Antimonium Tartaricum as a Possible Homeopathic Prophylactic Remedy in the COVID-19 Epidemic.

The current COVID-19 (coronavirus disease 2019) epidemic has proved challenging due to its high impact on physical and mental health. According to Hahnemann, the founder of homeopathy, in an epidemic the most severe symptoms of the clinical condition presented by the population in question should be the basis for selecting the medication that is as similar as possible to them, and which should be administered to individuals who have been exposed to the disease but have not yet developed it. This medicine is called the genus epidemicus. This study aims to demonstrate the reasoning used to propose the homeopathic medicine Antimonium tartaricum (Ant-t) as a genus epidemicus in the COVID-19 epidemic. It was decided to develop the reasoning based on the respiratory symptoms described in the epidemiological bulletins presented by the Health Surveillance Secretariat of the Ministry of Health of Brazil, as these symptoms are the most serious of the disease. After repertorization, it was confirmed in the Materia Medica that Ant-t has a high degree of similarity with these respiratory symptoms, including the most serious situations, of COVID-19. Homeopathic Ant-t is thus a possible prophylactic genus epidemicus in the COVID-19 epidemic; further studies are needed to test this conclusion.

Behavior of two Leishmania infantum strains-evaluation of susceptibility to antimonials and expression of microRNAs in experimentally infected J774 macrophages and in BALB/c mice.

Strains of the same Leishmania parasite species, isolated from different host organisms, may exhibit unique infection profiles and induce a change in the expression of microRNAs among host macrophages and in model host mice. MicroRNAs (MiR) are endogenous molecules of about 22 nucleotides that are involved in many regulatory processes, including the vertebrate host immune response. In this respect, the infectivity and susceptibility to antimonials of two L. infantum strains, BH46, isolated from human, and OP46, isolated from symptomatic dog, were characterized in J774 macrophages and BALB/c mice. Parasite burden was assessed in the liver, spleen, and bone marrow using the serial limiting dilution technique. A higher parasite burden was observed in the spleen and bone marrow of animals infected with OP46 compared to BH46 strain. Our results also showed that OP46 was less susceptible to the antimonials. In addition, miR-122 and miR-155 expression was evaluated in the liver and J774 macrophages, and in spleens from infected animals, respectively. An increase was observed in the expression of miR-155 in J774 macrophages infected with both strains compared to uninfected cells, with a higher expression in cells infected with OP46. However, no difference in the expression of miR-122 and miR-155 was observed in the infected animals. Thus, this study shows that OP46 was more infective for mice, it caused a higher increase in miR-155 expression in infected macrophages and was less susceptible to the antimonials evaluated. These data suggest that alteration in miR-155 level likely plays a role in regulating the response to L. infantum.

Identification of cisplatin sensitizers through high-throughput combinatorial screening.

cis-Diamminedichloroplatinum/cisplatin (CDDP) is a major drug used in cancer chemotherapy; however, the toxic side-effects and development of drug resistance represent major challenges to the clinical use of CDDP. The aim of the present study was to identify effective drug combination regimens through high-throughput drug screening that can enhance the efficacy of CDDP, and to investigate the underlying mechanisms. A cell-based high-throughput screening methodology was implemented, using a library of 1,280 Food and Drug Administration (FDA)-approved drugs, to identify clinical compounds that act synergistically with CDDP. Our study identified two compounds, namely potassium antimony tartrate and topotecan, that significantly enhanced the sensitivity of colorectal and non-small cell lung cancer cells to CDDP. The synergistic action of both compounds with CDDP was confirmed by further quantitative analyses. Topotecan is a topoisomerase-1 inhibitor that has previously been shown to enhance the clinical response and overall patient survival when combined with CDDP by a yet unclear mechanism. We demonstrated that the combination of topotecan with CDDP significantly inhibited colony formation ability and increased the apoptosis of several cancer cell lines. Mechanistic analyses revealed that topotecan enhanced CDDP-induced DNA damage and inhibited the repair of DNA strand breaks, without affecting the cellular platinum content. Overall, the findings of this study demonstrated that the use of the FDA-approved drug panel in high-throughput screening is an effective method for identifying effective therapeutic regimens that are clinically relevant, and may have high feasibility for translation into clinical practice.

The antiparasitic drug, potassium antimony tartrate, inhibits tumor angiogenesis and tumor growth in nonsmall-cell lung cancer.

Repurposing existing drugs not only accelerates drug discovery but rapidly advances clinical therapeutic strategies. In this article, we identified potassium antimonyl tartrate (PAT), an antiparasitic drug, as a novel agent to block angiogenesis by screening US Food and Drug Administration-approved chemical drugs. By comparing the cytotoxicity of PAT in various nonsmall-cell lung cancer (NSCLC) cells with that observed in primary cultured human umbilical vein endothelial cells (HUVECs), we found that HUVECs were much more sensitive to the PAT treatment. In in vivo tumor xenograft mouse models established either by PAT-resistant A549 cells or by patient primary tumors, PAT significantly decreased the tumor volume and tumor weight of NSCLC xenografts at dosage of 40 mg/kg (i.p., daily) and, more importantly, augmented the antitumor efficacy of cisplatin chemotherapy. Remarkable loss of vascularization in the treated xenografts indicated the in vivo antiangiogenesis property of PAT, which was well correlated with its tumor growth inhibition in NSCLC cells. Furthermore, in the in vitro angiogenic assays, PAT exhibited dose-dependent inhibition of HUVEC proliferation, migration, and tube formation in response to different stimuli. Consistently, PAT also abolished the vascular endothelial cell growth factor-induced angiogenesis in the Matrigel plugs assay. Mechanistically, we found that PAT inhibited the activities of several receptor tyrosine kinases and specifically blocked the activation of downstream Src and focal adhesion kinases in HUVECs. Taken together, our results characterized the novel antiangiogenic and antitumor function of PAT in NSCLC cells. Further study of PAT in anticancer clinical trials may be warranted.

Enhanced schistosomicidal efficacy of tartar emetic encapsulated in pegylated liposomes.

The aim of the present study was to evaluate the ability of liposomes to improve the efficacy of tartar emetic (TA) against established Schistosoma mansoni infection. TA was used as a schistosomicidal drug model and both conventional liposomes (CL) and long-circulating pegylated liposomes (LCL) were evaluated. In the first experiment, TA, either free or encapsulated within CL or LCL, was given intraperitoneally (i.p.) as a single dose of 11 mg Sb/kg to mice experimentally infected with S. mansoni. Only the group treated with LCL showed a significant (55%) reduction in the worm burden, compared to the control groups (untreated or treated with empty LCL). In the second experiment, the efficacy of TA-containing LCL was evaluated at a higher dose (27 mg Sb/kg) by both subcutaneous (s.c.) and i.p. routes. Reduction levels of 67 and 82% were achieved by s.c. and i.p. routes, respectively. Strikingly, all mice survived to this high dose of antimony. This is in contrast with free TA that was lethal in 100% of mice at the same dose. The present work demonstrates that LCL reduce the acute toxicity of TA and effectively deliver this drug to S. mansoni during the late stages of parasite infection.

Potassium antimonyl tartrate induces caspase- and reactive oxygen species-dependent apoptosis in lymphoid tumoral cells.

The metalloid salt potassium antimonyl tartrate (PAT), previously used as an antiparasitic agent, has recently been shown to exert cytotoxicity towards acute promyelocytic leukaemia cells like arsenical compounds. In this study, we have investigated its effects towards human lymphoid malignant cells and compared them with those of arsenic trioxide (As2O3). Like As2O3, PAT was found to inhibit cell growth of various lymphoid cell lines, deriving from either acute lymphoid leukaemias (Jurkat, Molt-4 and Nalm-6) or lymphomas (Daudi, Raji and Rec1). PAT toxicity was linked, at least in part, to induction of apoptosis in both Daudi and Jurkat cells, which was dependent on caspase activity. This apoptotic process was also associated, similarly to that triggered by As2O3, with loss of mitochondrial potential and enhanced cellular production of reactive oxygen-related species. It was enhanced by co-treatment with the pro-oxidant buthionine sulphoximine and abolished in response to the antioxidant N-acetylcysteine, thus underlining that PAT toxicity, similarly to that of As2O3, is probably modulated by the redox status of the cells. PAT, used at concentrations in the micromolar range that are thought to be clinically achievable, was also demonstrated to markedly decrease the viability of primary cultured tumoral B cells that originated from 18 patients suffering from chronic lymphoid leukaemia whereas normal lymphocytes were less sensitive. These data therefore suggest that PAT may deserve to be evaluated in the treatment of some lymphoid malignancies.

Schistosoma mansoni: chemotherapy of infections of different ages.

Mice were treated with potassium antimony tartrate, hycanthone, oxamniquine, niridazole, or praziquantel at different times after infection with Schistosoma mansoni. The rate of cure was assessed by perfusion of surviving worms approximately 4 weeks after treatment, and the percentage reduction in worm burden was estimated relative to the number of adult worms perfused from control mice, comparably infected but untreated. All six drugs were relatively inactive against S. mansoni between 3 and 4 weeks after infection when compared with treatment at 5 to 6 weeks. However, the drugs differed in the patterns of cure they achieved in the 2-week period after administration of cercariae and in the period around the onset of patency. Worms that had been subjected to amoscanate or hycanthone in the third week after infection showed evidence of this as adults in having a reduced fecundity. Factors such as worm or host physiology, or host immune status may have had roles in the outcome of chemotherapy at different stages of maturation of S. mansoni.

The immunological aspects of praziquantel in unsensitized mice with experimentally induced schistosome pulmonary granuloma.

The effects of praziquantel on cellular and humoral immune responses were studied in Swiss Albino mice and compared with the effects of potassium antimony tartrate. The experimental animals were antigenically primed by intravenous injection of Schistosoma mansoni eggs; the test drugs were given one day before egg injection and their effects monitored 16 days later. The size of the experimentally-induced pulmonary granulomata, immediate and delayed antigen-induced foot pad swelling, in vitro macrophage migration inhibition and the percentage of lymphocytes forming antibody and complement-dependent rosettes with erythrocytes (% EAC-R) were parameters used to assess the effect of the drugs. Praziquantel suppressed the size of pulmonary granulomata and the immediate and delayed foot pad reaction. Macrophage migration inhibition and the percentage of lymphocytes forming EAC-rosettes were not significantly affected. Tartar emetic was more effective as an immunosuppressant drug in these tests than praziquantel.

Factors affecting the acquisition of resistance against Schistosoma mansoni in the mouse. V. Reduction in the degree of resistance to reinfection after chemotherapeutic elimination of recently patent primary infections.

Effective treatment of mice with six to eight week-old patent S. mansoni infections with any one of five schistosomicidal agents (Oxamniquine, Praziquantel, potassium antimony tartrate, Niridazole and Hycanthone) resulted in a reduction in the degree of resistance to homologous challenge in the treated animals when compared with the level of resistance to reinfection observed in untreated mice with intact primary infections. Mice challenged five to six weeks after treatment with Praziquantel, Niridazole or Hycanthone demonstrated a lower level of resistance than mice challenged within 10 days of the termination of the chemotherapeutic schedules. Direct comparison of Praziquantel with potassium antimony tartrate indicated that treatment with the former drug allowed retention of a greater level of acquired resistance than the antimonial in the immediate post-treatment period. Resistance to reinfection in Hycanthone-treated mice was not restored by intravenous injection of S. mansoni eggs before challenge.

The immune-dependence of schistosomicidal chemotherapy: relative lack of efficacy of an antimonial in Schistosoma mansoni-infected mice deprived of their T-cells and the demonstration of drug-antiserum synergy.

When T-cell deprived CBA mice, infected with Schistosoma mansoni, were treated orally with potassium antimony tartrate, the reduction in size of their worm burdens was less than in similarly treated, immunologically-intact animals. The defect in deprived mice could be restored by the administration of serum obtained from S. mansoni-infected normal mice simultaneously with the drug, but by a different route. A serum component, probably immunoglobulin, obtained from rabbits which had been injected with an extract from S. mansoni adult worms was also found to act synergystically with the antimonial in the chemotherapeutic eradication of S. mansoni worms from immunologically intact mice.

Left ventricular dysfunction after intravenous tartar emetic.

Left ventricular dysfunction had been reported in many patients suffering from schistosomal cor pulmonale. The nocuous agents affecting the left ventricle have not been defined. Antischistosomal therapy is suspected to contribute in the adverse effects on the myocardium, particularly antimonials and niridazole. In this study, the left ventricular performance was studied in 29 patients suffering from schistosomiasis before and 30 min after i.v. therapeutic dose of a tartar emetic. After the injection, the PEPI and PEPI/LVETI were increased, the LVETI was abbreviated, EF. was reduced, the LVEDP was raised, the peak dp/dt and the Vmax were reduced. Toxic effects of the T.E. on the myocardium and diminished contractility of the left ventricle were presumed to be caused by T.E. Other factors adversely affecting the myocardium in patients suffering from schistosomiasis cannot be excluded.