Kominox (sodium metaarsenite) / Komipharm - LARVOL DELTA

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, J Biochem Mol Toxicol) - "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."

Journal • Hepatology • CASP3 • CASP8 • CAT • NQO1

Novel phloretin-based combinations targeting glucose metabolism in hepatocellular carcinoma through GLUT2/PEPCK axis of action: in silico molecular modelling and in vivo studies. (PubMed, Med Oncol) - "We investigated novel anti-HCC treatments through either the simultaneous inhibition of glycolysis and gluconeogenesis by "phloretin" and "sodium meta-arsenite", respectively (Combination 1); or the concurrent inhibition of glycolysis and induction of gluconeogenesis by phloretin and dexamethasone, respectively, (combination 2). Biochemically, both combinations caused a significant reduction in ATP levels, ALT, and AST activity compared to the other groups. In conclusion, we propose two novel phloretin-based combinations that can be used in treating HCC through the regulation of glucose metabolism and ATP production."

Journal • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • BECN1 • CASP3 • CCND1 • KRT18

Alternations of Fertility Parameters by Graded Dose of Inorganic Arsenic in Adult Male White Pekin Ducks. (PubMed, Biol Trace Elem Res) - "The experimental groups were as follows: (T-1) basal diet along with normal drinking water (control group); (T-2 to T-4) basal diet along with As in the form of sodium-meta-arsenite at 7, 14, and 28 ppm of drinking water respectively...Besides that, there was upregulation of nuclear factor kappa B (NF-κB), heat shock proteins (Hsps) and pro-inflammatory cytokines like interlukin (IL) series, i.e., IL-2, IL-6, IL-18, IL-1β and tumor necrosis factor- α (TNF-α) levels, whereas anti-inflammatory parameters like IL-4 and IL-10 levels showed downregulation in testis of As-treated groups. Together, these findings provide deeper understandings of the roles played by oxidative stress, NF-κB and Hsps in the progression of testicular injury, which may help to explain how the As induced male sterility, in ducks, due to exposure."

Journal • Oncology • CAT • IL10 • IL18 • IL1B • IL2 • IL4 • IL6 • NFKB1 • NF-κβ • TNFA

Therapeutic effects of CoenzymeQ10, Biochanin A and Phloretin against arsenic and chromium induced oxidative stress in mouse (Mus musculus) brain. (PubMed, 3 Biotech) - "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."

Journal • Preclinical

Characterization of metabolic pathways for biosynthesis of the flavor compound 3-methylbutanal by Lactococcus lactis. (PubMed, J Dairy Sci) - "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."

Journal

Coenzyme Q protected against arsenite and enhanced the capacity of 2,3-dimercaptosuccinic acid to ameliorate arsenite-induced toxicity in mice. (PubMed, BMC Pharmacol Toxicol) - "Findings from this study demonstrate that CoQ and DMSA separately or in a combination, significantly protect against arsenic-driven toxicity in mice. It is evident that with further pre-clinical and clinical studies, an adjunct therapy that incorporates CoQ alongside DMSA may find applications in nullifying arsenic-driven toxicity."

Journal • Preclinical • Dyslipidemia • Immunology • Inflammation • Metabolic Disorders

Therapeutic effects of biochanin A, phloretin, and epigallocatechin-3-gallate in reducing oxidative stress in arsenic-intoxicated mice. (PubMed, Environ Sci Pollut Res Int) - "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."

Journal • CAT

Anti-Tumor Effects of Sodium Meta-Arsenite in Glioblastoma Cells with Higher Akt Activities. (PubMed, Int J Mol Sci) - "Finally, we illustrated in vivo anti-tumor effects of KML001 using an intracranial xenograft mouse model. These results suggest that KML001 could be an effective chemotherapeutic drug for the treatment of glioblastoma cancer patients with higher Akt activity and PTEN loss."

Journal • Breast Cancer • Glioblastoma • Oncology • Solid Tumor • PTEN

Telomeric injury by KML001 in human T cells induces mitochondrial dysfunction through the p53-PGC-1α pathway. (PubMed, Cell Death Dis) - "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."

Journal • Metabolic Disorders • Oncology • NRF1

Scanning laser optical tomography resolves developmental neurotoxic effects on pioneer neurons. (PubMed, Sci Rep) - "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."

Journal

Comparative efficacy of Nano and Bulk Monoisoamyl DMSA against arsenic-induced neurotoxicity in rats. (PubMed, Biomed Pharmacother) - "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."

Journal • Preclinical • CNS Disorders • Pain • CAT

Disruption of Telomere Integrity and DNA Repair Machineries by KML001 Induces T Cell Senescence, Apoptosis, and Cellular Dysfunctions. (PubMed, Front Immunol) - "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."

Journal • Ataxia • Human Immunodeficiency Virus • Immunology • Infectious Disease • Movement Disorders • Primary Immunodeficiency

Phase I clinical trial of KML001 monotherapy in patients with advanced solid tumors. (PubMed, Expert Opin Investig Drugs) - "Doses equal to or greater than 10 mg/day KML001 alone were tolerable and produced plasma concentrations higher than biologically relevant targets."

Clinical • Journal • Monotherapy • P1 data • Hematological Disorders • Neutropenia • Oncology • Solid Tumor

0805 GCC: Trial Of Cisplatin And KML-001 in Platinum Responsive Malignancies (clinicaltrials.gov) - P1; N=23; Terminated; Sponsor: University of Maryland, Baltimore; N=15 ➔ 23; Recruiting ➔ Terminated; Toxicity was not felt to be acceptable for further development.

Enrollment change • Trial termination

Hormetic Dose Response of NaAsO on Cell Proliferation of Prostate Cells in Vitro: Implications for Prostate Cancer Initiation and Therapy. (PubMed, Dose Response) - "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."

Journal • Preclinical

KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study. (PubMed, Hepatobiliary Pancreat Dis Int) - "KML001 did not have enough anticancer effect on patients with advanced BTC resistant to gemcitabine. However, KML001 was safe and well-tolerable in terms of AEs and pain control when used as salvage therapy. Further studies are needed to establish arsenic agents as a reliable treatment option in patients with BTC."

Clinical • Journal