Gentian Violet: a 19th century drug re‐emerges in the 21st century

Gentian violet (GV) has a long and varied history as a medicinal agent. Historically used as an antibacterial and antifungal, recent reports have shown its utility as an antitypranosomal, antiviral and anti‐angiogenic agent. The objective of this article is to summarize evidence regarding the efficacy and safety of GV use in dermatology. Recent discoveries have found novel targets of GV, namely NADPH oxidase in mammalian cells and thioredoxin reductase 2 in bacterial, fungal and parasitic cells. These discoveries have expanded the use of GV in the 21st century. Given that GV is well tolerated, effective and inexpensive, its use in dermatology is predicted to increase.

[1]  R. W. John Necrosis of Oral Mucosa after Local Application of Crystal Violet , 1968, British medical journal.

[2]  Cynthia Cohen,et al.  Reactive oxygen generated by Nox1 triggers the angiogenic switch , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[3]  F. J. Gustina,et al.  The treatment of pinworm infection (enterobiasis) with gentian violet suspension. , 1955, The Journal of pediatrics.

[4]  E. Isogai,et al.  Frequent detection of ‘azole’ resistant Candida species among late presenting AIDS patients in northwest Ethiopia , 2013, BMC Infectious Diseases.

[5]  S. Wendel Transfusion transmitted Chagas disease: is it really under control? , 2010, Acta tropica.

[6]  J. Arbiser,et al.  Transgrediens pachyonychia congenita (PC): case series of a nonclassical PC presentation , 2012, The British journal of dermatology.

[7]  K. Nibu,et al.  Effects of gentian violet on refractory discharging ears infected with methicillin-resistant Staphylococcus aureus. , 2006, The Journal of Otolaryngology.

[8]  H. Takagi,et al.  High-pressure irrigation and gentian-violet application for mediastinitis following replacement of ascending aorta and aortic valve , 2006, Heart and Vessels.

[9]  M. Lapidoth,et al.  Efficacy of topical application of eosin for ulcerated hemangiomas. , 2009, Journal of the American Academy of Dermatology.

[10]  J. Churchman THE SELECTIVE BACTERICIDAL ACTION OF GENTIAN VIOLET , 1912, The Journal of experimental medicine.

[11]  R. Docampo,et al.  Crystal violet as an uncoupler of oxidative phosphorylation in rat liver mitochondria. , 1988, The Journal of biological chemistry.

[12]  D. Hinton RESULTS OF THE INTRAVENOUS USE OF GENTIAN VIOLET IN CASES OF EXTREME SEPTICAEMIA. , 1925, Annals of surgery.

[13]  W. E. Askue A comparison of egressin and gentian violet in the treatment of enterobiasis (pinworm infestation). , 1953, The Journal of pediatrics.

[14]  A. Molassiotis,et al.  The effects of hydrocolloid dressing and gentian violet on radiation-induced moist desquamation wound healing. , 2000, Cancer nursing.

[15]  E. Lages-Silva,et al.  Prevention of transfusion‐associated Chagas' disease by sterilization of Trypanosoma cruzi‐infected blood with gentian violet, ascorbic acid, and light , 1995, Transfusion.

[16]  Y. Tabe,et al.  Comparison of Antifungal Activities of Gentian Violet and Povidone-Iodine Against Clinical Isolates of Candida Species and Other Yeasts: A Framework to Establish Topical Disinfectant Activities , 2011, Mycopathologia.

[17]  J. Arbiser,et al.  Effectiveness of gentian violet and similar products commonly used to treat pyodermas. , 2011, Dermatologic clinics.

[18]  Y. Ouchi,et al.  [Randomized prospective trial of gentian violet with dibutyryl cAMP and povidone-iodine with sugar as treatment for pressure sores infected with methicillin-resistant Staphylococcus aureus in elderly patients]. , 1997, Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics.

[19]  W. de Souza,et al.  Prevention of Chagas' disease resulting from blood transfusion by treatment of blood: toxicity and mode of action of gentian violet. , 1988, Biomedical and environmental sciences : BES.

[20]  M. Azuma,et al.  Immunoregulatory molecule B7-H1 (CD274) contributes to skin carcinogenesis. , 2011, Cancer research.

[21]  V. Suman,et al.  Phase 2 trial of carboplatin, weekly paclitaxel, and biweekly bevacizumab in patients with unresectable stage IV melanoma , 2009, Cancer.

[22]  P. Bergeson,et al.  Gentian Violet Toxicity , 1992, Clinical pediatrics.

[23]  J. Arbiser,et al.  Targeting NADPH oxidases for the treatment of cancer and inflammation , 2012, Cellular and Molecular Life Sciences.

[24]  A. E. Stearn,et al.  THE MECHANICAL BEHAVIOR OF DYES, ESPECIALLY GENTIAN VIOLET, IN BACTERIOLOGICAL MEDIA , 1923, Journal of bacteriology.

[25]  R. Docampo,et al.  Inhibition of Protein Synthesis and Amino Acid Transport by Crystal Violet in Trypanosoma cruzi , 1995, The Journal of eukaryotic microbiology.

[26]  Carlene A. Muto,et al.  A randomized crossover study of silver-coated urinary catheters in hospitalized patients. , 2000, Archives of internal medicine.

[27]  H. Augustin,et al.  Angiopoietins: a link between angiogenesis and inflammation. , 2006, Trends in immunology.

[28]  Betty Y. Y. Tam,et al.  VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. , 2006, American journal of physiology. Heart and circulatory physiology.

[29]  R. Swindell,et al.  RCT on gentian violet versus a hydrogel dressing for radiotherapy-induced moist skin desquamation. , 2008, Journal of Wound Care.

[30]  T. Hsu,et al.  Cytogenetic toxicity of gentian violet and crystal violet on mammalian cells in vitro. , 1978, Mutation research.

[31]  J. Maree,et al.  Treatment of oral thrush in HIV/AIDS patients with lemon juice and lemon grass (Cymbopogon citratus) and gentian violet. , 2009, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[32]  D. Gaylor,et al.  Chronic Toxicity and Carcinogenicity Studies of Gentian Violet in Mice , 1985 .

[33]  A. Walsh,et al.  Haemorrhagic cystitis due to gentian violet. , 1986, British medical journal.

[34]  M. Porotto,et al.  Antiviral activity of gliotoxin, gentian violet and brilliant green against Nipah and Hendra virus in vitro , 2009, Virology Journal.

[35]  S. Faithfull,et al.  Radiotherapy skin care: A survey of practice in the UK , 2012 .

[36]  D. McDonald,et al.  Complementary actions of inhibitors of angiopoietin-2 and VEGF on tumor angiogenesis and growth. , 2010, Cancer research.

[37]  D. Brat,et al.  Anti-Invasive Adjuvant Therapy with Imipramine Blue Enhances Chemotherapeutic Efficacy Against Glioma , 2012, Science Translational Medicine.

[38]  A. Rademaker,et al.  Treatment of Staphylococcus aureus Colonization in Atopic Dermatitis Decreases Disease Severity , 2009, Pediatrics.

[39]  R. Mason,et al.  Light-enhanced free radical formation and trypanocidal action of gentian violet (crystal violet). , 1983, Science.

[40]  M. Heller,et al.  Caring for new mothers: diagnosis, management and treatment of nipple dermatitis in breastfeeding mothers , 2012, International journal of dermatology.

[41]  E. S. Sanderson,et al.  The Effect of Gentian Violet on the Organism of Blastomycotic Infection. , 1927 .

[42]  M. Ghannoum,et al.  In vitro activity of inexpensive topical alternatives against Candida spp. isolated from the oral cavity of HIV-infected patients. , 2008, International journal of antimicrobial agents.

[43]  G. Yancopoulos,et al.  Pharmacologic blockade of angiopoietin-2 is efficacious against model hemangiomas in mice. , 2006, The Journal of investigative dermatology.

[44]  T. Svidzinski,et al.  The effect of chlorhexidine and gentian violet on the adherence of Candida spp. to urinary catheters , 2007, Mycopathologia.

[45]  Yihai Cao Angiogenesis: What can it offer for future medicine? , 2010, Experimental cell research.

[46]  J. Arbiser,et al.  A nonsteroidal alternative to impetiginized eczema in the emergency room. , 2010, Journal of the American Academy of Dermatology.

[47]  M. Mihm,et al.  Topical rapamycin suppresses the angiogenesis pathways induced by pulsed dye laser: Molecular mechanisms of inhibition of regeneration and revascularization of photocoagulated cutaneous blood vessels , 2012, Lasers in surgery and medicine.

[48]  R. Ganju,et al.  Melanoma Cell Expression of CD200 Inhibits Tumor Formation and Lung Metastasis via Inhibition of Myeloid Cell Functions , 2012, PloS one.

[49]  守 佐治,et al.  Methicillin-resistant Staphylococcus aureus (MRSA) 感染褥瘡に対するゲンチアナバイオレットの除菌効果の検討 , 1993 .

[50]  Ralph L Kodell,et al.  Carcinogenicity of malachite green chloride and leucomalachite green in B6C3F1 mice and F344 rats. , 2006, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[51]  Bernard Choi,et al.  Long‐term blood vessel removal with combined laser and topical rapamycin antiangiogenic therapy: Implications for effective port wine stain treatment , 2010, Lasers in surgery and medicine.

[52]  M. McCarter,et al.  Melanoma skews dendritic cells to facilitate a T helper 2 profile. , 2005, Surgery.

[53]  N. Wieringa,et al.  ACTIVITY OF GENTIAN VIOLET AND BRILLIANT GREEN AGAINST SOME MICROORGANISMS ASSOCIATED WITH SKIN INFECTIONS , 1992, International journal of dermatology.

[54]  Mamoru Saji Methicillin-Resistant Staphylococcus aureus感染病巣に対する有機色素剤gentiana violetの局所治療剤としての検討 , 1992 .

[55]  K. Sundaram,et al.  Studies on antibacterial properties of gentian violet impregnated silastic. , 1993, The Indian journal of medical research.

[56]  B. Wilson-Clay More on Thrush and the Use of Gentian Violet , 1991, Journal of human lactation : official journal of International Lactation Consultant Association.

[57]  D. L. Farley THE USE OF GENTIAN-VIOLET AS A RESTRAINER IN THE ISOLATION OF THE PATHOGENIC MOLDS , 1920 .

[58]  B. A. Fry Basic triphenylmethane dyes and the inhibition of glutamine synthesis by Staphylococcus aureus. , 1957, Journal of general microbiology.

[59]  Effect of dyes on bacterial growth. , 1973, Applied microbiology.

[60]  B. Lefkove,et al.  Disruption of the mitochondrial thioredoxin system as a cell death mechanism of cationic triphenylmethanes. , 2011, Free radical biology & medicine.

[61]  M. Ishii,et al.  Intercellular pathway through hyaluronic acid in UVB‐induced inflammation , 2012, Experimental dermatology.

[62]  J. Costerton,et al.  Antibiotic resistance of bacteria in biofilms , 2001, The Lancet.

[63]  P. Beaver,et al.  Treatment of enterobiasis (pinworm infestation) with diphenan, egression and gentian violet. , 1953, Pediatrics.

[64]  Ravi Bellamkonda,et al.  Identifying new small molecule anti-invasive compounds for glioma treatment , 2013, Cell cycle.

[65]  Dai Fukumura,et al.  Vascular normalization as an emerging strategy to enhance cancer immunotherapy. , 2013, Cancer research.

[66]  Y. Inoue,et al.  Drainage surgery followed by postoperative irrigation with gentian violet for prosthetic graft infection caused by methicillin-resistant Staphylococcus aureus. , 2011, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[67]  Yihai Cao,et al.  Optimizing the Delivery of Cancer Drugs That Block Angiogenesis , 2010, Science Translational Medicine.

[68]  守 佐治,et al.  Methicillin-resistant Staphylococcus aureus感染局所治療剤としての各種色素剤の抗菌効果に関する検討 , 1993 .

[69]  R. Mason,et al.  Microsomal reduction of gentian violet. Evidence for cytochrome P-450-catalyzed free radical formation. , 1982, Molecular pharmacology.

[70]  J. Arbiser Gentian violet is safe. , 2009, Journal of the American Academy of Dermatology.

[71]  H. Faber,et al.  THE TREATMENT OF THRUSH WITH GENTIAN VIOLET , 1925 .

[72]  J. Arbiser,et al.  Targeted therapy of oral hairy leukoplakia with gentian violet. , 2008, Journal of the American Academy of Dermatology.

[73]  J. Matsuo,et al.  Frequency of Chlamydia trachomatis in Ureaplasma-positive healthy women attending their first prenatal visit in a community hospital in Sapporo, Japan , 2012, BMC Infectious Diseases.

[74]  H. J. Conn AN INVESTIGATION OF AMERICAN GENTIAN VIOLETS REPORT OF COMMITTEE ON BACTERIOLOGICAL TECHNIC , 1922 .

[75]  E. Slotkowski,et al.  Mucosal irritation following use of gentian violet. , 1966, American journal of diseases of children.

[76]  H. Pass,et al.  Peroxiredoxin 3 Is a Redox-Dependent Target of Thiostrepton in Malignant Mesothelioma Cells , 2012, PloS one.

[77]  D. Koh,et al.  Hemorrhagic cystitis due to intravesical instillation of gentian violet completely recovered with conservative therapy. , 2003, Yonsei medical journal.

[78]  Tobias Pincock Fitzpatrick's Dermatology in General Medicine , 2003 .

[79]  Clifford Parsons,et al.  Possible hazard in use of gentian violet. , 1971, British medical journal.

[80]  D. McDermott,et al.  Multicenter, Phase II Study of Axitinib, a Selective Second-Generation Inhibitor of Vascular Endothelial Growth Factor Receptors 1, 2, and 3, in Patients with Metastatic Melanoma , 2011, Clinical Cancer Research.

[81]  D. E. Levin,et al.  Light-enhanced genetic toxicity of crystal violet. , 1982, Mutation research.

[82]  M. Ghannoum,et al.  Gentian Violet Exhibits Activity against Biofilms Formed by Oral Candida Isolates Obtained from HIV-Infected Patients , 2011, Antimicrobial Agents and Chemotherapy.

[83]  G. A. Grant Peterkin,et al.  Impetigo in the Services , 1943 .

[84]  M. A. Ingraham The Bacteriostatic Action of Gentian Violet and Dependence on the Oxidation-Reduction Potential , 1933, Journal of bacteriology.

[85]  E. Cullen,et al.  Obstructive Laryngotracheitis Secondary to Gentian Violet Exposure , 2001, Clinical pediatrics.

[86]  G. Gleich,et al.  Hypereosinophilic syndrome: case presentation and update. , 2004, The Journal of allergy and clinical immunology.

[87]  M. Okano,et al.  Topical gentian violet for cutaneous infection and nasal carriage with MRSA , 2000, International journal of dermatology.

[88]  D. Munn,et al.  Indoleamine 2,3-dioxygenase and tumor-induced tolerance. , 2007, The Journal of clinical investigation.

[89]  J. Arbiser,et al.  Application of angiogenesis to clinical dermatology. , 2008, Advances in dermatology.

[90]  M. Butler,et al.  Further study of the genetic toxicity of gentian violet. , 1979, Mutation research.

[91]  A. Utter Gentian Violet Treatment for Thrush: Can its Use Cause Breastfeeding Problems? , 1990, Journal of human lactation : official journal of International Lactation Consultant Association.

[92]  Yihai Cao Antiangiogenic cancer therapy: why do mouse and human patients respond in a different way to the same drug? , 2011, The International journal of developmental biology.

[93]  Ying Jiang,et al.  Novel Antiseptic Urinary Catheters for Prevention of Urinary Tract Infections: Correlation of In Vivo and In Vitro Test Results , 2009, Antimicrobial Agents and Chemotherapy.

[94]  K. Nordström,et al.  Outer Penetration Barrier of Escherichia coli K-12: Kinetics of the Uptake of Gentian Violet by Wild Type and Envelope Mutants , 1973, Journal of bacteriology.

[95]  R. Aldrich The Role of Infection in Burns , 1933 .

[96]  J. Verbov Oral irritation with gentian violet. , 1976, British medical journal.

[97]  P. Contacos,et al.  Treatment of Strongyloides stercoralis infection with intravenous gentian violet. , 1957, The American journal of tropical medicine and hygiene.

[98]  S. Moreno,et al.  Metabolism and mode of action of gentian violet. , 1988, Memorias do Instituto Oswaldo Cruz.

[99]  I. Raad,et al.  A rapid method of impregnating endotracheal tubes and urinary catheters with gendine: a novel antiseptic agent. , 2005, The Journal of antimicrobial chemotherapy.

[100]  B. Lefkove,et al.  Triphenylmethane Derivatives Have High In Vitro and In Vivo Activity against the Main Causative Agents of Cutaneous Leishmaniasis , 2013, PloS one.

[101]  M. Biggs,et al.  Suppression of immune surveillance in melanoma. , 2001, Medical hypotheses.

[102]  R. Chole,et al.  Gentian Violet and Ferric Ammonium Citrate Disrupt Pseudomonas Aeruginosa Biofilms , 2008, The Laryngoscope.

[103]  J. Ring,et al.  Effect of Gentian Violet, Corticosteroid and Tar Preparations in Staphylococcus-aureus-Colonized Atopic Eczema , 1999, Dermatology.

[104]  E. Wald,et al.  Group B beta-hemolytic streptococcal colonization. Acquisition, persistence, and effect of umbilical cord treatment with triple dye. , 1977, American journal of diseases of children.

[105]  J. Stilling THE ANILINE DYES AS ANTISEPTICS. , 1891 .