Effects of halogens on European air-quality.

Halogens (Cl, Br) have a profound influence on stratospheric ozone (O3). They (Cl, Br and I) have recently also been shown to impact the troposphere, notably by reducing the mixing ratios of O3 and OH. Their potential for impacting regional air-quality is less well understood. We explore the impact of halogens on regional pollutants (focussing on O3) with the European grid of the GEOS-Chem model (0.25° × 0.3125°). It has recently been updated to include a representation of halogen chemistry. We focus on the summer of 2015 during the ICOZA campaign at the Weybourne Atmospheric Observatory on the North Sea coast of the UK. Comparisons between these observations together with those from the UK air-quality network show that the model has some skill in representing the mixing ratios/concentration of pollutants during this period. Although the model has some success in simulating the Weybourne ClNO2 observations, it significantly underestimates ClNO2 observations reported at inland locations. It also underestimates mixing ratios of IO, OIO, I2 and BrO, but this may reflect the coastal nature of these observations. Model simulations, with and without halogens, highlight the processes by which halogens can impact O3. Throughout the domain O3 mixing ratios are reduced by halogens. In northern Europe this is due to a change in the background O3 advected into the region, whereas in southern Europe this is due to local chemistry driven by Mediterranean emissions. The proportion of hourly O3 above 50 nmol mol-1 in Europe is reduced from 46% to 18% by halogens. ClNO2 from N2O5 uptake onto sea-salt leads to increases in O3 mixing ratio, but these are smaller than the decreases caused by the bromine and iodine. 12% of ethane and 16% of acetone within the boundary layer is oxidised by Cl. Aerosol response to halogens is complex with small (∼10%) reductions in PM2.5 in most locations. A lack of observational constraints coupled to large uncertainties in emissions and chemical processing of halogens make these conclusions tentative at best. However, the results here point to the potential for halogen chemistry to influence air quality policy in Europe and other parts of the world.

2-[4-(4-Methoxyphenylcarbonyloxy)benzylidene]-6-dimethylaminomethyl cyclohexanone hydrochloride: a Mannich base which inhibits the growth of some drug-resistant strains of Mycobacterium tuberculosis.

2-[4-(4-Methoxyphenylcarbonyloxy)benzylidene]-6-dime-thylaminomethyl cyclohexanone hydrochloride 1 has a MIC value of 0.78 microg/mL towards Mycobacterium tuberculosis H37Rv and displays similar or identical MIC figures towards various drug-resistant strains of this microorganism. The enone 1 along with a partial structure 2-dimethylaminomethylcyclohexanone hydrochloride 3 affected respiration in isolated rat liver mitochondria differently which may contribute to the variation in toxicity to both normal cells and M. tuberculosis.

The role of oxidative stress in the development of congestive heart failure in a chicken genotype selected for rapid growth.

The present study examined the possible role of reactive oxygen species in the pathogenesis of heart failure in broilers. Data were collected from three groups of birds at various risk of heart failure: Leghorn chickens (resistant to heart failure), slow-growing feed-restricted broilers (low risk of heart failure), fast-growing ad libitum fed broilers (high risk of heart failure), and broilers with congestive heart failure (CHF). In the first part of the study, basic clinical parameters and ultrastructural changes were examined in the context of lipid peroxidation of the ventricular myocardium. This was followed by the study of in vitro changes in the activity of selected cytosolic enzymes (creatine kinase and lactate dehydrogenase) and mitochondrial enzymes (pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase) in the presence of oxidants (hydrogen peroxide or tertiary butyl hydroperoxide). The distinctive clinical feature in the fast-growing broilers and in the broilers with CHF as compared with slow-growing broilers or Leghorn chickens was a significantly lower heart rate (P <0.05). Electron microscopy revealed marked morphological changes in myocardial mitochondria in these broilers (i.e. fast-growing broilers and broilers with CHF). The level of malondialdehyde equivalents, an indicator of lipid peroxidation subsequent to generated oxidative stress, was significantly higher (P <0.05) in ad libitum fed broilers and was highest (P <0.01) in broilers with CHF. In vitro, the presence of oxidants had a detrimental effect on creatine kinase and alpha-ketoglutarate dehydrogenase activity, while lactate dehydrogenase activity increased. The activity of pyruvate dehydrogenase was not altered by oxidants. Our results indicate that the deterioration of heart function in fast-growing commercial broilers in our experimental model is associated with oxidative stress leading to lipid peroxidation of cellular and mitochondrial membranes, and decreased activity of myocardial creatine kinase and alpha-ketoglutarate dehydrogenase enzymes critical for energy synthesis and transformation pathways.

The effect of some 1-[4-(2-diethylaminoethoxy)phenylcarbonyl]-3,5-bis (benzylidene)-4-piperidone methiodides and related compounds on respiration and swelling of rat liver mitochondria.

The effect of a number of N-aroyl-3,5-bis(benzylidene)-4-piperidones 2 and related quaternary ammonium compounds 3 on the rates of respiration in rat liver mitochondria were determined. All of the compounds stimulated respiration and the greatest effect was displayed by the compounds in series 3 which caused swelling of mitochondria.

Complications of diagnostic carotid/cerebral arteriography when performed by a vascular surgeon.

Carotid stenting has recently been considered as an alternative treatment to carotid endarterectomy for certain patients with carotid stenosis. Hence, performing carotid arteriography with minimal morbidity and mortality is essential. The purpose of this study was to audit complications of diagnostic carotid/cerebral arteriography performed by a vascular surgeon with experience in endovascular interventions. One hundred one consecutive patients underwent 4-vessel arch aortography with selective carotid, subclavian, and/or vertebral arteriography with use of the Seldinger technique. Demographic data, indications, procedure approach (transfemoral, brachial), number of arteries punctured, type of selective injection, contrast volume, and procedure time were analyzed. Minor complications were those that do not significantly alter the health or activity of the patient or require extra hospitalization or treatment. Other complications were defined as major complications. The technical success rate was 99% (100/101 patients). These included the following: 82 patients with right carotid artery, 82 with left carotid artery, 15 with right subclavian artery, 21 with left subclavian artery, 11 with right vertebral artery, and 17 with left vertebral artery (a total of 228 selective injections). Indications for procedures included the following: transient ischemic attack (TIA)/stroke symptoms in 66%, asymptomatic carotid stenosis in 22%, upper limb claudication in 4%, and vertebrobasilar insufficiency in 4%. Right femoral puncture was used in 79%, left femoral in 12%, and left brachial in 9%. The mean amount of contrast used was 101 cc (45-250 cc) and the mean procedure time was 46 minutes (22-132 minutes). There were 5 complications in the whole series: 3 major complications (3%), including 1 minor stroke (1%) with carotid injection, 1 TIA, and 1 major retroperitoneal bleeding; and 2 (2%) minor complications. The major complication rate in this series compares favorably to published rates of 5.7% to 9.1%. There was no association between complications and specific risk factors except for a longer catheterization time (66 minutes versus 45 minutes, p=0.011). Carotid/cerebral arteriography can be done safely by experienced vascular surgeons with minimal perioperative complications that compare favorably with what has been reported in the radiology literature.

Mitochondrial mutations may increase oxidative stress: implications for carcinogenesis and aging?

The sensitivity of mitochondrial DNA to damage by mutagens predisposes mitochondria to injury on exposure of cells to genotoxins or oxidative stress. Damage to the mitochondrial genome causing mutations or loss of mitochondrial gene products, or to some nuclear genes encoding mitochondrial membrane proteins, may accelerate release of reactive species of oxygen. Such aberrant mitochondria may contribute to cellular aging and promotion of cancer.

Effects of metals, ligands and antioxidants on the reaction of oxygen with 1,2,4-benzenetriol.

1,2,4-Benzenetriol is an active metabolite of the human leukemogen benzene that reacts rapidly with molecular oxygen (O2). The mechanism of autoxidation of benzenetriol is scantily characterized, and little is known of the effects of metals, metal chelators, radical scavengers, and antioxidants on the rate of reduction of O2. Here, we report that catalytic amounts of Cu2+ and Fe3+ accelerated the oxidation of benzenetriol (250 mu M) in a dose-dependent manner. Fe3+ (50 mu M) increased the rate of autoxidation by 91%, and Cu2+ (10 mu M) increased it 11-fold. In the absence of added metals, superoxide dismutase inhibited and desferrioxamine stimulated the autoxidation. In the Cu2+ -catalyzed reaction, superoxide dismutase neither inhibited nor stimulated, while desferrioxamine abolished the catalysis by Cu2+. In the presence of Fe3+, superoxide dismutase slowed the reaction, but desferrioxamine, surprisingly, did not. The presence of both superoxide dismutase and desferrioxamine blocked the autoxidation, either in the presence or absence of metals. We conclude: (1) superoxide is a propagator of sequential one-electron transfer reactions in the absence of added metals; (2) addition of Cu2+, unlike Fe3+, removes the dependence of the reaction on propagation by superoxide, presumably changing the radical-propagated chain reaction to a concerted two-electron transfer; (3) the further addition of desferrioxamine restores superoxide-dependent propagation. Taken with our previous data on the genotoxicity of benzenetriol, these findings have implications regarding a role for transition metals in the carcinogenicity of benzene.

Multiple actions of superoxide dismutase: why can it both inhibit and stimulate reduction of oxygen by hydroquinones?

Superoxide dismutase can either inhibit or stimulate autoxidation of different hydroquinones, suggesting multiple roles for O2.-. Inhibitory actions of superoxide dismutase include termination of O2.(-)-propagated reaction chains and metal chelation by the apoprotein. Together, chelation of metals and termination of O2.(-)-propagated chains can effectively prevent reduction of oxygen. Chain termination by superoxide dismutase can thus account for negligible accumulation of H2O2 without invoking a superoxide:semiquinone oxidoreductase activity for this enzyme. One stimulatory action of superoxide dismutase is to decrease thermodynamic limitations to reduction of oxygen. Whether superoxide dismutase inhibits or accelerates an autoxidation depends on the reduction potentials of the quinone and the availability of metal coordination for inner sphere electron transfers.

DNA breakage induced by 1,2,4-benzenetriol: relative contributions of oxygen-derived active species and transition metal ions.

We report here the relative roles of metals and selected reactive oxygen species in DNA damage by the genotoxic benzene metabolite 1,2,4-benzenetriol, and the interactions of antioxidants in affording protection. 1,2,4-Benzenetriol induces scission in supercoiled phage DNA in neutral aqueous solution with an effective dose (ED(50)) of 6.7 microM for 50% cleavage of 2.05 microg/ml supercoiled PM2 DNA. In decreasing order of effectiveness: catalase (20 U/ml), formate (25 mM), superoxide dismutase (20 U/ml), and mannitol (50 mM) protected, from 85 to 28%. Evidently, H(2)O(2) is the dominant active species, with O(2)(*)(-) and *OH playing subordinate roles. Desferrioxamine or EDTA inhibited DNA breakage by 81-85%, despite accelerating 1,2,4-benzenetriol autoxidation. Consistent with this suggestion of a crucial role for metals, addition of cupric, cuprous, ferric, or ferrous ions enhanced DNA breakage, with copper being more active than iron. Combinations of scavengers protected more effectively than any single scavenger alone, with implications for antioxidants acting in concert in living cells. Synergistic combinations were superoxide dismutase with *OH scavengers, superoxide dismutase with desferrioxamine, and catalase with desferrioxamine. Antagonistic (preemptive) combinations were catalase with superoxide dismutase, desferrioxamine with *OH scavengers, and catalase with *OH scavengers. The most striking aspect of synergism was the extent to which metal chelation (desferrioxamine) acted synergistically with either catalase or superoxide dismutase to provide virtually complete protection. Concluding, 1,2,4-benzenetriol-induced DNA damage occurs mainly by site-specific, Fenton-type mechanisms, involving synergism between several reactive intermediates. Multiple antioxidant actions are needed for effective protection.

Modifications in heme iron of free and vesicle bound cytochrome c by tert-butyl hydroperoxide: a magnetic circular dichroism and electron paramagnetic resonance investigation.

To characterize changes to the heme and the influence of membrane lipids in the reaction of cytochrome c with peroxides, we studied the reaction of cytochrome c with tert-butyl hydroperoxide (tert-BuOOH) by magnetic circular dichroism (MCD) and direct electron paramagnetic resonance (EPR) in the presence and absence of different liposomes. Direct low-temperature (11 degrees K) EPR analysis of the cytochrome c heme iron on exposure to tert-BuOOH shows a gradual (180 s) conversion of the low-spin form to a high-spin Fe(III) species of rhombic symmetry (g = 4.3), with disappearance of a prior peroxyl radical signal (g(o) = 2.014). The conversion to high spin precedes Soret band bleaching, observable by UV/Vis spectroscopy and by magnetic circular dichroism (MCD) at room temperature, that indicates loss of iron coordination by the porphyrin ring. The presence of cardiolipin-containing liposomes delayed formation of the peroxyl radical and conversion to high-spin iron, while dicetylphosphate (DCP) liposomes accelerated these changes. Correspondingly, bleaching of cytochrome c by tert-BuOOH at room temperature was accelerated by several negatively charged liposome preparations, and inhibited by mitochondrial-mimetic phosphatidylcholinephosphatidylethanolaminecardiolipin (PCPECL) liposomes. Concomitant with bleaching, spin-trapping measurements with 5,5-dimethyl-1-pyroline-N-oxide showed that while the relative production of peroxyl, alkoxyl, and alkyl radicals was unaffected by DCP liposomes, PCPECL liposomes decreased the spin-trapped alkoxyl radical signal by 50%. The EPR results show that the primary initial change on exposure of cytochrome c to tert-BuOOH is a change to a high-spin Fe(III) species, and together with MCD measurements show that unsaturated cardiolipin-containing lipid membranes influence the interaction of tert-BuOOH with cytochrome c heme iron, to alter radical production and decrease damage to the cytochrome.

DNA-breaking versus DNA-protecting activity of four phenolic compounds in vitro.

Given the paradoxical effects of phenolics in oxidative stress, we evaluated the relative pro-oxidant and antioxidant properties of four natural phenolic compounds in DNA nicking. The phenolic compounds differed dramatically in their ability to nick purified supercoiled DNA, with the relative DNA nicking activity in the order: 1,2,4-benzenetriol (100% nicking) > gallic acid > caffeic acid > gossypol (20% nicking). Desferrioxamine (0.02 mM) decreased DNA strand breakage by each phenolic, most markedly with gallate (85% protection) and least with caffeic acid (26% protection). Addition of metals accelerated DNA nicking, with copper more effective (approximately 5-fold increase in damage) than iron with all four phenolics. Scavengers revealed the participation of specific oxygen-derived active species in DNA breakage. Hydrogen peroxide participated in all cases (23-90%). Hydroxyl radicals were involved (32-85%), except with 1,2,4-benzenetriol. Superoxide participated (81-86%) with gallic acid and gossypol, but not with caffeic acid or 1,2,4-benzenetriol. With 1,2,4-benzenetriol, scavengers failed to protect significantly except in combination. Thus, in the presence of desferrioxamine, catalase or superoxide dismutase inhibited almost completely. When DNA breakage was induced by Fenton's reagent (ascorbate plus iron) the two catechols (caffeic acid and gossypol) were protective, whereas the two triols (1,2,4-benzenetriol and gallic acid) exacerbated damage.

Iron mobilization by succinylacetone methyl ester in rats. A model study for hereditary tyrosinemia and porphyrias characterized by 5-aminolevulinic acid overload.

Accumulation of 5-aminolevulinic acid (ALA) is an event characteristic of porphyrias that may contribute to their pathological manifestations. To investigate effects of ALA independent of porphyrin accumulation we treated rats with the methyl ester of succinylacetone, an inhibitor of 5-aminolevulinic acid dehydratase that accumulates in the porphyric-like syndrome hereditary tyrosinemia. Acute 2-day treatment of fasted rats with succinylacetone methyl ester (SAME) promoted a 27% increase in plasma ALA. This increase in plasma ALA was accompanied by augmentation of the level of total nonheme iron in liver (37%) and brain (20%). Mobilization of iron was also indicated by 49% increase in plasma iron and a 77% increase in plasma transferrin saturation. Liver responded with a mild (12%) increase in ferritin. Under these acute conditions, some indications of oxidative stress were evident: a 15% increase in liver reactive protein carbonyls, and a 42% increase in brain subcellular membrane TBARS. Brain also showed a 44% increase in CuZnSOD activity, consistent with observations in treatment with ALA. Overall, the data indicate that SAME promotes ALA-driven changes in iron metabolism that could lead to increased production of free radicals. The findings support other evidence that accumulation of ALA in porphyrias and hereditary tyrosinemia may induce iron-dependent biological damage that contributes to neuropathy and hepatoma.

A field study of the generation of nitrate in a hill cap cloud.

A field experiment to investigate the formation of nitrate as an airstream passes through a hill cap cloud has been performed at the UMIST field station on Great Dun Fell. It has been shown that the aerosol nitrate concentration increased by about 0.5 microg m(-3) as the airstream passed through the cloud during the night. At sunrise the nitrate production disappeared. It is suggested that the most likely mechanism for this nitrate production was due to the solution of N2O5 and NO3 formed from the reaction of NO2 with O3. These higher oxides build up overnight in the absence of short wave radiation to photolyse them. Other possible mechanisms of nitrate production are also discussed.

A case study: the importance of a dynamic evaluation in the assessment of posterior knee pain.

To evaluate and treat knee problems, it is important to have an understanding of the functional anatomy of the structures about the knee joint. Injuries involving the musculature that insert or originate about the knee can cause pain leading to loss of function. The gastrocnemius muscle, primarily a plantarftexor of the ankle; is also a flexor of the knee joint due to its origin just above the lateral and medial femoral condyles on the posterior surface of the femur.' The following case report is of a strain to the medial head of the gastrocnemius which resulted in pain located at the posteriormedial region of the knee. A differential test to distinguish between a lesion of the gastrocnemius and the posterior capsule of the knee is presented.J Orthop Sports Phys Ther 1983;5(3):132-133.

Adaptation of skeletal muscle to resistance training.

This paper was prepared in partial fulfillment for Doctoral Degree in Physical Therapy at Texas Woman's University in Houston, TX. Resistance training is frequently used in rehabilitation to improve musculoskeletal function. The increased ability of skeletal muscle to generate force following resistance training results from two important changes: 1) the adaptation of the muscle fiber, and 2) the extent to which the motor unit can activate the muscle (neural adaption). The purpose of this article is to provide a review of research investigating the effects of resistance training on muscle fibers and on nervous system input. Muscle fiber adaptations caused by resistance training include increased cross-sectional area of the muscle (hypertrophy, hyperplasia, or both), selective hypertrophy of fast twitch fibers, decreased or maintained mitochondrial number and capillary density of muscle, and possible changes in energy sources. Changes in nervous system input resulting from resistance training include recruitment of an increased number and firing rate of motor units, increased reflex potentiation, and improved synchronization. An understanding of the adaptations occurring in muscle in response to resistance training provides a fundamental basis for which appropriate clinical exercise training programs can be developed for the rehabilitation of patients. J Orthop Sports Phys Ther 1990;12(6):248-255.

Computed tomography versus color duplex ultrasound for surveillance of abdominal aortic stent-grafts.

PURPOSE: To compare the ability of computed tomography (CT) and color duplex ultrasound (CDUS) to detect endoleak and accurately measure aortic aneurysm diameters after endovascular repair. METHODS: Between February 2000 and October 2004, 178 consecutive patients (156 men; mean age 74 years, range 49-89) were treated with aortic stent-grafts (86 Ancure, 55 AneuRx, and 37 Excluder). The follow-up protocol included serial CT and CDUS at 1 month and every 6 months thereafter. Sensitivity, specificity, positive predictive value, negative predictive value, and Kappa statistics (kappa) were calculated using CT as the gold standard; Bland-Altman analysis was used to determine the 95% limits of agreement. Paired and unpaired t tests and correlation coefficients were used to compare the methods. RESULTS: Follow-up ranged from 1 to 53 months (mean 16), during which 367 paired CT and CDUS studies were acquired. The mean diameter of the AAA sac after repair was 5.15 cm by CT versus 4.99 cm by CDUS (p=0.07); 93% of paired studies were somewhat similar (

Interactions between metals, ligands, and oxygen in the autoxidation of 6-hydroxydopamine: mechanisms by which metal chelation enhances inhibition by superoxide dismutase.

Transition metal ions and superoxide participate in different autoxidations to a variable extent. In the reaction of 6-hydroxydopamine (6-OHDA) with oxygen at pH 7.0 or 8.0, addition of 5 to 300 U/ml superoxide dismutase inhibited autoxidation by up to 96% at the highest concentrations. Superoxide dismutase at concentrations of 5-20 U/ml inhibited by less than 40% when present alone, but inhibited by over 99% in the presence of desferrioxamine or histidine. EDTA also enhanced the inhibition by 20 U/ml superoxide dismutase to 86%, even though EDTA accelerated the autoxidation of 6-OHDA when present alone or with desferrioxamine. In contrast, other ligands, such as ADP or phytic acid, had little or no effect on inhibition by superoxide dismutase. Proteins such as albumin, cytochrome oxidase, or denatured superoxide dismutase also enhanced inhibition by active superoxide dismutase from less than 40% to over 90%. Evidently, in the presence of redox active metals, autoxidation occurs by inner sphere electron transfer, presumably within a ternary 6-OHDA.metal.oxygen complex. This mechanism does not involve free O2-. and is not inhibited by superoxide dismutase. On the other hand, the presence of certain ligands (including proteins) diminishes the ability of trace metals to exchange electrons with 6-OHDA or oxygen by an inner sphere mechanism. These ligands render autoxidation dependent on propagation by O2-. and therefore inhibitable by superoxide dismutase. Previously conflicting reports that superoxide dismutase alone inhibits 6-OHDA autoxidation are thus explicable on the basis that at sufficient concentration the apoprotein coordinates trace metals in such a way to preclude inner sphere metal catalysis.

Bioflavonoid rescue of ascorbate at a membrane interface.

In aqueous solution, ascorbate potently prevents bleaching of cytochrome c on exposure to excess H2O2 or t-butyl hydroperoxide. Ascorbate failed to protect cytochrome c in the presence of liposomes of mitochondrial membranelike composition. Like the redox mediator N,N,N,'N'-tetramethyl-p-phenylenediamine (TMPD), however, the bioflavonoids epicatechin and quercetin restored the protection afforded by ascorbate in the presence of liposomes and gave further protection. The quercetin glycoside, rutin, was much less effective, as was the vitamin E analog Trolox. In the presence of liposomes, quercetin alone was relatively ineffective, but cooperated with ascorbate to extend protection synergistically. The results bear specific implications in antioxidant protection of cytochrome c and in moderation of its hydroperoxidase activities in biological membranes. The data also reveal a situation where ascorbate is without effect except in the presence of a bioflavonoid, and substantiate a possibly vital role for certain bioflavonoids in mediating electron transfer from ascorbate into a hydrophobic environment.

Hypothesis: etiology of atherosclerosis and osteoporosis: are imbalances in the calciferol endocrine system implicated?

Atherosclerosis and osteoporosis are currently considered unrelated diseases. Osteoporosis involves bone calcium (Ca) loss and predominantly affects females after menopause. Atherosclerosis is an illness predominantly affecting males, and is primarily characterized by abnormal lipid metabolism. However, pathological calcification of the arterial wall is an underlying feature of atherosclerosis. Ca homeostasis is thus important in atherosclerosis as well as in osteoporosis. Men also develop osteoporosis although at a later age than women, and, as osteoporosis progresses in women, there is an accompanying calcification of arteries leading to increased incidence of atherosclerosis in aging women. Thus, during old age, both atherosclerosis and osteoporosis are prevalent in both males and females. The dramatic increase in atherosclerosis among women as they develop osteoporosis suggests that the two illnesses may be more closely related than previously realized. The use of vitamin D as a food supplement coincides with epidemic onsets of atherosclerosis and osteoporosis, and excess vitamin D induces both conditions in humans and laboratory animals. These observations suggest a role for chronic vitamin D excess in the etiology of the two illnesses. Magnesium (Mg) deficiency, nicotine, and high dietary cholesterol are contributing factors that accentuate adverse effects of vitamin D.

Effects of doxorubicin, 4'-epirubicin, and antioxidant enzymes on the contractility of isolated cardiomyocytes.

The purpose of this study was to determine the acute effects of doxorubicin and its less cardiotoxic epimer, 4'-epirubicin, on the contractile response of isolated myocytes, and to assess similarities or differences with respect to active oxygen-derived mechanisms. Calcium-tolerant myocytes from rat ventricle were field stimulated at 1.0 Hz, and the maximum extent of cell shortening, peak shortening velocity, and peak relaxation velocity of single twitches were measured by video edge detection. The contractile responses of the myocytes to the two anthracyclines were approximately equal. Exposure of the cells to 10 microM of either anthracycline for 20 min decreased all indices of contractility by 28% (p < 0.05). The active oxygen scavengers, superoxide dismutase and catalase, distinguished the extent to which active oxygen was involved in modifying cellular contractility. Paradoxically, superoxide dismutase alone (10 U/mL) decreased contractility by 21%. Nevertheless, superoxide dismutase (10 U/mL) prevented the decreases in contractility produced by doxorubicin. In contrast, superoxide dismutase only mildly (32%) protected against 4'-epirubicin. Catalase (10 U/mL), however, provided substantial (82-93%) protection against both anthracyclines. Hydrogen peroxide therefore, and presumably hydroxyl radicals, were involved in mediating the decreases in contractility from both doxorubicin and 4'-epirubicin. These results show that an acute exposure to clinically relevant concentrations of these anthracyclines significantly depresses myocyte contractility and that, in this respect, 4'-epirubicin is as potentially cardiotoxic as doxorubicin. The results with antioxidant enzymes also strongly support a free radical mechanism for the toxicity of doxorubicin and 4'-epirubicin to cardiomyocytes.