Niveles glutatión reducido y estado redox celular en pacientes pediátricos con inmunodeficiencias / Reduced glutathione levels and cellular redox status in pediatric patients with immunodeficiencies

Introducción: Las alteraciones en el estado redox celular se han descrito como factores causales en diversas enfermedades. La depleción del glutatión reducido se ha asociado fundamentalmente a enfermedades neurodegenerativas, pulmonares, hepáticas, cardiovasculares e inmunológicas. Objetivo: Determinar las concentraciones de glutatión reducido y el estado redox celular en pacientes pediátricos con inmunodeficiencias. Métodos: Se estudiaron 21 pacientes con inmunodeficiencias procedentes de la consulta de Inmunogenética, en edades comprendidas entre 1 y 8 años, de ambos sexos, y 8 niños en el mismo rango de edad de los pacientes, como grupo control, con estudios de inmunidad humoral y celular normales. Los pacientes con diagnóstico de inmunodeficiencia se dividieron para su estudio en 2 grupos según el componente afectado de la respuesta inmune: humoral y celular. Fueron determinadas las concentraciones intraeritrocitarias de glutatión reducido y oxidado, mediante un método de HPLC-UV. Para evaluar el estado redox celular se calculó la relación entre las formas reducidas y oxidadas del glutatión (GSH/GSSG). Resultados: Las concentraciones de glutatión reducido y el estado redox celular se encontraron disminuidos en ambos grupos de pacientes en relación con los niños sin inmunodeficiencia (p=0,031 y p=0,03; respectivamente). El glutatión oxidado no mostró diferencias entre los grupos. Conclusiones: En los pacientes con inmunodeficiencia se evidenció la afectación del estado redox celular como consecuencia de la disminución del glutatión reducido. Este primer acercamiento ofreció las potencialidades del empleo de estos biomarcadores en la evaluación integral de pacientes con inmunodeficiencia(AU)

Introduction: Alterations in the cellular redox state have been described as causal factors in various diseases. Reduced glutathione depletion has been fundamentally associated with neurodegenerative, pulmonary, liver, cardiovascular and immunological diseases. Objective: To determine the concentrations of reduced glutathione and the cellular redox status in pediatric patients with immunodeficiencies. Methods: We studied 21 patients with immunodeficiencies from the immunogenetic service, aged between 1 and 8 years and as a control group, 8 children in the same age range as the patients, with normal humoral and cellular immunity studies. Patients diagnosed with immunodeficiency were divided into two groups according to the affected component of the immune response: humoral and cellular. The intraerythrocyte concentrations of oxidized and reduced glutathione were determined by means of an HPLC-UV method. To evaluate the cellular redox state, the relationship between the reduced and oxidized forms of glutathione (GSH/GSSG) was calculated. Results: Reduced glutathione concentrations and cellular redox status were found to be decreased in both groups of patients in relation to children without immunodeficiency (p=0,031 and p=0,03; respectively). Oxidized glutathione showed no difference between the groups. Conclusions: In patients with immunodeficiency, the cellular redox state is affected as a consequence of the decrease in reduced glutathione. This first approach offers the potential for the use of these biomarkers in the comprehensive evaluation of patients with immunodeficiency(AU)

Effects of Higher Doses of Vitamin E on Toxicity and Inflammation

High doses of vitamin E close to the upper limit of toxicity (UL) but still recommended and considered as harmless and beneficial, can possibly cause a number of adverse effects. In a 14-day study, in which male mice were exposed to intra peritoneal doses of 100 and 200 mg vitamin E (alpha-tocopherol)/kg bw/day, biomarkers of oxidative stress related processes (ROM, TTL), and biomakers of tissue toxicity (ALP, ALT, AST, LDH) and inflammation (MCP-1, IL-6, TNF-α, PAI-1 and resistin) were determined. Oxidative stress parameters in plasma did not change, whereas some biomarkers of inflammation were statistically significantly higher on exposure to vitamin E. In the liver, beneficial effects on tissue biomarkers were observed, whereas the inflammation biomarkers showed an U-shaped relation with the dose of vitamin E. In the kidney, the biomarkers of tissue damage showed mixed effects, whereas a substantial increase in the inflammation biomarkers was observed. In the brain, the biomarkers of tissue toxicity showed beneficial effects, whereas the inflammatory biomarkers showed an increase or an U-shaped behaviour with increasing doses of vitamin E. Especially, a dose of 200 mg of vitamin E/kg bw/day showed a number of adverse effects in several tissues. These results confirm our previous study in male mice with exposure of vitamin E by feed. Since the dose of 200 mg of vitamin E/kg bw/day is lower than the upper limit for vitamin E, the UL should be re-evaluated, in view of the effects in kidney and brain.

Flow cytometry detection of cellular redox status with genetically encoded fluorescent probe / 上海交通大学学报（医学版）

Objective: To test the application of flow cytometry technique to detect the redox status with genetically encoded fluorescent probe roGFP2, to compare it with laser scanning confocal microscope (LSCM), and to demonstrate the diversity of cellular redox status in HeLa and Panc-1 cell populations. Methods: Time lapse imaging with LSCM was performed in single cell transfected with roGFP2 probe to detect the dynamic changes of 405 nm/488 nm ratio (405/488 ratio). Flowcytometry technique was also performed in HeLa cells transfected with roGFP2 probe to detect the dynamic alterations of 405/488 ratio. The global cell population was analyzed and the subpopulations of different redox status were dissected. Flowcytometry technique was further applied in Panc-1 cells with different CD24 or CD44 marker to detect the dynamic alterations of 405/488 ratio of roGFP2 and identify the different redox status. Results: Time lapse imaging with LSCM showed that 405/488 ratio of roGFP2 dramatically changed in response to H2O2 in dose and time dependent manner at a single cell level. When dozens of cells were chosen, the average ratio showed increased and dynamic trend. Compared to LSCM, flow cytometry could detect the average of 405/488 ratio of roGFP2 as well. Meanwhile, with the application of flow cytometry the cell population can be divided into three subpopulations based on 405/488 ratios, most in oxidized and medium redox status, few in reduced status. Using flow cytometry, CD24+/CD44+ Panc-1 cells, pancreatic cancer stem cells, can be found to have overall lower 405/488 ratio and more percentage of subpopulation of reduced status under resting and stress condition. Conclusion: Flow cytometry technique can be applied to detect roGFP2 and has advantage in application to show the overall as well as diverse redox status in cell population. Flow cytometry detection of cellular redox status with genetically encoded probe can be a useful tool in tumor cell biology and developmental biology research.

Flow cytometry detection of cellular redox status with genetically encoded fluorescent probe / 上海交通大学学报（医学版）

Objective·To test the application of flow cytometry technique to detect the redox status with genetically encoded fluorescent probe roGFP2,to compare it with laser scanning confocal microscope (LSCM),and to demonstrate the diversity of cellular redox status in HeLa and Pane-1 cell populations.Methods·Time lapse imaging with LSCM was performed in single cell transfected with roGFP2 probe to detect the dynamic changes of 405 nm/488 nm ratio (405/488 ratio).Flowcytometry technique was also performed in HeLa cells transfected with roGFP2 probe to detect the dynamic alterations of 405/488 ratio.The global cell population was analyzed and the subpopulations of different redox status were dissected.Flowcytometry technique was further applied in Panc-1 cells with different CD24 or CD44 marker to detect the dynamic alterations of 405/488 ratio of roGFP2 and identify the different redox status.Results·Thne lapse imaging with LSCM showed that 405/488 ratio of roGFP2 dramatically changed in response to H2O2in dose and time dependent manner at a single cell level.When dozens of cells were chosen,the average ratio showed increased and dynamic trend.Compared to LSCM,flow cytometry could detect the average of 405/488 ratio of roGFP2 as well.Meanwhile,with the application of flow cytometry the cell population can be divided into three subpopulations based on 405/488 ratios,most in oxidized and medium redox status,few in reduced status.Using flow cytometry,CD24+/CD44+ Panc-1 ceils,pancreatic cancer stem ceils,can be found to have overall lower 405/488 ratio and more percentage of subpopulation of reduced status under resting and stress condition.Conclusion·Flow cytometry technique can be applied to detect roGFP2 and has advantage in application to show the overall as well as diverse redox status in cell population.Flow cytometry detection of cellular redox status with genetically encoded probe can be a useful tool in tumor cell biology and developmental biology research.

Inflammatory cytokines and plasma redox status responses in hypertensive subjects after heat exposure

Hypertension is characterized by a pro-inflammatory status, including redox imbalance and increased levels of pro-inflammatory cytokines, which may be exacerbated after heat exposure. However, the effects of heat exposure, specifically in individuals with inflammatory chronic diseases such as hypertension, are complex and not well understood. This study compared the effects of heat exposure on plasma cytokine levels and redox status parameters in 8 hypertensive (H) and 8 normotensive (N) subjects (age: 46.5±1.3 and 45.6±1.4 years old, body mass index: 25.8±0.8 and 25.6±0.6 kg/m2, mean arterial pressure: 98.0±2.8 and 86.0±2.3 mmHg, respectively). They remained at rest in a sitting position for 10 min in a thermoneutral environment (22°C) followed by 30 min in a heated environmental chamber (38°C and 60% relative humidity). Blood samples were collected before and after heat exposure. Plasma cytokine levels were measured using sandwich ELISA kits. Plasma redox status was determined by thiobarbituric acid reactive substances (TBARS) levels and ferric reducing ability of plasma (FRAP). Hypertensive subjects showed higher plasma levels of IL-10 at baseline (P<0.05), although levels of this cytokine were similar between groups after heat exposure. Moreover, after heat exposure, hypertensive individuals showed higher plasma levels of soluble TNF receptor (sTNFR1) and lower TBARS (P<0.01) and FRAP (P<0.05) levels. Controlled hypertensive subjects, who use angiotensin-converting-enzyme inhibitor (ACE inhibitors), present an anti-inflammatory status and balanced redox status. Nevertheless, exposure to a heat stress condition seems to cause an imbalance in the redox status and an unregulated inflammatory response.

Effects of chelated Zn/Cu/Mn on redox status, immune responses and hoof health in lactating Holstein cows

To evaluate the effects of chelated Zn/Cu/Mn on redox status, immune responses and hoof health in lactating Holstein cows, 48 head in early lactation were divided into healthy or lame groups according to their gait score. Cows were fed the same amount of Zn/Cu/Mn as sulfate salts or in chelated forms for 180 days, and foot-and-mouth disease (FMD) vaccine was injected at day 90. The results showed that lame cows had lower antioxidant function, serum Zn/Mn levels, hair Cu levels, and hoof hardness. Moreover, increased antioxidant status, FMD antibody titers, serum and hair levels of Zn/Cu/Mn, and hoof hardness and decreased milk fat percent and arthritis biomarkers were observed in cows fed chelated Zn/Cu/Mn. In summary, supplementation with chelated Zn/Cu/Mn improved antioxidant status and immune responses, reduced arthritis biomarkers, and increased accumulation of Zn/Cu/Mn in the body and hoof hardness in dairy cows.

Estado redox materno en el tercer trimestre de la gestación y su relación con el flujo útero-placentario / Maternal redox state in the third trimester of pregnancy and its relationship with uteroplacental flow

Introducción: durante la gestación el óxido nítrico liberado por las células endoteliales de las arterias uterinas y la vasculatura umbilical promueve la vasodilatación y facilitan el flujo sanguíneo al feto. Los factores prooxidantes pueden, por el contrario, causar disfunción endotelial y comprometer el flujo útero-placentario. Objetivo: determinar la relación entre el estado redox materno en el tercer trimestre de la gestación y el flujo útero-placentario. Métodos: se realizó un estudio observacional analítico, que incluyó a 65 gestantes de las áreas de salud del municipio Bayamo, en el período comprendido desde diciembre de 2011 hasta abril de 2012. Se midió el índice de pulsatilidad promedio de las arterias uterinas y de la arteria umbilical por flujometría doppler, así como, biomarcadores del estado redox en sangre materna: se midió el Potencial Reductor Férrico del suero, la concentración sérica del malondialdehído más el 4-hidroxinonenal, de la vitamina C, la albúmina, el ácido úrico y la de glutatión reducido eritrocitario. Resultados: la mayoría de los índices de pulsatilidad promedio de las arterias uterinas y el de la umbilical se encontraron entre el percentil 95 y 50 para la edad gestacional. Los valores del malondialdehído más el 4-hidroxinonenal como indicadores de daño oxidativo fueron bajos, mientras que se detectaron altos valores de la vitamina C, del glutatión reducido y de la actividad de la enzima superóxido dismutasa. Las concentraciones de la vitamina C se asociaron de manera directa y significativa con el índice de pulsatilidad promedio de las arterias uterinas. Conclusiones: se concluye que el comportamiento de los biomarcadores del estado redox se corresponde con un adecuado estado antioxidante y con el estado del flujo útero-placentario, no obstante, a que solo las concentraciones de la vitamina C se asociaron con este.

Introduction: during gestational stage, nitric oxide released by placenta endothelial cells, uterine arteries, and umbilical vasculature promote vasodilatation and facilitate blood flow to the fetus. Pro-oxidant factors may, however, cause endothelial dysfunction and compromise the uterus-placentary flow. Objective: to determine the relationship between maternal redox status in the 3rd. trimester of pregnancy and uterus-placental flow. Methods: a prospective observational study was performed; it included 65 pregnant women from Bayamo municipality from December 2011 to April 2012. The average pulsatility index of the uterine arteries and umbilical artery using Doppler flowmetry, as well as redox status biomarkers in maternal blood were measured: Ferric reducing potencial, Serum malondialdehyde plus 4-hydroxynonenal, vitamin C, albumin, uric acid, and erythrocyte reduced glutathione concentration were measured. Total extracellular superoxide dismutase and catalase activity were also measured. Results: most of the average pulsatility index of the uterine and cord arteries was found between the 95 and 50 percentile for gestational age. Malondialdehyde values plus 4-hydroxynonenal were low, whereas high values were detected from vitamin C, reduced glutathione and the superoxide dismutase enzyme activity. Vitamin C concentrations were directly and significantly associated with mean pulsatility index of the uterine arteries. Conclusions: the behavior of redox status biomarkers corresponds to an adequate antioxidant status and the state of, however, only the concentrations of vitamin C were associated with uterus-placental flow.

Trigonella foenum graecum and Saliva aegyptiaca modulates hepatic redox status in Ehrlich-ascites-carcinoma-bearing mice.

The present study was carried out to assess the effect of plant's extract on Ehrlich ascites carcinoma (EAC) and its influence on redox status and tissue injury on liver. Among five groups of albino mice, three were treated with plant's extract, in addition, a group treated with the standard drug, 5-fluorouracil. Ascites tumor was introduced into female mice by inoculation of 2.5 x 106 viable tumor cells/mouse. After 5 days of transplantation, the extraction of Saliva aegyptiaca (Egyptian sage) and Trigonella foenum graecum (fenugreek) were given daily for 4 days via intraperitoneal route at a dose level of 55 and 100 mg/kg body weight, respectively, to mice bearing EAC cells. The results revealed that both Egyptian sage and fenugreek normalized oxidative stress in liver of mice-bearing EAC cells evidenced by increasing the level of glutathione. On the other hand, significant decreases in the levels of malondialdehyde and nitric oxide were demonstrated in liver indicating controlled oxidative stress in these animals. As a consequence, Egyptian sage and fenugreek regulated liver enzymes namely alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase and total bilirubin. Regarding to histopathological results, treatment with Egyptian sage and fenugreek extracts diminished most of the pathological alterations induced by EAC cells in mice. In conclusion, the present data suggested that Egyptian sage and fenugreek as a potential therapeutic complement in the treatment of different pathologies that may be related to an imbalance of the cellular oxidoreductive status associated with liver injury.

Curcumin sensitizes lung adenocarcinoma cells to apoptosis via intracellular redox status mediated pathway.

The present study demonstrates that curcumin acts as pro-oxidant and sensitizes human lung adenocarcinoma epithelial cells (A549) to apoptosis via intracellular redox status mediated pathway. Results indicated that curcumin induced cell toxicity (light microscopy and MTT assay) and apoptosis (AnnexinV-FITC/PI labeling and caspase-3 activity) in these cells. These events seem to be mediated through generation of reactive oxygen species (ROS) and superoxide radicals (SOR) and enhanced levels of lipid peroxidation. These changes were accompanied by increase in oxidized glutathione (GSSG), reduced glutathione (GSH) and -glutamylcysteine synthetase (-GCS) activity, but decrease in GSH/GSSG ratio. The induction of apoptosis and decrease in GSH/GSSG ratio was also accompanied by sustained phosphorylation and activation of p38 mitogen activated protein kinase (MAPK). On the other hand, addition of N-acetyl cysteine (NAC), an antioxidant, blocked the curcumin-induced ROS production and rescued malignant cells from curcumin-induced apoptosis through caspase-3 deactivation. However, L-buthionine sulfoximine (BSO), a GSH synthesis blocking agent, further enhanced curcumin-induced ROS production and apoptosis in A549 cells. Decreased GSH/GSSG ratio seems to be a crucial factor for the activation of MAPK signaling cascade by curcumin. The study therefore, provides an insight into the molecular mechanism involved in sensitization of lung adenocarcinoma cells to apoptosis by curcumin.

Determinants of oxidative stress and DNA damage (8-OhdG) in squamous cell carcinoma of head and neck.

Background: Squamous cell carcinoma of head and neck (SCCHN) is a major concern of health risk in developing countries, such as India. Apart from genetic configuration, environmental and lifestyle factors, as well as poor oral hygiene, provide free radical-generating environment, which may contribute to the development of cancer through DNA damage. Materials and Methods: Here we ascertained the various oxidative stress determinants in diagnosed SCCHN patients with health risk addictions. This study further evaluated the incremental effects inflicted by these lifestyle factors on redox status. The study included 100 consenting SCCHN patients and 90 matched healthy controls. Salivary total antioxidant capacity (TAC), glutathione (GSH), free radicals: such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) along with oxidative DNA adduct (8-OHdG) were monitored. Results: Our findings indicated altered salivary oxidant-antioxidant status in SCCHN. A substantial rise in ROS (~2.0 folds) and RNS (~1.4 folds), together with significant lowering in TAC (~1.2 folds) and GSH (~1.7 folds) was observed. The 8-OHdG levels were also found to be considerably higher (P < 0.001) in salivary cell's DNA of these patients. Conclusions: Our results demonstrate significant redox imbalance in cancer patients suggesting their paramount importance in the development of SCCHN.

A influência do metabolismo redox na transmissão da doença de Chagas / The influence of the redox metabolism upon the transmission of Chagas disease

As formas epimastigotas de Trypanosoma cruzi proliferam e se diferenciam no interior de diferentes compartimentos do trato digestivo dos triatomíneos. Esses ambientes antagônicos, no que diz respeito à concentração de nutrientes, pH e status redox, constituem um desafio para o protozoário por conterem moléculas e fatores capazes de deflagrar diferentes sinalizações e respostas no parasito. Por isso, testamos a influência de produtos abundantes do metabolismo do vetor e de status redox distintos, frente aos processos de proliferação e diferenciação in vivo e in vitro. Como exemplo temos o heme e a hemozoína, subprodutos da digestão da hemoglobina, e o urato, rico na urina dos insetos. O heme é uma importante molécula em todos os seres vivos. Nosso grupo mostrou seu papel na proliferação in vitro de T. cruzi e que esse sinal é governado pela enzima redox-sensível CaMKII (Lara et al., 2007; Souza et al., 2009). Esse efeito parece depender de uma sinalização redox, onde o heme e não seus análigos induz a formação de EROs, modulando a atividade da CaMKII (Nogueira et al, 2011). Apesar de gerar espécies reativas de oxigênio (EROs) em formas epimastigotas, o heme não alterou a ultraestrutura desses parasitos mostrando uma adaptação a ambientes oxidantes. Além disso, a adição de FCCP inibiu a formação de EROs mitocondrial, diminuindo a proliferação dos parasitos. Em contrapartida, a AA aumentou drasticamente a produção de EROs mitocondrial levando à morte dos epimastigotas. Estes resultados confirmam a hipótese de regulação redox do crescimento de epimastigotas...

Trypanosoma cruzi epimastigotes proliferate and differentiate inside different compartments of the triatomines gut. These environments are antagonic in terms of nutrient content, pH and redox status. All these factors represent a challenge to the protozoan due to the presence of molecules and factors which are able to induce different signals to the parasite. Thus, we tested the influence of abundant metabolism products of the vector, with distinct redox status, in the proliferation and metacyclogenesis in vitro and in vivo. These molecules are heme and hemozoin, both byproducts of hemoglobin digestion, and urate, present in the urine of insects. Heme is a ubiquitous molecule present in all living organisms. Our group studied its role in T. cruzi growth in vitro, showing that this signal is governed by the redox-sensitive enzyme CaMKII (Lara et al., 2007; Souza et al., 2009). Indeed, it seems to rely on a redox signaling pathway in which heme, but not its analogs, induces ROS formation, thus modulating CaMKII activity (Nogueira et al., 2011). Although it induces ROS in epimastigotes, the heme molecule had no deleterious effect upon the parasites ultrastructure, suggesting an adaptation to oxidative environments. In addition, FCCP inhibited mitochondrial ROS formation, then decreasing the parasite proliferation. On the other hand, AA drastically increased mitochondrial ROS production leading to cell death. These results corroborate the hypothesis of redox regulation of epimastigotes proliferation. Hemozoin (β- hematin) formation is an elegant strategy to minimize the toxic effect of heme in hematophagous insects. However, β-hematin had no influence upon the proliferation or metacyclogenesis in vitro. Also, urate, GSH and NAC impaired epimastigote proliferation. These effects were partially reversed when the antioxidants were incubated along with heme...

Changes of plasma redox status in patients with coronary heart disease and its clinical implcations / 中国综合临床

Objective To explore the changes of plasma redox status in patients with coronary heart disease and its clinical implications. Methods One hundred and forty-four patients suspected with coronary heart disease were divided into three groups according to the results of coronary arteriography. Coronary heart disease group (n= 59, group A), coronary atherosclerosis group (n=53, group B), and normal coronary group (n=32, group C). The plasma glutathione (reduced form GSH and oxidized form GSSG) ,oxidized low density hpoprotein cholesterol(ox-LDL-C) and malondialdehyde (MDA) were measured in all patients. The GSH/GSSG redox potential were calculat-ed according to Nernst equation,and their correlation with the severity of coronary artery stenosis and oxLDL-C was analyzed. Results Along with the severity of coronary artery stenosis (from Group C to Group A), GSH, GSH/ GSSG gradually reduced (respectively (321.27±56.80)μmol/L, (309.52±44.97) μmol/L, ( 285.71±38.38) μmol/L;10.56±1.70,9.86±1.58,8.65±1.18 ;F=29.49 and 26.18,P<0.05), whereas GSH/GSSG redox po-tential gradually increased ( (- 142.23±1.35) mV, (-140.41±1.13) mV, (-136.61±1.21 ) mV;F =20.69,P <0.05 )) and redox status deviated to oxidization. The products of oxidative stress oxLDL-C and MDA also increased significantly along with the severity of coronary artery stenosis (respectively (417.24±126.64 ) μg/L, (557.45±171.85) μg/L, (691.96±203, 56 ) μg/L;(2.39±1.24) μmol/L, (3.25±1.37 ) μmol/L, (4.39± 1.52) μmol/L;F=26.28 and 25.39,P<0.05). GSH/GSSG redox potential was positively correlated with oxLDL-C (r=0.798,P<0.05). Conclusions The imbalance of plasma redox status and deviating to oxidization may be closely related with the development and progress of atherosclerosis.

RELATIONSHIP BETWEEN OXIDATION OF MYOFIBRILLAR PROTEINS AND CONTRACTILE PROPERTIES IN SOLEUS MUSCLES FROM HYPERTHYROID RAT / 体力科学

We tested the hypothesis that a force reduction in soleus muscles from hyperthyroid rats would be associated with oxidative modification of myofibrillar proteins. Daily injection of thyroid hormone [3, 5, 3’-triiodo-_L-thyronine (T₃)] for 21 days depressed isometric forces in whole soleus muscle across a range of stimulus frequencies (1, 10, 20, 40, 75 and 100 Hz) (<i>P</i><0.05). In fiber bundles, hyperthyroidism also led to pronounced reductions (<i>P</i><0.05) in both K⁺- and 4-chloro-<i>m</i>-cresol-induced contracture forces. The degrees of the reductions were similar between these two contractures. These reductions in force production were accompanied by a remarkable increment (103% ; <i>P</i><0.05) in carbonyl groups comprised in myofibrillar proteins. In additional experiments, we have also tested the efficacy of carvedilol, a non-selective β₁-β₂-blocker that possesses anti-oxidative properties. Treatment with carvedilol prevented T₃-induced oxidation of myofibrillar proteins. However, carvedilol did not improve the hyperthyroid-induced reductions in force production. These data suggest that oxidative modification of myofibrillar proteins may not account for the reductions in force production of hyperthyroid rat soleus muscle.