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PubMed1995

Effect of hyperglycaemia on the hepatic metabolism and excretion of xenobiotics.

The biliary excretion of drugs has been investigated in hyperglycaemic male Wistar rats. Hyperglycaemia was produced by a continuous infusion of glucose in different concentrations. To examine the effect of hyperglycaemia on the biliary excretion rate of xenobiotics, one representative of non-metabolizing exogenous organic anions (rose bengal) and metabolizing phenolic drugs (p-nitrophenol) as model compounds were used. A dose-dependent increase of blood and bile glucose level was found after the continuous infusion of glucose in a concentration of 10, 20 or 30%. Biliary flow and biliary excretion of rose bengal were significantly depressed in hyperglycaemic rats. Hepatic conjugation of p-nitrophenol with glucuronic acid appeared to be decreased, however, a compensatory increase of sulphoconjugation of p-nitrophenol was observed in hyperglycaemic rats. Biliary excretion of unconjugated p-nitrophenol was negatively influenced by high blood glucose level and the overall hepatic elimination of p-nitrophenol was also diminished by hyperglycaemia. Insulin (I U/kg i.v.) compensated partly the depressive effect of high blood sugar level on the biliary excretion rate of rose bengal, however, it was unable to abolish completely the negative effects of hyperglycaemia. These results indicate that hyperglycaemia does alter the hepatic elimination of xenobiotics.

Animals↗
PubMed1990

Photosensitizing potential of benzanthrone.

In skin-photosensitization studies on guinea-pigs benzanthrone induced significant erythema and oedema, depending upon the doses both of benzanthrone and of sunlight or artificially simulated UVA radiation. Maximum sensitization and delayed tanning response on the guinea-pig skin were observed 24-36 hr after irradiation. Photosensitized benzanthrone was found to produce significant amounts of singlet oxygen in vitro, as assessed by the bleaching of N,N-dimethyl-p-nitrosoaniline. As with haematoporphyrin and rose bengal, both of which are potent generators of singlet oxygen, the production of singlet oxygen by benzanthrone was dependent on both the concentration of the test chemical and the dose of solar radiation. Benzanthrone also produced a significant yield of superoxide anion radicals on exposure to simulated solar radiation or sunlight. Photosensitized benzanthrone induced photohaemolysis of rat erythrocytes and lipid peroxidation of erythrocyte ghosts, in vitro, probably largely through involvement of singlet oxygen (1O2). The rate of lipid peroxidation by photosensitized benzanthrone was inhibited by 64-80% with 1,4-diazabicyclo(2,2,2)octane and sodium azide, 15% with superoxide dismutase but was not affected by mannitol and sodium benzoate. Equimolar concentrations of haematoporphyrin and rose bengal also produced considerable photohaemolysis of erythrocytes and lipid peroxidation in erythrocyte ghosts; in both cases rose bengal was the most active and benzanthrone the least active of the three compounds.

Animals↗
PubMed1984

Studies on the toxin of Aspergillus fumigatus. XVIII. Photooxidation of asp-hemolysin in the presence of various dyes and its relation to the site of hemolytic activity.

The site of hemolytic activity of a toxin isolated from Aspergillus fumigatus designated Asp-hemolysin was determined by photooxidation techniques. The hemolytic activity of this toxin was strongly inhibited by photooxidation with methylene blue, rose bengal, riboflavin, or eosin G as a sensitizer, whereas crystal violet, hematoxylin, naphthol yellow S, bromothymol blue, methyl orange, and cresol red had no effect. pH dependence of the inactivation with methylene blue was observed in the narrow range of pH values from 7.0 to 8.0, like that of the inactivation with rose bengal or riboflavin. The histidine, cysteine, methionine, tryptophan, and tyrosine content of methylene blue-photooxidized Asp-hemolysin was significantly decreased, while other amino acids were not affected. The hemolytic activity of the toxin was lost more slowly than the histidine residue, being maintained at about 50% even at the time when the histidine residue was completely lost after 30 min. Photooxidation of Asp-hemolysin in the presence of rose bengal also caused a decrease in histidine, methionine, and threonine content. These findings suggest that residues of cysteine, methionine, threonine, tryptophan, and/or tyrosine but not histidine may play an important role through stereostructure in the manifestation of the hemolytic activity of Asp-hemolysin.

Amino Acids↗
PubMed1993

Differential Reactivity of [beta]-Carotene Isomers from Dunaliella bardawil Toward Oxygen Radicals.

Dunaliella bardawil accumulates massive amounts of [beta]-carotene in two isoforms, a 9-cis and an all-trans stereoisomer, when grown under high irradiance, as a means to protect the cells against photoinhibition (A. Ben-Amotz, A. Shaish, M. Avron [1989] Plant Physiol 91: 1040-1043). The purpose of this work has been to find out if the mechanism of protection involves scavenging of reactive oxygen species. For this purpose high- and low-[beta]-carotene-containing cells were compared with respect to their sensitivity to several external oxidants [H2O2, methyl viologen, rose bengal, and 2,2[prime]-azobis(2-amidinopropane)HCl]. All oxidants induce a light-stimulated degradation of [beta]-carotene and of chlorophyll. The degradation of [beta]-carotene precedes that of chlorophyll, indicating that it is more reactive toward oxidants. The 9-cis [beta]-carotene is degraded faster than the all-trans stereoisomer when exposed to oxidants, both in intact cells and in isolated [beta]-carotene globules, indicating that it is a more effective scavenger of reactive oxygen species. Comparison of the sensitivity to different oxidants, between high- and low-[beta]-carotene-containing cells, reveals similar rates of chlorophyll and [beta]-carotene degradation in the two populations. Survival tests toward H2O2 and rose bengal show that high-[beta]-carotene cells have a similar sensitivity toward H2O2 but are more resistant toward rose bengal, a photoactivated generator of singlet oxygen, possibly due to masking of the latter by [beta]-carotene. These results suggest that the protection mechanism of massively accumulated [beta]-carotene in Dunaliella against photoinhibition is not due to scavenging of reactive oxygen species.

Journal Article↗
PubMed2002

[Validation of a questionnaire for the diagnosis of dry eye].

PURPOSE: To develop and evaluate a questionnaire for diagnosis and follow-up of patients with symptoms suggestive of eye surface pathology. To evaluate the efficacy of dry eye treatment. METHODS: Samples were chosen among dry eye patients (n=44). A control group was chosen among the healthy population. The questionnaire was filled in at the beginning and end of the treatment with carbopol + polyvinyl alcohol (Siccafluid, Thea, Spain) four times a day. Initial and final punctuation was established and confronted with other classic diagnostic tests; fluorescein tear break up time, Schirmer test and Rose Bengal staining. RESULTS: Red eyes, lid inflammation, discharge, dry eye, sandy and foreign body sensations, burning, itching, discomfort, pricking, tearing and photophobia got significantly better after treatment (p<0.05). Lid reddening, lid inflammation, flakes in lashes, sticky eyes in the morning, teary eyes, transitory blurring vision and heavy sensation didn't improve (p>0.05). Total punctuation was significantly reduced at one month of treatment (p<0.01). Validation of the test was done against other standard tests (Schirmer test and Rose Bengal). We found a sensitivity of 76% and specificity of 71.5% for Schirmer test and a sensibility of 77% and specificity of 65% if gold standard was Rose Bengal. Predictive value (positive and negative), global value of the test and likelihood ratios were also assessed. CONCLUSION: This questionnaire is useful for diagnosis and follow-up of patients with dry eyes and other ocular surface symptoms. Carbopol + polyvinyl alcohol is useful for the treatment of patients with secretor tear insufficiency.

Acrylic Resins↗
PubMed1988

Swine brucellosis in Indonesia.

Brucella suis biotype 1 was isolated from 13.1% of the pigs slaughtered in Kapuk Jakarta, West Java and from 15.09% of the pigs slaughtered in Surabaya, East Java. The prevalence of B. suis by means of the Rose Bengal Plate Test, was 22.3% for West Java and 14.9% for East Java. The Rose Bengal Plate Test detected more B. suis infected animals (73% of the infected animals) than did the Complement Fixation Test (41%) and the Serum Agglutination Test (54.5%). The high infection rate is a potential health danger for the abattoir workers.

Agglutination Tests↗
PubMedDate not supplied

Effect of punctal occlusion by Freeman silicone plug insertion on tear osmolarity in dry eye disorders.

We retrospectively examined the effect of punctal occlusion by Freeman silicone plug insertion on dry eye disorders in 17 patients. Patients met at least two of the following criteria: history consistent with dry eye, interpalpebral rose bengal staining, and elevated tear film osmolarity. Plug insertion significantly decreased tear film osmolarity. Rose bengal staining decreased in 75% of the eyes examined. There were no cases of postoperative epiphora. Punctal plug insertion is therapeutic for dry eye disease, but extrusion is a significant problem.

Adult↗
PubMed2004

Effect of reverse micelles on the Rose Bengal-sensitized photo-oxidation of 1- and 2-hydroxynaphthalenes.

Benzylhexadecyl dimethylammonium chloride (BHDC) and sodium bis(2-ethylhexyl) sulfosuccinate (AOT) water-in-oil micro-emulsions were employed to study the influence of medium heterogeneity on singlet molecular oxygen [O(2)((1)Delta(g))]-mediated degradation of 1-hydroxynaphthalene (1-OHN) and 2-hydroxynaphthalene (2-OHN) in their naphthoate form. The kinetic study in the micellar system, that was considered as a closer model for the environment of contaminants in natural polluted waters, consisted of a comparative work with the process in homogeneous solution, by varying surfactant structure and water content of the micro-emulsion. While it is known that 1-OHN and 2-OHN are rapidly and efficiently photo-oxidised in aqueous medium, time-resolved phosphorescence detection of O(2)((1)Delta(g)) and stationary photolysis experiments demonstrate that both the values for the overall and reactive rate constants for the quenching of O(2)((1)Delta(g)) and the photo-oxidation efficiencies are lowered in BHDC micelles, whereas the photo-oxidative process in AOT micro-emulsions was totally inhibited. Results are interpreted and discussed on the basis of different locations of the probe in the micellar environment.

Indicators and Reagents↗
PubMed2003

Oral pilocarpine for the treatment of ocular symptoms in patients with Sjögren's syndrome: a randomised 12 week controlled study.

OBJECTIVE: To evaluate the efficacy and side effects of oral pilocarpine for the treatment of ocular symptoms in patients with primary Sjögren's syndrome (SS). METHODS: A 12 week, single centre, randomised controlled study was performed. Twenty nine patients were randomly assigned to receive oral pilocarpine (5 mg twice a day), 28 only artificial tears, and 28 inferior puncta occlusion. Patients receiving oral pilocarpine and those with inferior puncta occlusion also received artificial tears. Patients were evaluated at baseline and throughout the study for their subjective global assessment of dry eyes and for their objective assessment of dry eyes (Schirmer's-I test, rose bengal test, and imprint test). RESULTS: Patients taking oral pilocarpine had significant improvement in subjective global assessment of dry eyes, as was evaluated by improvement of >55 mm on a visual analogue scale (VAS) for responses to the eye questionnaire, compared with patients treated with artificial tears (p<0.001) and those with inferior puncta occlusion (p<0.05). Furthermore, patients receiving oral pilocarpine also showed greater objective improvement, as measured by the rose bengal test (p<0.05), while Schirmer's-I test showed no differences between the treated groups. Commonly reported adverse events were headache, increased sweating, nausea, and vomiting in the pilocarpine group, while one patient in the inferior puncta occlusion group had blepharitis and was withdrawn from the study. CONCLUSION: 10 mg of pilocarpine daily given to patients with SS for 12 weeks had a beneficial effect on subjective eye symptoms, as evaluated by improvement >55 mm on a VAS. Additionally, an improvement of rose bengal staining was noted, but an increase in tear production, as measured by the Schirmer-I test, was not substantiated.

Administration, Oral↗
PubMed2004

Laboratory diagnosis of brucellosis in a rural endemic area in northeastern Spain.

Sera obtained from 62 patients from four mountain counties in Catalonia (Northeastern Spain), in whom brucellosis had been diagnosed on the basis of clinical evidence and/or personal history, were analyzed using the rose Bengal test, standard serum agglutination test (SAT), Coombs' test, ELISA, and complement fixation. The diagnosis was further confirmed through blood cultures. Clinical evidence, epidemiology, and the results from serologic tests were used to assign patients to one of two groups: group 1 (n = 38) patients had primary infections, whereas group 2 (n = 24) patients had been previously exposed to the microorganism, i.e. re-infection of group 2 individuals occurred after long periods of time during which no active infection by Brucella had been detected. Receiving-operating charts (ROC) were used to determine the diagnostic value of the different tests and to establish discriminant values. Blood culture was a valuable diagnostic tool in group 1 (0.92 sensitivity) but was inappropriate in group 2 (0.08). The combination of positive rose Bengal test and agglutination >/=1/160 was valid for diagnosis in group 1. In group 2, agglutination <1/160 (including negative agglutination) did not rule out brucellosis. The combination of positive rose Bengal test and Coombs' test >/=1/320 was the best diagnostic criterion (0.8 specificity; 1 sensitivity). ELISA (for IgG, IgM, or both) did not improve diagnostic accuracy.

Brucellosis↗
PubMed1998

Role of impression cytology during hypovitaminosis A.

AIMS: Evaluation of the morphological damage to the ocular surface of patients operated for biliopancreatic diversion for pathological obesity and the correlation of impression cytology with vitamin A plasma levels, adaptometry, and other general variables. METHODS: 48 patients (15 males, 33 females, age range 21-73) and 34 normal subjects were examined with fluorescein and rose bengal, a plasma dose of vitamin A, and adaptometry. The results of the various tests were subdivided into three levels (0 = normal, 1 = moderately altered, 2 = seriously altered). The impression cytology and adaptometry results were correlated with vitamin A levels and other patient data (age, nutritional condition, time since operation, percentage weight loss). All the examinations were repeated after intramuscular therapy with vitamin A. RESULTS: Corneoconjunctival alterations visible with fluorescein and rose bengal staining were present in 67.7% of cases, impression cytology alterations in 93.7%, adaptometric alterations in 82.2%; vitamin A plasma levels were below normal in 95.8% of cases. After the therapy with vitamin A a significant reduction was found for every examination. The correlation between impression cytology and adaptometry and vitamin A plasma levels and between corneoconjunctival alterations and vitamin A plasma levels was significant. There was no significant correlation between impression cytology and nutritional condition, age time since operation, and percentage weight loss. CONCLUSION: These results show impression cytology is a specific indicator for hypovitaminosis A because it is not influenced by other factors related to the general condition of the patient. Many patients with hypovitaminosis A not demonstrating ocular symptoms of changes visible with fluorescein and rose bengal showed alterations with impression cytology.

Adaptation, Ocular↗
PubMed2002

Sodium hyaluronate eye drops of different osmolarity for the treatment of dry eye in Sjögren's syndrome patients.

AIM: To study the effect of the treatment of dry eye in Sjögren's syndrome patients with hypotonic or isotonic hyaluronate eye drops. METHODS: 40 Sjögren's syndrome patients were divided in two groups and treated as follows: group 1 with hypotonic (150 mOsm/l) 0.4% hyaluronate eye drops; group 2 with isotonic 0.4% hyaluronate eye drops. The eye drops were instilled six times a day for 90 days. Grading of subjective symptoms, break up time (BUT), corneal fluorescein staining, conjunctival rose bengal staining, Schirmer's I test, and conjunctival impression cytology were carried out at 0 and 15, 30, 90 days from the beginning of the study. Patients were examined in a blind fashion. For the statistical analysis the Student's t test, Mann-Whitney U test, and chi(2) test were performed. RESULTS: Symptoms were statistically significantly improved at day 15 in both groups but group 1 patients had a global score statistically significantly better group 2 (p=0.02). At day 15 group 1 patients had an improvement from baseline values of BUT (p=0.003), fluorescein, and rose bengal score (p=0.000001 and p=0.0004 respectively). Group 2 patients had, at day 15, an improvement of BUT and fluorescein score compared to baseline values (p=0.05 and p=0.0001 respectively). A comparison between the two groups showed better results for group 1 patients at day 15 for rose bengal stain (p=0.01) and for BUT (p=0.05) and fluorescein score (p=0.0003) at day 90. The conjunctival impression cytology showed that group 1 had a statistically significant better total score than group 2 starting from day 15 and lasting throughout the study (p<0.02). Also group 2 patients showed an improvement from baseline values starting from day 30 (p=0.000005). CONCLUSION: Hyaluronate eye drops are useful for treating severe dry eye in Sjögren's syndrome patients. The use of a formulation with pronounced hypotonicity showed better effects on corneoconjunctival epithelium than the isotonic solution.

Adult↗
PubMed2005

Tear clearance measurement in patients with dry eye syndrome using quantitative lacrimal scintigraphy.

OBJECTIVE: The aim of this study was to evaluate the tear clearance in patients with dry eye syndrome using quantitative lacrimal scintigraphy. MATERIALS AND METHODS: We investigated 21 patients (42 eyes; 18 women, 3 men; mean age, 63.19 +/- 13.33 years) with dry eye syndrome. Additionally, for the sake of comparison, 12 normal subjects of the same age group (24 eyes; 10 women, 2 men; mean age, 68.25 +/- 2.63 years) were included. Lacrimal scintigraphy, Schirmer-1 test, BUT, and rose bengal ocular surface vital staining were performed in these cases. RESULTS: According to the results of lacrimal scintigraphy, the mean value of T 1/2 was 4.16 +/- 1.22 minutes and the mean value of RI was 14.15% +/- 2.30% in normal subjects. However, in patients with dry eye syndrome, these values were 20.59 +/- 1.97 minutes and 55.64% +/- 6.90%, respectively. Consistent with the results of ophthalmologic tests, the mean Schirmer-1 value was 12.46 +/- 2.10 mm, the mean value of BUT was 14.36 +/- 3.40 seconds, and the mean staining value of the rose bengal was 1.98 +/- 0.80 in normal subjects, whereas these values were 1.36 +/- 0.49 mm, 5.46 +/- 1.33 seconds, 6.62 +/- 0.86, respectively, in patients with dry eye syndrome. When we compared the results of lacrimal scintigraphy and the results of ophthalmologic tests, an inverse correlation was noted between both the T1/2 and RI values and both the Schirmer-1 and BUT values in all subjects (p < 0.001). However, there was a greater positive correlation between the rose bengal ocular surface staining value and both the T1/2 and RI values in all cases (p < 0.001). CONCLUSION: In the current study, it was concluded that although the lacrimal drainage system was normal, tear clearance was significantly delayed in dry eye patients. With this study, we have shown that quantitative lacrimal scintigraphy, which is an objective, practical, and noninvasive method, appears to be useful for the assessment of the tear clearance in patients with dry eye syndrome.

Aged↗
PubMed2006

Assessment of serological response of young and adult sheep to conjunctival vaccination with Rev-1 vaccine by fluorescence polarization assay (FPA) and other serological tests for B. melitensis.

The serological response of young and adult sheep vaccinated conjunctivally with Rev-1 vaccine was assessed by fluorescence polarization assay (FPA), Rose Bengal test (RBT), complement fixation test (CFT), modified Rose Bengal test (m-RBT), indirect ELISA (i-ELISA) and competitive ELISA (c-ELISA), at different post vaccination intervals. One hundred and thirty six adult sheep and 64 lambs were used in the study. The vaccinated animals were bled prior to vaccination (0 day) and thereafter at 21st, 42nd, 35th, 63rd, 91st, 125th, 159th, and 223rd and 330th day post vaccination. The majority of animals (young and adult) showed positive reaction by FPA, RBT, CFT, m-RBT and c-ELISA 21 days post vaccination, whereas by i-ELISA at 42 days. All tests perform equal when animals vaccinated as young are tested 125 days (4 months) post vaccination. In case of animals vaccinated at adulthood, FPA, RBT, CFT and c-ELISA perform equal if the animals are tested 223 days (approximately 8 months) post vaccination. I-ELISA and m-RBT show low specificity if ewes vaccinated at adulthood are tested 330 days (11 months) post vaccination. If control of brucellosis in sheep is based on conjunctivally vaccination of lambs with Rev-1, the vaccinated animals can be tested by any test used for diagnosis of B.melitensis infection accurately at least 4 months post vaccination. If brucellosis control is based on mass vaccination the use of m-RBT and i-ELISA is not recommended for testing adult animals at least for 330 days (11 months) post vaccination due to tests low specificity. Further research is needed so the appropriate cut-offs to be established for FPA, c-ELISA or i-ELISA to become valuable tools for the eradication of Brucella spp. infection in small ruminants in areas where vaccination is practiced.

Animals↗
PubMed1999

In vivo antioxidant activity of genistein in a murine model of singlet oxygen-induced cerebral stroke.

We evaluated the in vivo antioxidant activity of genistein in a mouse model of singlet oxygen-induced cerebral stroke. Cerebral stroke was induced in male BALB/c mice through extensive microvessel damage caused by photoactivated rose bengal dye. The photoactivation of the intravenously administered rose bengal was achieved by transcranial illumination with green light. Genistein was more active than its analogs and other antioxidants that were used as control agents. At a dose of 16 mg/kg genistein administered every 6 h from 24 h prior to irradiation until 24 h after irradiation, the average size of the cerebral lesion of genistein-treated mice was significantly smaller than that in control mice treated with the carrier DMSO (8.1 +/- 1.0 mm(2) compared to 14.6 +/- 0.7 mm(2), P < 0.001). Our findings provide experimental evidence that genistein could be useful for the prevention of cerebral stroke and other pathological conditions caused by reactive oxygen species.

Animals↗
PubMed2000

Two phases of gramicidin photoinactivation in bilayer lipid membranes in the presence of a photosensitizer.

The kinetics of the light-induced decrease in the gramicidin-mediated current across a bilayer lipid membrane in the presence of a photosensitizer has been shown to include a slow phase with a characteristic time of the order of 1 s and a fast phase. Based on the dependence of the slow phase relative amplitude and characteristic time on the gramicidin-mediated stationary conductance we concluded that the slow phase reflected the establishment of an equilibrium between gramicidin monomers and dimers in the membrane after the distortion of this equilibrium resulting from modification of a portion of gramicidin molecules by reactive oxygen species generated upon excitation of the photosensitizer. The dependence of the fast phase contribution to the overall kinetics on the stationary conductance allowed us to conclude that the fast phase is associated with transition of gramicidin dimers into a nonconducting state. The characteristic time of the fast phase measured with nanosecond laser excited pulses is 1.5 ms. The slow phase of the decrease in the gramicidin-mediated current was considerably decelerated in the presence of Rose Bengal. The results obtained indicate that adsorption of Rose Bengal on the bilayer interface leads to a reduction of the dipole potential drop at the membrane-solution boundary, similarly to the action of phloretin.

Gramicidin↗
PubMed1972

The role of histidine residues in glutamate dehydrogenase.

1. Glutamate dehydrogenase was subject to rapid inactivation when irradiated in the presence of Rose Bengal or incubated in the presence of ethoxyformic anhydride. 2. Inactivation in the presence of Rose Bengal led to the photo-oxidation of four histidine residues. Oxidation of three histidine residues had little effect on enzyme activity, but oxidation of the fourth residue led to the almost total loss of activity. 3. Acylation of glutamate dehydrogenase with ethoxyformic anhydride at pH6.1 led to the modification of three histidine residues with a corresponding loss of half the original activity. Acylation at pH7.5 led to the modification of two histidine residues and a total loss of enzyme activity. 4. One of the histidine residues undergoing reaction at pH6.1 also undergoes reaction at pH7.5. 5. The presence of either glutamate or NAD(+) in the reaction mixtures at pH6.1 had no appreciable effect. At pH7.5 glutamate caused a marked decrease in both the degree of alkylation and degree of inactivation. NAD(+) had no effect on the degree of inactivation at pH7.5 but did modify the extent of acylation. 6. The normal response of the enzyme towards ADP was unaffected by acylation at pH6.1 or 7.5. 7. The normal response of the enzyme towards GTP was altered by treatment at both pH6.1 and 7.5.

Acylation↗
PubMed1991

Functional and electrophysiological effects of oxidant stress on isolated ventricular muscle: a role for oscillatory calcium release from sarcoplasmic reticulum in arrhythmogenesis?

STUDY OBJECTIVE: The aim was to investigate the cellular basis of oxidant stress induced arrhythmias by studying the influence of oxidant stress on the contractile and electrophysiological function of isolated cardiac muscle. DESIGN: Oxidant stress was induced by the photoactivation of rose bengal added to the solution superfusing isolated ventricular muscles from a number of species. Measurements of contractile and electrophysiological function were made under control conditions, during exposure to oxidant stress, and under a number of experimental conditions. EXPERIMENTAL MATERIAL: Isolated superfused papillary muscles or trabeculae from rat, rabbit, or frog hearts were used in all studies. MEASUREMENTS AND MAIN RESULTS: The contractile response to oxidant stress was assessed by measuring isometric developed tension and resting tension throughout the experiment, and the electrophysiological response was assessed by recording action potentials using conventional 3 M KCl filled intracellular electrodes. Oxidant stress induced a transient positive inotropy, after-contractions, and eventually contracture. Associated with these contractile changes were prolongation of the action potential, early afterdepolarisations, oscillations in resting membrane potential, and automaticity. These effects were concentration and species dependent and the oscillations in both tension and membrane potential were abolished by inhibition of calcium release from the sarcoplasmic reticulum with caffeine. CONCLUSIONS: The contractile and electrophysiological effects of rose bengal induced oxidant stress are consistent with a cellular calcium overload. The observation that the oscillations in tension and membrane potential were abolished by caffeine and that these effects were species dependent (rat greater than rabbit greater than frog) suggests a role for oscillatory sarcoplasmic reticulum calcium release in these effects. The oscillations in membrane potential and the automaticity induced by rose bengal are likely to underlie the arrhythmias observed in isolated hearts exposed to oxidant stress that have previously been described.

Animals↗