Comparative assessment of the effects of meso-2,3-dimercaptosuccinic acid and salinomycin on spleen function of cadmium-exposed mice

Kamenova, Kalina; Gluhcheva, Yordanka; Dorkov, Petar; Ivanova, Juliana

doi:10.1007/s11356-019-06473-4

Cited by 8 publications

(4 citation statements)

References 32 publications

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“…47 Dimercaprol (British Anti-Lewisite, BAL) and its analogues meso-2, 3-dimercaptosuccinic acid (DMSA) are also used as antidotes for heavy metal poisoning. 48 In contrast, BAL may increase burdens of kidney and liver, decrease the level of patients' survival and even enhance nephrotoxicity. 49 A randomized trial, in which 396 children were given DMSA at the dose of 1,050 mg/ body surface area (m 2 )/day for 7 days, showed that DMSA did not lower blood Cd in children with background exposure.…”

Section: Discussionmentioning

confidence: 99%

Renal glucose transporters play a role in removal of cadmium from kidney cells mediated by GMDTC – A novel metal chelator

et al. 2023

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Cadmium (Cd) is a toxic heavy metal, exposure to which leads to adverse health effects including chronic kidney damage. Tremendous efforts have been explored in identifying safe chelating agents for removing accumulated Cd from kidney, but with limited success owing to their associated side effects and the ineffectiveness in eliminating Cd. A newly developed chelating agent, sodium (S)-2-(dithiocarboxylato((2S,3 R,4R,5 R)-2,3,4,5,6-pentahydroxyhexyl) amino)-4(methylthio)butanoate (GMDTC), has been shown to effectively mobilize Cd from kidney. However, the mechanism(s) of removal are unclear, while it has been hypothesized that renal glucose transporters potentially play key roles mainly because GMDTC contains an open chain glucose moiety. To test this hypothesis, we utilized the CRISPR/Cas9 technology and human kidney tubule HK-2 cells, and constructed sodium-dependent glucose transporter 2 ( SGLT2) or glucose transporter 2 ( GLUT2) gene knockout cell lines. Our data showed that GMDTC’s ability in removing Cd from HK-2 cells was significantly reduced both in GLUT2 −/− or SGLT2 −/− cells, with a removal ratio reduced from 28.28% in the parental HK-2 cells to 7.37% in GLUT2 −/− cells and 14.6% in SGLT2 −/− cells. Similarly, knocking out the GLUT2 or SGLT2 led to a compromised protective effect of GMDTC in reducing cytotoxicity of HK-2 cells. This observation was further observed in animal studies, in which the inhibition of GLUT2 transporter by phloretin treatment resulted in reduced efficiency of GMDTC in removing Cd from the kidney. Altogether, our results show that GMDTC is safe and highly efficient in removing Cd from the cells, and this effect is mediated by renal glucose transporters.

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Section: Discussionmentioning

confidence: 99%

Renal glucose transporters play a role in removal of cadmium from kidney cells mediated by GMDTC – A novel metal chelator

et al. 2023

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“…Traditional chelating agents such as meso-2,3-dimercaptosuccinic acid (DMSA), dimercaprol (BAL), and ethylenediaminetetraacetic acid disodium (EDTA-2Na) have shown limited effectiveness in treating chronic Cd poisoning. They may even worsen Cd accumulation in the kidneys [ 26 , 28 , 29 , 30 , 31 ]. Several researchers have investigated natural compounds, such as curcumin and melatonin, and elements, such as zinc and selenium [ 32 , 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Anthocyanins from Lycium ruthenicum Murray Mitigate Cadmium-Induced Oxidative Stress and Testicular Toxicity by Activating the Keap1/Nrf2 Signaling Pathway

Dong,

Lu,

Xue

et al. 2024

Pharmaceuticals

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Cadmium (Cd) is a hazardous heavy metal environmental pollutant that has carcinogenic, teratogenic, and mutagenic properties. Excessive exposure to Cd can induce oxidative stress, which greatly harms the male reproductive system. Anthocyanins have remarkable antioxidative, anti-inflammatory, and anti-stress properties. In this study, we investigated the effects of anthocyanins and the underlying mechanisms through which anthocyanins mitigate Cd-induced reproductive damage. We isolated and purified Lycium ruthenicum Murray anthocyanin extract (LAE) and performed UHPLC-MS/MS to identify 30 different anthocyanins. We established an ICR mouse Cd injury model by administering 5 mg/kg/day CdCl2 for 28 consecutive days. LAE at 500 mg/kg/day effectively ameliorated testicular damage and preserved spermatogenesis. The mice in the LAE-treated group had elevated testosterone and inhibin B levels. Additionally, the treatment restored the activity of antioxidant enzymes, including T-SOD, CAT, and GR, and substantially increased the levels of the non-enzymatic antioxidant GSH. Research findings indicate that LAE can activate the SIRT1/Nrf2/Keap1 antioxidant pathway. This activation is achieved through the upregulation of both the SIRT1 gene and protein levels, leading to the deacetylation of Nrf2. Moreover, LAE reduces the expression of Keap1, alleviating its inhibitory effect on Nrf2. This, in turn, facilitates the uncoupling process, promoting the translocation of Nrf2 to the nucleus, where it governs downstream expression, including that of HO-1 and GPX1. LAE effectively mitigated toxicity to the reproductive system associated with exposure to the heavy metal Cd by alleviating oxidative stress in the testes.

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“…Salinomycin is originally applied as an antibacterial and anticoccidial drug, which is commercially used as a coccidiostat for poultry 26,27 . The potential antidote activity of salinomycin has also been documented from murine experiment results 28,29 . Several studies have further revealed that salinomycin could be an attractive drug candidate against viruses, for example, it is repurposed recently as a potential anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) agent 30 .…”

Section: Introduction—cancer Stem Cells (Cscs) and Salinomycinmentioning

confidence: 99%

“… 26 , 27 The potential antidote activity of salinomycin has also been documented from murine experiment results. 28 , 29 Several studies have further revealed that salinomycin could be an attractive drug candidate against viruses, for example, it is repurposed recently as a potential anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) agent. 30 The mechanism of action (MoA) of salinomycin against microbes is likely because of its ionophoric nature.…”

Section: Introduction—cancer Stem Cells (Cscs) and Salinomycinmentioning

confidence: 99%

Salinomycin as a potent anticancer stem cell agent: State of the art and future directions

Liu

et al. 2021

Medicinal Research Reviews

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Comparative assessment of the effects of meso-2,3-dimercaptosuccinic acid and salinomycin on spleen function of cadmium-exposed mice

Cited by 8 publications

References 32 publications

Renal glucose transporters play a role in removal of cadmium from kidney cells mediated by GMDTC – A novel metal chelator

Renal glucose transporters play a role in removal of cadmium from kidney cells mediated by GMDTC – A novel metal chelator

Anthocyanins from Lycium ruthenicum Murray Mitigate Cadmium-Induced Oxidative Stress and Testicular Toxicity by Activating the Keap1/Nrf2 Signaling Pathway

Salinomycin as a potent anticancer stem cell agent: State of the art and future directions

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