Rose bengal (4,5,6,7-tetrachloro-2',4',5',7'-tetraiodofluorescein) is a

stain A stain is a discoloration that can be clearly distinguished from the surface, material, or medium it is found upon. They are caused by the chemical or physical interaction of two dissimilar materials. Accidental staining may make materials app ...

. Rose bengal belongs to the class of

organic compounds In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The s ...

called

xanthene Xanthene (9''H''-xanthene, 10''H''-9-oxaanthracene) is the organic compound with the formula CH2 6H4sub>2O. It is a yellow solid that is soluble in common organic solvents. Xanthene itself is an obscure compound, but many of its derivatives are us ...

s. Its sodium salt is commonly used in

eye drop Eye drops or eyedrops are liquid drops applied directly to the surface of the eye usually in small amounts such as a single drop or a few drops. Eye drops usually contain saline to match the salinity of the eye. Drops containing only saline ...

s to stain damaged

conjunctiva The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epithelium ...

l and

cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...

l cells and thereby identify damage to the eye. The stain is also used in the preparation of

Foraminifera Foraminifera (; Latin for "hole bearers"; informally called "forams") are single-celled organisms, members of a phylum or class of amoeboid protists characterized by streaming granular Ectoplasm (cell biology), ectoplasm for catching food and ot ...

for microscopic analysis, allowing the distinction between forms that were alive or dead at the time of collection. A form of rose bengal is also being studied as a treatment for certain cancers and skin conditions. The cancer formulation of the drug, known as PV-10, is currently undergoing clinical trials for

melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

. an
neuroendocrine tumors
The company also has formulated a drug based on rose bengal for the treatment of

eczema Dermatitis is inflammation of the Human skin, skin, typically characterized by itchiness, erythema, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become lichenification, thick ...

and

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...

; this drug, PV-10, is currently in clinical trials as well.

History and etymology

Rose bengal was originally prepared in 1882 by Swiss chemist Robert Ghnem, as an analogue of

fluorescein Fluorescein is an organic compound and dye based on the xanthene tricyclic structural motif, formally belonging to triarylmethine dyes family. It is available as a dark orange/red powder slightly soluble in water and alcohol. It is widely used ...

. Rudolf Nietzki at the

University of Basel The University of Basel (Latin: ''Universitas Basiliensis'', German: ''Universität Basel'') is a university in Basel, Switzerland. Founded on 4 April 1460, it is Switzerland's oldest university and among the world's oldest surviving universit ...

identified the principal constituents of rose bengal as

iodine Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , and boils to a vi ...

derivatives of di- and tetra-chlorofluorescein. The compound was originally used as a wool dye. Its name derives from

rose A rose is either a woody perennial flowering plant of the genus ''Rosa'' (), in the family Rosaceae (), or the flower it bears. There are over three hundred species and tens of thousands of cultivars. They form a group of plants that can be ...

(flower) and

Bengal Bengal ( ; bn, বাংলা/বঙ্গ, translit=Bānglā/Bôngô, ) is a geopolitical, cultural and historical region in South Asia, specifically in the eastern part of the Indian subcontinent at the apex of the Bay of Bengal, predom ...

(region); it is printed as rose bengal or Rose Bengal in the scientific literature.

Chemical applications

Despite its complicated

photochemistry Photochemistry is the branch of chemistry concerned with the chemical effects of light. Generally, this term is used to describe a chemical reaction caused by absorption of ultraviolet (wavelength from 100 to 400 nm), visible light (400–7 ...

involving several species, rose bengal is also used in synthetic chemistry to generate

singlet oxygen Singlet oxygen, systematically named dioxygen(singlet) and dioxidene, is a gaseous inorganic chemical with the formula O=O (also written as or ), which is in a quantum state where all electrons are spin paired. It is kinetically unstable at ambie ...

from

triplet oxygen Triplet oxygen, 3O2, refers to the ''S'' = 1 electronic ground state of molecular oxygen (dioxygen). It is the most stable and common allotrope of oxygen. Molecules of triplet oxygen contain two unpaired electrons, making triplet oxygen an unus ...

. The singlet oxygen can then undergo a variety of useful reactions, particularly + 2

cycloaddition In organic chemistry, a cycloaddition is a chemical reaction in which "two or more Unsaturated hydrocarbon, unsaturated molecules (or parts of the same molecule) combine with the formation of a cyclic adduct in which there is a net reduction of th ...

s with

alkene In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...

s and similar systems.

Derivatives and salts

Rose bengal can be used to form many derivatives that have important medical functions. One such derivative was created so to be sonosensitive but photoinsensitive, so that with a high intensity focused ultrasound, it could be used in the treatment of cancer. The derivative was formed by amidation of rose bengal, which turned off the fluorescent and photosensitive properties of rose bengal, leading to a usable compound, named in the study as RB2. Rose_bengal_sodium_salt_structure

Salts of rose bengal include C₂₀H₄Cl₄I₄O₅·2Na (CAS 632-69-9). This sodium salt is a dye, which has its own unique properties and uses.

Biological applications

PV-10 (an injectable form of rose bengal) was found to cause an observable response in 60% of tumors treated, according to researchers in a phase II

study. Locoregional disease control was observed in 75% of patients. Also confirmed was a "bystander effect", previously observed in the phase I trial, whereby untreated lesions responded to treatment as well, potentially due to immune system response. These data were based on the interim results (in 2009) of the first 40 patients treated in an 80-patient study.Metastatic Melanoma PV-10 Trial Results Encouraging Says Drug Company
Medical News Today, 9 June 2009 a phase-3 study of PV-10 as a single agent therapy for patients with locally advanced cutaneous melanoma (Clinical Trials ID NCT02288897) is enrolling patients.Provectus Biopharmaceuticals Reports Data On PV-10 in Combination Therapy and T Cell Mediated Immunity Presented at American Association for Cancer Research (AACR) Annual Meeting 2016. April 2016
/ref> Rose bengal has been shown to not just prevent the growth and spread of ovarian cancer, but also to cause apoptotic cell death of the cancer cells. This has been proven in vitro, in order to prove that rose bengal is still a possible option in the treatment of cancer, and further research should be done. Rose bengal has been used to treat

colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...

. In one such study, a protective immune response was generated from

immunogenic cell death Immunogenic cell death is any type of cell death eliciting an immune response. Both accidental cell death and regulated cell death can result in immune response. Immunogenic cell death contrasts to forms of cell death ( apoptosis, autophagy or othe ...

. Rose bengal is also used in

animal models of ischemic stroke Animal models of ischemic stroke are procedures inducing cerebral ischemia. The aim is the study of basic processes or potential therapeutic interventions in this disease, and the extension of the pathophysiological knowledge on and/or the improveme ...

(photothrombotic stroke models) in biomedical research. A bolus of the compound is injected into the venous system. Then the region of interest (e.g., the cerebral cortex) is exposed and illuminated by LASER light of 561 nm. A thrombus is formed in the illuminated blood vessels, causing a stroke in the dependent brain tissue. Rose bengal has been used for 50 years to diagnose liver and eye cancer. Rose bengal dye is mixed with the homogenate of Brucella and pH of the solution is maintained at 3.8, and this dye is used to diagnose Brucellosis by agglutinating the suspected serum. Rose bengal is slightly irritating and toxic to the eye. It has also been used as an insecticide. Rose bengal is able to stain cells whenever the surface epithelium is not being properly protected by the preocular tear film, because rose bengal has been proven to not be able to stain cells because of the protective functioning of these preocular tear films. This is why rose bengal is often useful as a stain in diagnosing certain medical issues, such as conjunctival and lid disorders. Rose bengal has been used for ocular surface staining to study the efficacy of punctal plugs in the treatment of

keratoconjunctivitis sicca Dry eye syndrome (DES), also known as keratoconjunctivitis sicca (KCS), is the condition of having dry eyes. Other associated symptoms include irritation, redness, discharge, and easily fatigued eyes. Blurred vision may also occur. Symptoms range ...

. Rose bengal is being researched as an agent in creating nano sutures. Wounds are painted on both sides with it and then illuminated with an intense light. This links the tiny collagen fibers together sealing the wound. Healing is faster and the seal reduces chances of infection. Rose bengal is used to suppress bacterial growth in several microbiological media, including Cooke's rose bengal agar. Rose bengal has been used as a protoplasm stain to discriminate between living and dead micro-organisms, particularly

, since the 1950s when

Bill Walton William Theodore Walton III (born November 5, 1952) is an American television sportscaster and former professional basketball player. He played college basketball for coach John Wooden and the UCLA Bruins, winning three consecutive national ...

developed the technique. Rose bengal acetate can act as a

photosensitiser Photosensitizers produce a physicochemical change in a neighboring molecule by either donating an electron to the substrate or by abstracting a hydrogen atom from the substrate. At the end of this process, the photosensitizer eventually returns t ...

and may have potential in

photodynamic therapy Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance, used in conjunction with molecular oxygen to elicit cell death (phototoxicity). PDT is popularly used in treating acne. It is used cl ...

to treat some cancers.

References

External links

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Absorption and extinction data
{{DEFAULTSORT:Rose Bengal Ophthalmology Triarylmethane dyes Phenols Chloroarenes Iodoarenes Spiro compounds VMAT inhibitors Acid dyes