Treatment and Risk Assessment of Acute Promyelocytic Leukemia

et al. 2021

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Oral arsenic trioxide (ATO) has demonstrated a favorable clinical efficiency in the treatment of acute promyelocytic leukemia (APL). However, the pharmacokinetic characteristics, tissue bioaccumulation, and toxicity profiles of arsenic metabolites in vivo following oral administration of ATO have not yet been characterized. The present study uses high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) to assess the pharmacokinetics of arsenic metabolites in rat plasma after oral and intravenous administration of 1 mg kg−1 ATO. In addition, the bioaccumulation of arsenic metabolites in blood and selected tissues were evaluated after 28 days oral administration of ATO in rats at a dose of 0, 2, 8, and 20 mg kg−1 d−1. The HPLC-HG-AFS analysis was complemented by a biochemical, hematological, and histopathological evaluation conducted upon completion of ATO treatment. Pharmacokinetic results showed that arsenite (AsIII) reached a maximum plasma concentration rapidly after initial dosing, and the absolute bioavailability of AsIII was 81.03%. Toxicological results showed that the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and white blood cells (WBC) in the 20 mg kg−1 d−1 ATO group were significantly increased compared to the control group (p < 0.05). The distribution trend of total arsenic in the rat was as follows: whole blood > kidney > liver > heart. Dimethylated arsenic (DMA) was the predominant bioaccumulative metabolite in the whole blood, liver, and heart, while monomethylated arsenic (MMA) was the predominant one in the kidney. Collectively, these results revealed that oral ATO was rapidly absorbed, well-tolerated, and showed organ-specific and dose-specific bioaccumulation of arsenic metabolites. The present study provides preliminary evidence for clinical applications and the long-term safety evaluation of oral ATO in the treatment of APL.

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Section: Discussionmentioning

confidence: 55%

“…treatment and risk assessment of ATO treatment (Shi et al, 2019;Ravandi et al, 2020). Furthermore, oral and i.v.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Characteristics, Tissue Bioaccumulation and Toxicity Profiles of Oral Arsenic Trioxide in Rats: Implications for the Treatment and Risk Assessment of Acute Promyelocytic Leukemia

et al. 2021

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“…The median lethal dose (LD 50 ) was calculated by the modulated Karber method while the silver ions accumulation in tissues was measured by the previously built ICP-MS method. 24 …”

Section: Resultsmentioning

confidence: 99%

“…After 7 days, mice were sacrificed, and residual silver ions in organs, including the brain, heart, spleen, liver, lung, and kidneys, were measured by inductively coupled plasma mass spectrometry (ICP-MS). 24 …”

Section: Methodsmentioning

confidence: 99%

Combined Silver Sulfadiazine Nanosuspension with Thermosensitive Hydrogel: An Effective Antibacterial Treatment for Wound Healing in an Animal Model

Liu¹,

Fan²,

Meng³

et al. 2023

IJN

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Introduction Silver sulfadiazine (AgSD) is widely used in burn wound treatment due to its broad-spectrum antibacterial activity. However, its application in wound healing is greatly hindered by the low solubility of AgSD particles and their cellular cytotoxicity. Herein, we studied the safety and in vivo efficacy of nano-sized silver sulfadiazine loaded in poloxamer thermosensitive hydrogel (NS/Gel). Methods In NS/Gel, silver sulfadiazine was prepared into silver sulfadiazine nanosuspension (NS) to improve the solubility and enhance its antibacterial activity, whereas the poloxamer thermosensitive hydrogel was selected as a drug carrier of NS to achieve slow drug release and reduced cytotoxicity. The acute toxicity of silver sulfadiazine nanosuspension was first evaluated in healthy mice, and its median lethal dose (LD 50 ) was calculated by the modified Karber method. Furthermore, in vivo antibacterial effect and wound healing property of NS/Gel were evaluated on the infected deep second-degree burn wound mice model. Results The mortality ratio of mice was concentration-dependent, and the LD 50 for silver sulfadiazine nanosuspension was estimated to be 252.1 mg/kg (230.8 to 275.4 mg/kg, 95% confidence limit). The in vivo dosages used for burn wound treatment (40–50 mg/kg) were far below LD 50 (252.1 mg/kg). NS/Gel significantly accelerated wound healing in the deep second wound infection mice model, achieving > 85% wound contraction on day 14. Staphylococcus aureus in the wound region was eradicated after 7 days in NS/Gel group, while the bacterial colony count was still measurable in the control group. Histological analysis and cytokines measurement confirmed that the mice treated with NS/Gel exhibited well-organized epithelium and multiple keratinized cell layers compared to control groups with the modulated expression of IL-6, VEGF, and TGF-β. Conclusion The combination of silver sulfadiazine nanosuspension and thermo-responsive hydrogel has great potential in clinical burn wound treatment.

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“…The authors identied one of the unknown peaks as an arsenosugar (2,3-dihydroxypropyl-5-deoxy-5(dimethylarsenoso)furanoside) using ESI-MS. 42 Shi et al used a Zorbax SB-Aq column with a mobile phase consisting of 20 mM citric acid and 5 mM sodium hexanesulfonate adjusted to a pH of 4.3 to achieve separation of As(III), As(V), MMA, and DMA in under 4 min. 43 2.2.3. Reversed-phase-liquid chromatography (RP-LC).…”

Section: Chromatographic Methods and Hyphenated Techniquesmentioning

confidence: 99%

Review of analytical techniques for arsenic detection and determination in drinking water

Bhat

Hara²,

Tian

et al. 2023

Environ. Sci.: Adv.

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Pharmacokinetic Properties of Arsenic Species after Intravenous and Intragastrical Administration of Arsenic Trioxide Solution in Cynomolgus Macaques Using HPLC-ICP-MS

Cited by 12 publications

References 60 publications

Pharmacokinetic Characteristics, Tissue Bioaccumulation and Toxicity Profiles of Oral Arsenic Trioxide in Rats: Implications for the Treatment and Risk Assessment of Acute Promyelocytic Leukemia

Pharmacokinetic Characteristics, Tissue Bioaccumulation and Toxicity Profiles of Oral Arsenic Trioxide in Rats: Implications for the Treatment and Risk Assessment of Acute Promyelocytic Leukemia

Combined Silver Sulfadiazine Nanosuspension with Thermosensitive Hydrogel: An Effective Antibacterial Treatment for Wound Healing in an Animal Model

Review of analytical techniques for arsenic detection and determination in drinking water

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