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PubMed1993

Photodynamic inactivation of infectivity of human immunodeficiency virus and other enveloped viruses using hypericin and rose bengal: inhibition of fusion and syncytia formation.

The mechanism of the antiviral activity of hypericin was characterized and compared with that of rose bengal. Both compounds inactivate enveloped (but not unenveloped) viruses upon illumination by visible light. Human immunodeficiency and vesicular stomatitis viruses were photodynamically inactivated by both dyes at nanomolar concentrations. Photodynamic inactivation of fusion (hemolysis) by vesicular stomatitis, influenza, and Sendai viruses was induced by both dyes under similar conditions (e.g., I50 = 20-50 nM for vesicular stomatitis virus), suggesting that loss of infectivity resulted from inactivation of fusion. Syncytium formation, between cells activated to express human immunodeficiency virus gp120 on their surfaces and CD4+ cells, was inhibited by illumination in the presence of 1 microM hypericin. Hypericin and rose bengal thus exert similar virucidal effects. Both presumably act by the same mechanism--namely, the inactivation of the viral fusion function by singlet oxygen produced upon illumination. The implications of this photodynamic antiviral action for the potential therapeutic usefulness of both hypericin and rose bengal are discussed.

Animals↗

PubMed2002

Localization of rose bengal, aluminum phthalocyanine tetrasulfonate, and chlorin e6 in the rabbit eye.

PURPOSE: The localization and site of action of photosensitizers in the eye may be important for photodynamic therapy for fundus disorders but remain poorly understood for most agents. We investigated the intraocular localization of xanthene, phthalocyanine, and chlorin photosensitizers by using fluorescence microscopy and digital fundus fluorescence angiography. METHODS: Rose bengal (40 mg/kg), aluminum phthalocyanine tetrasulfonate (CASPc) (5 mg/kg), or chlorin e6 (2 mg/kg) was intravenously administered to albino rabbits. The eyes were enucleated and examined by means of fluorescence microscopy 5, 20, 60, and 120 minutes and 24 hours after dye injection. In vivo digital fundus fluorescence angiography with use of rose bengal (2-4 mg/kg), CASPc (2 mg/kg), and chlorin e6 (2 mg/kg) was performed. RESULTS: For all agents studied pathologically, there was moderate fluorescence from the choroid and retinal pigment epithelium 5 minutes after dye injection. Mild fluorescence detected from the photoreceptor outer segments at 5 minutes was increased at 20 minutes. Angiographic studies with use of rose bengal, CASPc, and chlorin e6 revealed differences in the pattern and rate of photosensitizer accumulation. CONCLUSIONS: Rose bengal, CASPc, and chlorin e6 accumulate rapidly in the choroid and retinal pigment epithelium and less rapidly in the outer retina. Differences in ocular localization of these photosensitizers were demonstrated. The significance of these findings for potential photodynamic therapy with these agents requires further investigation.

Animals↗

PubMed1993

Effect of sodium orthovanadate on the hepatobiliary clearance of rose bengal in streptozotocin-induced diabetic rats.

Sodium orthovanadate is known to promote glucose uptake in muscle and adipose tissues and has been suggested as a possible oral hypoglycemic agent. In addition, insulin-dependent diabetes has been shown to alter the hepatobiliary clearance of several drugs in rats. This study has determined whether orthovanadate, like insulin, can reverse diabetes-induced changes in the biliary excretion of endogenous bile acids and in the hepatobiliary clearance of rose bengal. Six groups of male Sprague-Dawley rats were used; normal, insulin-treated normal, vanadate-treated normal, diabetic, insulin-treated diabetic, and vanadate-treated diabetic. Diabetes was induced by injection of streptozotocin (45 mg/kg, i.v.). One week later, insulin (2-4 U/day, s.c.) and sodium orthovanadate (877 +/- 82 mumol/kg/day, p.o.) treatments were initiated. After 4 weeks, the clearance and biliary excretion of rose bengal (60 mumol/kg, i.v.) were determined for 3 hr. Bile flow rate, rose bengal excretion, and excretion of endogenous bile acids were unchanged in the two treated normal groups and in the insulin-treated diabetic rats. These parameters were increased in untreated diabetic and vanadate-treated diabetic rats as compared with normal. Pharmacokinetic analyses indicated that total and biliary clearances of rose bengal were increased in diabetic rats and that orthovanadate did not reverse these changes. However, liver weight and serum glucose concentrations were reduced by orthovanadate treatment. These data indicate that the oral insulinomimetic chemical sodium orthovanadate effectively reversed some, but not all, of the diabetes-induced alterations of hepatic function.

Animals↗

PubMed1981

Rose bengal induced corneal swelling: relation to inciting wavelength.

Cornea endothelial cells sensitized with rose bengal and exposed to light demonstrated a wavelength dependent alteration in physiological response. Corneas exposed to 549 millimicron swelled at rates similar to controls exposed to identical energy levels of incandescent light. Corneas exposed to 451, 500, 612, and 651 millimicron swelled at rates less rapid than corneas exposed to similar energy levels of incandescent light. The photodynamically induced physiological alteration of cornea endothelial cells approximately paralleled the spectral curve of rose bengal with its peak at 550 millimicron.

Animals↗

PubMed1975

Iodine-123-Rose bengal: An improved hepatobiliary imaging agent.

A practical method for preparing )23-I-rose bengal that allows for its rapid and efficient incorporation into the molecule is reported. Administration of 123-I-rose bengal to normal healthy patients showing the normal uptake and excretory pattern visualized with this radio pharmaceutical is also presented. The overall reduction in imaging time and radiation exposure together with the improved images possible should greatly improve our diagnostic capabilities in evaluating the jaundiced patient.

Humans↗

PubMed1997

Hepatobiliary excretion of bile acids and rose bengal in streptozotocin-induced and genetic diabetic rats.

Divergent opinions regarding the effect of streptozotocin- (STZ) induced diabetes on bile flow rate may be due to the differing lengths of time after STZ administration at which bile flow was measured. Also, the biliary excretion of bile acids can influence the canalicular transport of several organic anions. Therefore, the hepatic clearance of the bile acid-dependent organic anion rose bengal was studied over a 30-day period in STZ-induced insulin-dependent Sprague-Dawley diabetic rats with elevated bile acid pools and in fatty noninsulin-dependent diabetic and lean Wistar rats. Excretion of total bile acids and rose bengal was higher in diabetic rats than in Sprague-Dawley control or lean or fatty Wistar rats. Depletion of bile acids for 10 hr in the 30-day STZ rat prevented the increased excretion of rose bengal. Bile flow rates in fatty and lean Wistar rats were similar to that in Sprague-Dawley controls. Increased bile acid excretion 7 and 14 days after STZ was not accompanied by the expected significant increase in bile flow, reflecting decreased bile acid-independent bile flow, regardless of method of calculation of bile flow (per g liver or per kg body weight). By 30 days, there were significant increases in bile acid excretion and bile flow. The increased clearance of rose bengal 7 days after STZ indicates that pathophysiological changes in the hepatocyte begin soon after the initiation of diabetes. Studies of taurocholate uptake into liver plasma membrane vesicles indicated that the maximal velocity of transport across the basolateral membrane was increased with no change in Km. This change was not observed in vesicles from insulin-treated diabetic rats. Therefore, studies employing STZ need to allow time for STZ toxicity to be overcome and for the pathology of diabetes to become established, to accurately reflect the diabetic condition.

Adenosine Triphosphate↗

PubMed1988

Inhibition of the mitochondrial F1-ATPase by rose bengal mediated photooxidation. Interaction of the Fe2+ chelate of bathophenanthroline with the sensitizer.

Rose Bengal mediated photooxidation of mitochondrial F1-ATPase and its beta-subunit resulted in inactivation and loss of about 50 and 60% of their histidine residues, respectively. The beta-subunit was not cleaved upon photooxidation. Photooxidation of histidine probably results in changes in the conformational stability of F1-ATPase leading to its inactivation. The participation of singlet molecular oxygen during the photooxidation process is suggested by the selective loss of histidine residues, while other amino acids, also sensitive to singlet oxygen attack, were not affected. Photochemical damage of F1-ATPase was prevented by various phenanthroline compounds, the order of efficiency being bathophenanthroline-Fe chelate greater than bathophenanthroline greater than orthophenanthroline-Fe chelate greater than bathophenanthroline-sulfonate-Fe chelate. The prevention by bathophenanthroline-Fe chelate of photochemical damage is interpreted on the basis of its interaction with the photosensitizer, Rose Bengal, probably implying a chemical reaction which decreases the actual concentration of the sensitizer and, thereby, the extent of photoinactivation.

Amino Acids↗

PubMed1988

Quantitative rose bengal staining technique for external ocular diseases.

A new technique for quantitative assessment of rose bengal staining in ocular surface disorders is described. The globe is divided into 16 quadrants which represent clinically important regions of the eye. Each quadrant is graded numerically for intensity and area of rose bengal staining. This simple grading system facilitates mathematical study and computer analysis of ocular surface disease.

Diagnosis, Computer-Assisted↗

PubMed1997

Correlation of goblet cell density and mucosal epithelial membrane mucin expression with rose bengal staining in patients with ocular irritation.

PURPOSE: This study was designed to compare goblet cell densities and mucosal epithelial membrane mucin (MEM) expression in impression cytology specimens obtained from control subjects and patients with one of the following clinically defined diseases: aqueous tear deficiency (ATD) associated with Sjögren syndrome, ATD not associated with Sjögren syndrome, inflammatory Meibomian gland disease associated with rosacea, and Meibomian gland atrophy. These data were correlated with ocular surface rose Bengal staining scores, Schirmer scores, and HLA-DR antigen staining of conjunctival epithelial cells. METHODS: Goblet cell density and MEM expression were studied by impression imprints with immunohistochemical staining using an anti-mucosal epithelial membrane mucin antibody in the temporal and inferior bulbar and inferior tarsal conjunctiva of study subjects. RESULTS: Goblet cell density adjacent to the temporal limbus was significantly reduced at 3 mm posterior to the temporal limbus in both aqueous tear deficiency groups compared with the other groups and in patients with Sjögren syndrome compared with all other groups. In the inferior tarsus, goblet cell density was significantly reduced in patients with non-Sjögren syndrome ATD as compared with all other groups, except those with inflammatory Meibomian gland disease. Mucosal epithelial membrane mucin expression in the bulbar and tarsal conjunctiva was absent in a greater percentage of patients with Sjögren syndrome compared with all other groups. Total ocular surface rose Bengal staining scores were significantly higher in patients with Sjögren syndrome as compared with all other groups and in patients with non-Sjögren syndrome ATD as compared with control groups. Rose Bengal staining scores and Schirmer I test results (without anesthesia) were inversely correlated with bulbar, but not tarsal, conjunctival goblet cell densities, and with the absence of bulbar conjunctival MEM expression. CONCLUSIONS: These results suggest that reduced goblet cell density and mucosal epithelial cell mucin expression could explain increased rose Bengal staining in patients with aqueous tear deficiency. In addition, MEM may be regarded as a marker for normal differentiation of ocular surface epithelia, with its absence signifying the development of squamous metaplasia.

Adult↗

PubMed1999

Inactivation of sunflower NADH:nitrate reductase by white light-activated rose bengal.

Chemical modification of purified nitrate reductase (NR) from sunflower leaves by white light-irradiated rose bengal was studied. NADH:NR activity was inhibited by light-activated rose bengal in both a concentration- and time-dependent manner. MV:NR activity was less sensitive to inhibition than NADH:NR activity, especially when the enzyme was preincubated with NADH. Preincubation of the enzyme with FAD protected inhibition of NADH:NR activity but not the MV:NR activity. These results suggest that sunflower NR contains sensitive histidine residue which interacts with reduced FAD during catalytic electron transfer. Most importantly, NADH-reduced NR was more sensitive to the irradiated dye, indicating that conformation of the oxidized and reduced enzyme forms were different.

Dose-Response Relationship, Drug↗

PubMed1995

Hepatic transport of rose bengal by perfused rabbit liver: the effect of albumin binding on the unidirectional rate constants.

The effect of albumin on the unidirectional rate constants for the hepatic transport of rose bengal was studied using perfused rabbit livers. Rabbit livers were perfused in a recirculating system with albumin concentrations between 10 and 600 microM and the disappearance of I-125 rose bengal following a bolus injection was recorded. A distributed model of hepatic transport was used to estimate the rate constants for influx into cells, efflux from cells to plasma and biliary excretion. When the rate constants were corrected for albumin binding, the influx, but not the efflux or excretion constant, was a steeply rising function of the perfusate albumin concentration. The result that the influx but not efflux constant is albumin dependent suggests that the phenomenon is not due to slow diffusion across an unstirred fluid layer or to nonequilibrium binding within such a layer. The possibility that the albumin-dependent influx is due to a direct exchange of rose bengal between albumin and a membrane carrier protein is also considered. The independence of the efflux constant and the albumin concentration makes this hypothesis less tenable. However, these data are consistent with the facilitation of albumin-ligand dissociation by liver cells. This analysis represents the first reduction to practice of distributed modeling of disappearance curves. The fact that the excretion constant is independent of the perfusate albumin concentration serves to validate the model that has previously only been considered on theoretical grounds.

Animals↗

PubMedDate not supplied

Evaluation of tear break-up time, Schirmer's-I test and rose bengal staining as confirmatory tests for keratoconjunctivitis sicca.

The tear break-up time (BUT), Schirmer's I test (S-I) and slit lamp examination after rose Bengal staining (RBS) are simple tests for evaluation of keratoconjunctivitis sicca (KCS). Discrepancies, however, regarding the range of normal values and the specificity and sensitivity of these methods prompted us to reevaluate them in 81 primary Sjögren's syndrome patients (Ss) and 276 normal volunteers. In normal volunteers, BUT values ranged from 4 sec. to 32 sec. (means +/- SD: 13 +/- 6 sec.) and in primary Ss from 1 sec. to 15 sec. (means +/- SD: 7 +/- 3 sec.). Ninety five percent (95%) of the values from primary Ss patients were below 12 sec. Forty two percent (42%) of the values obtained from normal individuals fall within this range. Schirmer's I test values in normal individuals ranged from 0 mm/5 min. to 30 mm/5 min. (means +/- SD: 10 +/- 9 mm) and in primary Ss patients from 0 mm/5 min. to 30 mm/5 min. (means +/- SD: 4 +/- 7 mm.). Ninety five percent (95%) of the primary Ss patients' values were below 19 mm/5 min. Sixty eight percent (68%) of the normal individual values fall into this range. Rose Bengal staining values ranged in normals from 0 to 7 (means +/- SD: 1 +/- 1) and in primary Ss patients from 1 to 8 (means +/- SD: 5 +/- 2). Ninety five percent (95%) of the primary Ss patients' values were above 2. Only 7% of normal individual values fall into this range. From these data we conclude that rose Bengal staining is the best test for evaluation of keratoconjunctivitis sicca.

Adolescent↗

PubMed1991

131I-rose bengal therapy in hepatoblastoma patients.

If conventional treatment modalities have failed in hepatoblastoma patients and no distant metastases can be demonstrated therapy with radionuclide agents can be considered. In 6 patients diagnostic technetium-99m (99mTc)-disofenin and two iodine-131 (131I)-rose bengal scans were made. 2 patients demonstrated specific uptake of disofenin. One of these had a positive scintigram with radiolabelled rose bengal. This patient was subsequently treated with 1.1 GBq 131I-rose bengal. No toxicity was observed. A clear decrease in the level of alpha-fetoprotein indicated a response and demonstrated that this radiopharmaceutical can be used for tumour targeted radiation therapy in selected patients with therapy resistant tumours.

Carcinoma, Hepatocellular↗

PubMed1954