In vivo evidence of the role of Vidatox on tumor proliferation. (a) Growth curve, considering all lesions detected by imaging, showed a strong effect on nodules growth by Vidatox after 30 days of administration when compared with control. **P < 0.01 (by two tailed Student's t test). Moreover 15 days of sorafenib treatment significantly reduced tumor proliferation p < 0.05 (by two tailed Student's t test) compared to both control and Vidatox rats. (b) Quantification of growth fraction measured by Ki-67 staining in control an in Vidatox treated rat HCCs. (c) Immunohistochemistry analysis in four representative HCC cases of control, sorafenib and Vidatox treated rats showing Ki-67 expression. Scale bars = 50 μ m. Ki-67 expression in HCCs of sorafenib treated rats was shown to appreciate the efficacy of sorafenib on cell proliferation. 

In vivo evidence of the role of Vidatox on tumor proliferation. (a) Growth curve, considering all lesions detected by imaging, showed a strong effect on nodules growth by Vidatox after 30 days of administration when compared with control. **P < 0.01 (by two tailed Student's t test). Moreover 15 days of sorafenib treatment significantly reduced tumor proliferation p < 0.05 (by two tailed Student's t test) compared to both control and Vidatox rats. (b) Quantification of growth fraction measured by Ki-67 staining in control an in Vidatox treated rat HCCs. (c) Immunohistochemistry analysis in four representative HCC cases of control, sorafenib and Vidatox treated rats showing Ki-67 expression. Scale bars = 50 μ m. Ki-67 expression in HCCs of sorafenib treated rats was shown to appreciate the efficacy of sorafenib on cell proliferation. 

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Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate...

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... line with the above observations in rats with HCC the treatment with Vidatox for 30 days increased tumor growth significantly more than in control rats (p = 0.01) ( Fig. 2A). Indeed, HCCs proliferation was higher in rats treated with Vidatox than in control rats, as shown by immuno-staining for Ki-67 (Fig. 2B,C). Contrary, after 15 days of sorafenib exposure rat HCCs showed a much lower proliferation compared to vehicle ( Fig. 2A-C). Macroscopically the rats treated with Vidatox showed a greater degeneration of the liver, a greater number of HCC nodules and larger (Fig. 3A). According to in vitro results in HepG2 and Snu449 cells, in the invasive edge of Vidatox treated HCCs there are more cells that penetrate the non-tumor liver tissue surrounding the HCC nodule (Fig. ...
Context 2
... line with the above observations in rats with HCC the treatment with Vidatox for 30 days increased tumor growth significantly more than in control rats (p = 0.01) ( Fig. 2A). Indeed, HCCs proliferation was higher in rats treated with Vidatox than in control rats, as shown by immuno-staining for Ki-67 (Fig. 2B,C). Contrary, after 15 days of sorafenib exposure rat HCCs showed a much lower proliferation compared to vehicle ( Fig. 2A-C). Macroscopically the rats treated with Vidatox showed a greater degeneration of the liver, a greater number of HCC nodules and larger (Fig. 3A). According to in vitro results in HepG2 and Snu449 cells, in the invasive edge of Vidatox treated HCCs there are more cells that penetrate the non-tumor liver tissue surrounding the HCC nodule (Fig. ...
Context 3
... line with the above observations in rats with HCC the treatment with Vidatox for 30 days increased tumor growth significantly more than in control rats (p = 0.01) ( Fig. 2A). Indeed, HCCs proliferation was higher in rats treated with Vidatox than in control rats, as shown by immuno-staining for Ki-67 (Fig. 2B,C). Contrary, after 15 days of sorafenib exposure rat HCCs showed a much lower proliferation compared to vehicle ( Fig. 2A-C). Macroscopically the rats treated with Vidatox showed a greater degeneration of the liver, a greater number of HCC nodules and larger (Fig. 3A). According to in vitro results in HepG2 and Snu449 cells, in the invasive edge of Vidatox treated HCCs there are more cells that penetrate the non-tumor liver tissue surrounding the HCC nodule (Fig. ...
Context 4
... was purchased online. HepG2 cells were seeded into 6-well dishes and allowed to attach for 24 hours before treatments. Vidatox protein concentration, quantified by Lowry method, was 0.04 mg/ml. Two drops of Vidatox (75 μ l), corresponding to 3ug of protein, were added in each well using a 100 μ l pipet filter tip, whereas negative controls were obtained by adding two drops of 33% ethanol. The amount of Vidatox was established by a concentration growth inhibition study in HepG2 and Snu449 cells (Supplemental Fig. 2). Apoptosis was cytometer. The same protocol was used for HEP10 normal hepatocytes which were not sychronizated since they are enable to ...

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... With natural selection, different types and subtypes of receptors (ion channels) co-evolved in various animal groups; coincidently, specific ligands related to peptides with toxin activity evolved in scorpions [15][16][17]. Toxins produced by scorpions have attracted the scientific community's attention for their therapeutic properties; an example is the Cuban blue scorpion Rhopalurus junceus, which is used in oncologic therapy and other species for having antimicrobial activity against bacteria and fungi [18,19]. AMPs are amphipathic with a positive charge. ...
Article
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Microbial infections represent a problem of great importance at the public health level, with a high rate of morbidity-mortality worldwide. However, treating the different diseases generated by microorganisms requires a gradual increase in acquired resistance when applying or using them against various antibiotic therapies. Resistance is caused by various molecular mechanisms of microorganisms, thus reducing their effectiveness. Consequently, there is a need to search for new opportunities through natural sources with antimicrobial activity. One alternative is using peptides present in different scorpion venoms, specifically from the Buthidae family. Different peptides with biological activity in microorganisms have been characterized as preventing their growth or inhibiting their replication. Therefore, they represent an alternative to be used in the design and development of new-generation antimicrobial drugs in different types of microorganisms, such as bacteria, fungi, viruses, and parasites. Essential aspects for its disclosure, as shown in this review, are the studies carried out on different types of peptides in scorpion venoms with activity against pathogenic microorganisms, highlighting their high therapeutic potential.
... With natural selection, different types and subtypes of receptors (ion channels) co-evolved in various animal groups; coincidently, specific ligands related to peptides with toxin activity evolved in scorpions [15][16][17]. Toxins produced by scorpions have attracted the scientific community's attention for their therapeutic properties; an example is the Cuban blue scorpion Rhopalurus junceus, which is used in oncologic therapy and other species for having antimicrobial activity against bacteria and fungi [18,19]. AMPs are amphipathic with a positive charge. ...
Article
Full-text available
Microbial infections represent a problem of great importance at the public health level, with a high rate of morbidity-mortality worldwide. However, treating the different diseases generated by microorganisms requires a gradual increase in acquired resistance when applying or using them against various antibiotic therapies. Resistance is caused by various molecular mechanisms of microorganisms, thus reducing their effectiveness. Consequently, there is a need to search for new opportunities through natural sources with antimicrobial activity. One alternative is using peptides present in different scorpion venoms, specifically from the Buthidae family. Different peptides with biological activity in microorganisms have been characterized as preventing their growth or inhibiting their replication. Therefore, they represent an alternative to be used in the design and development of new-generation antimicrobial drugs in different types of microorganisms, such as bacteria, fungi, viruses, and parasites. Essential aspects for its disclosure, as shown in this review, are the studies carried out on different types of peptides in scorpion venoms with activity against pathogenic microorganisms, highlighting their high therapeutic potential.
... Currently published articles investigate the composition and in vitro anticancer activity of the venom; there are no controlled clinical trials evaluating toxicity or effectiveness. [5][6][7][8] Giovannini et al. 6 reported that Vidatox 30 CH (venom extracted from the R. junceus scorpion) increased hepatocellular carcinoma cell proliferation and invasion in rats. Manufacturer states that it acts via ion channels that are important in cellular signaling. ...
... Currently published articles investigate the composition and in vitro anticancer activity of the venom; there are no controlled clinical trials evaluating toxicity or effectiveness. [5][6][7][8] Giovannini et al. 6 reported that Vidatox 30 CH (venom extracted from the R. junceus scorpion) increased hepatocellular carcinoma cell proliferation and invasion in rats. Manufacturer states that it acts via ion channels that are important in cellular signaling. ...
Article
Historically snake, scorpion, and hymenoptera venom have been used to treat various diseases. It is well known that alternative and/or complementary treatment options are widely used, especially among cancer patients. The case we describe here has lung carcinoma and received blue scorpion venom as an alternative therapy. A 86 years old male patient was admitted complaining of dyspnea. Thorax computed tomography (CT) showed a mass lesion and intraparenchymal nodules on the left upper lobe. Percutaneous transthoracic biopsy was performed, and the diagnosis was reported to be an epidermoid carcinoma. After the shared decision, A shared decision with the family and oncology specialists, the patient decided to try Cuban blue scorpion venom oral drops. Initially, it was well tolerated. However on the sixth day of treatment, sudden death occurred. Scorpion venom has been considered as a natural source for cancer therapy. Rhopalurus junceus is an endemic scorpion species from Cuba. Although it belongs to the most dangerous species related to human scorpionism, and no fatal stings have been reported. Currently published articles investigate the composition and in vitro anticancer activity of the venom; there are no controlled clinical trials evaluating toxicity or effectiveness. Uncontrolled use of alternative treatment options may lead to unexpected interactions with concomitant medications.
... As a final delivery vehicle for all HUBC, sterile lactose globules (#2 pills) were fully impregnated to saturation with the respective treatment. Pills were dried at room temperature (24 h, 25°C) to evaporate ethanol and prevent their potential side effects (Giovannini et al., 2017), protecting them from ambient powder and contaminants; finally, they were kept in darkness in tightly closed amber glass bottles. ...
Article
Ultra‐diluted bioactive compounds have emerged as an alternative to enhance marine organism performance and to improve broodstock gonad maturation. This study evaluated for the first time the effect of three homeopathically ultra‐diluted bioactive compounds (HUBC’s) authorized by the health authority as medicines for humans, on the general reproductive physiology of Argopecten ventricosus, a commercially important scallop species. The experiment included three HUBC’s treatments at centesimal dilution assessed in triplicate under laboratory conditions, T1: PaV‐30C + PhA‐30C, T2: PaV‐30C + SiT‐30C, and T3: ViT‐30C, and a non‐treated field reference group (FRG) maintained in aquaculture facilities as reference. The bioenergetics of scallop reproduction and oocyte quality increased with the three HUBC treatments, but particularly in those treated with T2. The organisms treated with T3 showed not only the highest proliferation of vitellogenic and post‐vitellogenic oocytes but also the greatest oxidative damage in tissues and oocytes. In contrast, the scallops from T1 and T2 showed less oxidative damage. The results suggest that ultra‐diluted formula T2 is a potential alternative to optimize A. ventricosus gonad ripening, food‐nutrient management and oocyte quality because although T3 allowed accelerating the gametogenesis process, it increased oxidative damage. This study could help to improve gonad broodstock condition and larval yield of this species in hatcheries.
... We included seven studies in the quantitative analysis: Diaz-Garcia et al. 2013 [2], Diaz-Garcia et al. 2015 [10], Giovannini et al. 2017 [11], Diaz-Garcia et al. 2017 [12], Diaz-Garcia et al. 2019 [13], Yglesias-Rivera et al. 2019 [15], and Lozano-Trujillo et al. 2020 [16]. Four of these were the studies from which the data for the meta-analysis were extracted ( Table 2). ...
... The studies presented in Table 3 were excluded from the meta-analysis. Giovannini et al. 2017 reported the effects of Vidatox 30, which is the hematopoietic derivative of venom [11]. Yglesias-Rivera et al. 2019 reported data regarding a synergistic effect between antineoplastic drugs and scorpion venom. ...
... The studies presented in Table 3 were excluded from the meta-analysis. Giovannini et al. 2017 reported the effects of Vidatox 30, which is the hematopoietic derivative of venom [11]. Yglesias-Rivera et al. 2019 reported data regarding a synergistic effect between antineoplastic drugs and scorpion venom. ...
Article
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The Rhopalurus junceus is a scorpion belonging to the Buthidae family that finds its habitat in Cuba. This scorpion is known by the common name of “Blue Scorpion”. The venom is used on the island of Cuba as an alternative cure for cancer and, more recently, in the research of active components for biomedicine. Recently, the venom has been tested in several studies to investigate its effects on cancer cell lines, and the initial results of in vitro studies demonstrated how this poison can be effective on certain carcinoma cell lines (Hela, SiHa, Hep-2, NCI-H292, A549, MDA-MB-231, MDA-MB-468, and HT-29). The aim of this review is, therefore, to describe the effects of the venom on carcinoma lines and to investigate all anti-cancer properties studied in the literature. The research was conducted using four databases, Pub Med, Scopus, EBSCO, and Web of Science, through the use of keywords, by two independent reviewers following the PRISMA protocol, identifying 57 records. The results led to a total of 13 articles that met the eligibility criteria. The data extracted for the purpose of meta-analysis included the IC50 of the venom on carcinoma cell lines. The results of the meta-analysis provided a pooled mean of the IC50 of 0.645 mg/mL (95% CI: 0.557, 0.733), with a standard error (SE) = 0.045, p < 0.001. The analysis of the subgroups, differentiated by the type of cell line used, provided insight regarding how the scorpion venom was effective on the cell lines of lung origin (NCI-H292, A549, and MRC-5) with a pooled mean of IC50 0.460 mg/mL (95% CI: 0.290, 0.631) SE (0.087) p < 0.001. The results described in the literature for in vitro studies are encouraging, and further investigations should be carried out and deepened.
... As mentioned before, T4 behaved differently compared to the rest of the treatments and mainly activated the melanogenesis and haematopoietic processes and a gene associated to calcium transport (TRPM2), which have been linked to immune response when organisms are challenged against bacteria [70,71]; however, the immunomodulatory effect of Vidatox1 was not clear. Vidatox1 has demonstrated to increase SOD activity and survival of L. vannamei when it has been challenged against pathogenic bacteria [91], but it has also been related to proliferation of hepatocellular carcinoma in cultured mouse cells [92]. As in the other treatments, oxidative phosphorylation in mitochondria was modulated by the effect of T4. ...
Article
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Marine bivalve hatchery productivity is continuously challenged by apparition and propagation of new diseases, mainly those related to vibriosis. Disinfectants and antibiotics are frequently overused to prevent pathogen presence, generating a potential negative impact on the environment. Recently, the use of highly diluted compounds with immunostimulant properties in marine organisms has been trailed successfully to activate the self-protection mechanisms of marine bivalves. Despite their potential as immunostimulants, little is known about their way of action. To understand their effect, a comparative transcriptomic analysis was performed with Argopecten ventricosus juveniles. The experimental design consisted of four treatments formulated from pathogenic Vibrio lysates at two dilutions: [(T1) Vibrio parahaemolyticus and Vibrio alginolyticus 1D; (T2) V. parahaemolyticus and V. alginolyticus 7C]; minerals [(T3) PhA+SiT 7C], scorpion venom [(T4) ViT 31C]; and one control (C1) hydro-alcoholic solution (ethanol 1%). The RNA sequencing (RNAseq) analysis showed a higher modulation of differentially expressed genes (DEG) in mantle tissue compared to gill tissue. The scallops that showed a higher number of DEG related to immune response in mantle tissue corresponded to T1 (V. parahaemolyticus and V. alginolyticus lysate) and T3 (Silicea terra® - Phosphoric acid®). The transcriptome analysis allowed understanding some interactions between A. ventricosus juveniles and highly-diluted treatments.
... As mentioned before, T4 behaved differently compared to the rest of the treatments and mainly activated the melanogenesis and haematopoietic processes and a gene associated to calcium transport (TRPM2), which have been linked to immune response when organisms are challenged against bacteria [70,71]; however, the immunomodulatory effect of Vidatox1 was not clear. Vidatox1 has demonstrated to increase SOD activity and survival of L. vannamei when it has been challenged against pathogenic bacteria [91], but it has also been related to proliferation of hepatocellular carcinoma in cultured mouse cells [92]. As in the other treatments, oxidative phosphorylation in mitochondria was modulated by the effect of T4. ...
... The observed arrests in the cell cycle could be an indication of tumor suppressor p21 upregulation and could, hence, suggest selectivity toward cancer cells. Anticancer properties have been recently associated to the crude venom of Rhopalurus junceus and a mix of five peptides from the same venom [223,224]. Despite generating promising results, further investigations on the aforementioned scorpion crude venoms are needed to characterize the effective anticancer constituents among other venom components. ...
Article
Full-text available
Scorpion venom may cause severe medical complications and untimely death if injected into the human body. Neurotoxins are the main components of scorpion venom that are known to be responsible for the pathological manifestations of envenoming. Besides neurotoxins, a wide range of other bioactive molecules can be found in scorpion venoms. Advances in separation, characterization, and biotechnological approaches have enabled not only the development of more effective treatments against scorpion envenomings, but have also led to the discovery of several scorpion venom peptides with interesting therapeutic properties. Thus, scorpion venom may not only be a medical threat to human health, but could prove to be a valuable source of bioactive molecules that may serve as leads for the development of new therapies against current and emerging diseases. This review presents both the detrimental and beneficial properties of scorpion venom toxins and discusses the newest advances within the development of novel therapies against scorpion envenoming and the therapeutic perspectives for scorpion toxins in drug discovery.
... There was a synergistic effect of this poison combined with low concentrations of cytostatic fluorouracil, doxorubicin, and cisplatin on HeLa cervical cancer cells (Díaz et al., 2013;Díaz et al., 2017;Yglesias et al., 2019). However, Giovannini et al., (2017) when analyzing the effect of a preparation based on this poison in hepatocellular carcinoma (HCC), they found that it induced cell proliferation and improved the expression of the vascular endothelial growth factor receptor (VEGFR) associated with angiogenesis and metastasis capacity. Suggesting good research in molecular biology for these poisons and use them with caution (Giovannini et al., 2017). ...
... However, Giovannini et al., (2017) when analyzing the effect of a preparation based on this poison in hepatocellular carcinoma (HCC), they found that it induced cell proliferation and improved the expression of the vascular endothelial growth factor receptor (VEGFR) associated with angiogenesis and metastasis capacity. Suggesting good research in molecular biology for these poisons and use them with caution (Giovannini et al., 2017). ...
Article
Full-text available
Cancer is a public health problem due to its high worldwide morbimortality. Current treatment protocols do not guarantee complete remission, which has prompted to search for new and more effective antitumoral compounds. Several substances exhibiting cytostatic and cytotoxic effects over cancer cells might contribute to the treatment of this pathology. Some studies indicate the presence of such substances in scorpion venom. In this review, we report characteristics of the principal scorpion venom components found in recent literature and their potential activity against tumor cells. There are different toxin groups present in the venom, and it seems that their mode of actions involves ionic channel blocking, disruption of the cell membrane integrity and damage to internal cell organelles. These properties make good prospects for studies on drugs and adjuvants in cancer treatment.
... It is a registered trademark of a commercial homeopathic drug from the scorpion Rhopalurus juneceus venoms and sold to treat cancer in humans (http://vidatoxromania.ro/en/what-is-vidatox/). Nonetheless, Giovannini et al. (2017) observed that it could induce hepatocellular carcinoma proliferation in culture mouse cells. Thus, it has to be handled carefully because these authors used the commercial solution Vidatox®, which is a hydroalcoholic solution (30°GL), and carcinoma proliferation could be an effect of the alcohol itself. ...
Article
Full-text available
The future of the bivalve mollusk production sector worldwide is still challenged by emergence and propagation of new diseases, mainly vibriosis, and the conventional methods that have been used to eradicate pathogens from hatcheries, such as antibiotics and chemotherapies have shown collateral effects. In order to reduce the use of conventional methods, homeopathy for aquaculture emerges as a novel solution to strengthen marine organism's defense against diseases. This study evaluated the effect of five homeopathic treatments on the immunomodulatory response and general condition index of Argopecten ventricosus juveniles, used as model organisms due to their susceptibility to vibriosis compared to other commercial bivalves. The experimental design included three replicates of five homeopathic treatments at decimal (D) or centesimal (C) dynamization (T1: ViA 1D + ViP 1D, T2: ViA 7C + ViP 7C, T3: AcF 1D + MsS 1D, T4: PhA 7C + SiT 7C and T5: ViT 31C) and three control groups (C1: Dynamized Ethanol (1C), C2: Diluted Ethanol (1:99) and C3: No medication). The maximum immunomodulatory response was attributed to treatments T1 and T2 with the highest increase in hemocyte count, catalase activity in mantle and superoxide dismutase activity in gills, followed by treatments T3 and T5. Treatment T4 did not show a definite effect on an immune response but increased energetic reserves in the mantle, muscle and the digestive gland, important storage tissues in mollusk bivalves. This study has demonstrated that some homeopathic treatments can activate an immunomodulatory response and improve the general condition index in A. ventricosus.