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Journal: Attenuation of chromium (VI) and arsenic (III)-induced oxidative stress and hepatic apoptosis by phloretin, biochanin-A, and coenzyme Q10 via activation of SIRT1/Nrf2/HO-1/NQO1 signaling. (Pubmed Central) - Aug 23, 2024
Potassium dichromate (75?ppm) and sodium meta-arsenite (100?ppm) were given in the drinking water to induce hepatotoxicity, conjugated with PHL and BCA (50?mg/kg each), and CoQ10 (10?mg/kg) intraperitoneally for 2 weeks...These findings highlight the crucial role of the PHL, BCA, and CoQ10 combination in reducing Cr and As-induced hepatotoxicity in mice. By averting the triggered apoptosis in conjunction with oxidative stress, this combination increases the SIRT1, Nrf2, HO-1, and NQO1 signaling, thereby reassuringly maintaining the cellular equilibrium.
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Preclinical, Journal: Therapeutic effects of CoenzymeQ10, Biochanin A and Phloretin against arsenic and chromium induced oxidative stress in mouse (Mus musculus) brain. (Pubmed Central) - May 14, 2022
Sodium meta-arsenite (100 ppm) and potassium dichromate (75 ppm) were given orally in conjugation with CoQ10 (10 mg/kg), BCA & PHL (50 mg/kg each) in accordance with body weight per day for the 2 weeks experimental duration...The administration of CoQ10, BCA, and PHL ameliorated the effects of arsenic and chromium induced oxidative stress in the exposed mice. Our research unfolds the remedial outcome of these natural compounds contrary to the combined arsenic and chromium associated-neurotoxicity in the experimental model.
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Journal: Characterization of metabolic pathways for biosynthesis of the flavor compound 3-methylbutanal by Lactococcus lactis. (Pubmed Central) - Dec 29, 2021
Furthermore, the results of a sodium meta-arsenite inhibition experiment showed that the 3-methylbutanal-producing capacities of each strain declined to various degrees...As a result, these L. lactis strains were divided into 3 categories according to gene diversity, gene expression, and 3-methylbutanal production. The results of this study refine our knowledge of the genetic determinants of 3-methylbutanal biosynthesis in L. lactis and explain the effect of both synthesis pathways on 3-methylbutanal production.
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Preclinical, Journal: Therapeutic effects of biochanin A, phloretin, and epigallocatechin-3-gallate in reducing oxidative stress in arsenic-intoxicated mice. (Pubmed Central) - May 8, 2021
For this purpose, mice were orally treated with sodium meta-arsenite (20 mg/kg bw/day), along with co-administration of BCA (50 mg/kg bw/day), phloretin (50 mg/kg bw/day), and EGCG (40 mg/kg bw/day) for the 2-week duration...The administration of BCA, phloretin, and EGCG, in a major way, reversed the alterations in the abovementioned parameters in the arsenic-intoxicated mice. Our findings revealed the beneficial effects of the flavonoids against the arsenic-induced toxicity, due to their ability to enhance the intracellular antioxidant response system by modulating the Nrf2 signaling pathway.
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Journal: Telomeric injury by KML001 in human T cells induces mitochondrial dysfunction through the p53-PGC-1α pathway. (Pubmed Central) - Apr 10, 2021
These results, forging a direct link between telomeric and mitochondrial biology, shed new light on the human T cell aging network, and demonstrate that the p53-PGC-1α-NRF-1 axis contributes to mitochondrial dysfunction in the setting of telomeric DDR. This study suggests that targeting this axis may offer an alternative, novel approach to prevent telomere damage-mediated mitochondrial and T cell dysfunctions to combat a wide range of immune aging-associated human diseases.
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Preclinical, Journal: Comparative efficacy of Nano and Bulk Monoisoamyl DMSA against arsenic-induced neurotoxicity in rats. (Pubmed Central) - Feb 26, 2021
An in vivo study was planned to investigate the therapeutic efficacy of MiADMSA-encapsulated solid lipid nanoparticles (Nano-MiADMSA; 50 mg/kg orally for 5 days) and compared it with bulk MiADMSA against sodium meta-arsenite exposed rats (25 ppm in drinking water, for 12 weeks) in male rats...Recoveries in neurobehavioral parameters further confirmed nano-MiADMSA to be more effective than bulk MiADMSA. We conclude that treatment with Nano-MiADMSA is a better therapeutic strategy than bulk MiADMSA in reducing the effects of arsenic-induced oxidative stress and associated neurobehavioral changes.
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Clinical, P1 data, Journal, Monotherapy: Phase I clinical trial of KML001 monotherapy in patients with advanced solid tumors. (Pubmed Central) - Feb 3, 2021
We conclude that treatment with Nano-MiADMSA is a better therapeutic strategy than bulk MiADMSA in reducing the effects of arsenic-induced oxidative stress and associated neurobehavioral changes. Doses equal to or greater than 10 mg/day KML001 alone were tolerable and produced plasma concentrations higher than biologically relevant targets.
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Journal: Scanning laser optical tomography resolves developmental neurotoxic effects on pioneer neurons. (Pubmed Central) - Nov 19, 2020
The defects in axon elongation and pathfinding of pioneer axons caused by two DNT-positive reference compounds (methylmercury chloride; sodium(meta)arsenite) are compared to the biochemically measured general viability of the embryo. Using conventional fluorescence microscopy to establish concentration-response curves of axon elongation, we show that this assay identifies methylmercury chloride and the pro-apoptotic compound staurosporine as developmental neurotoxicants.
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Journal: Disruption of Telomere Integrity and DNA Repair Machineries by KML001 Induces T Cell Senescence, Apoptosis, and Cellular Dysfunctions. (Pubmed Central) - Aug 27, 2020
Importantly, these KML001-induced telomeric DNA damage and T cell senescent phenotype and machineries recapitulated our findings in patients with clinical HCV or HIV infection in that their T cells were also senescent with short telomeres and thus more vulnerable to KML001-induced apoptosis. These results shed new insights on the T cell aging network that is critical and essential in protecting chromosomal telomeres from unwanted DNA damage and securing T cell survival during cell crisis upon genomic insult.
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Enrollment change, Trial termination, Metastases: 0805 GCC: Trial Of Cisplatin And KML-001 in Platinum Responsive Malignancies (clinicaltrials.gov) - Mar 17, 2020
P1, N=23, Terminated,
These results shed new insights on the T cell aging network that is critical and essential in protecting chromosomal telomeres from unwanted DNA damage and securing T cell survival during cell crisis upon genomic insult. N=15 --> 23 | Recruiting --> Terminated; Toxicity was not felt to be acceptable for further development.
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Preclinical, Journal: Hormetic Dose Response of NaAsO on Cell Proliferation of Prostate Cells in Vitro: Implications for Prostate Cancer Initiation and Therapy. (Pubmed Central) - May 9, 2019
Sodium meta-arsenite (NaAsO) has been suggested to play a role both in initiation/progression of prostate cancer and as a future antiprostate cancer drug...We conclude that NaAsO is able to increase cell proliferation of prostate cells in vitro at low concentrations, while it decreases cell viability at high concentrations. This novel finding has to be further addressed if NaAsO should be developed into an antiprostate cancer drug.
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Preclinical, Journal: Effects of arsenic and lead combined exposure on brain monoaminergic system and behavioral functions in rats: Reversal effect of MiADMSA. (Pubmed Central) - Apr 18, 2019
...Pregnant rats were exposed to sodium metaarsenite (50 ppm) and lead acetate (0.2%) individually and in combination (As = 25 ppm + Pb = 0.1%) via drinking water from gestation day (GD) 6 to postnatal day (PND) 21...However, MiADMSA administration showed reversal effects against the As- and/or Pb-induced impairments in the monoaminergic system as well as in behavioral functions of rats. Our data demonstrated that the mixture of Pb and As induced synergistic toxicity to developing brain leading to impairments in neurobehavioral functions and also suggest therapeutic efficacy of MiADMSA against Pb- and/or As-induced developmental neurotoxicity.
- |||||||||| Kominox (sodium metaarsenite) / Komipharm
Trial primary completion date, Metastases: 0805 GCC: Trial Of Cisplatin And KML-001 in Platinum Responsive Malignancies (clinicaltrials.gov) - Feb 26, 2015
P1, N=15, Recruiting,
Our data demonstrated that the mixture of Pb and As induced synergistic toxicity to developing brain leading to impairments in neurobehavioral functions and also suggest therapeutic efficacy of MiADMSA against Pb- and/or As-induced developmental neurotoxicity. Trial primary completion date: Dec 2012 --> Jun 2015
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