Differential expression on mitochondrial tryparedoxin peroxidase (mTcTXNPx) in Trypanosoma cruzi after ferrocenyl diamine hydrochlorides treatments

Abstract Resistance to benznidazole in certain strains of Trypanosoma cruzi may be caused by the increased production of enzymes that act on the oxidative metabolism, such as mitochondrial tryparedoxin peroxidase which catalyses the reduction of peroxides. This work presents cytotoxicity assays performed with ferrocenyl diamine hydrochlorides in six different strains of T. cruzi epimastigote forms (Y, Bolivia, SI1, SI8, QMII, and SIGR3). The last four strains have been recently isolated from triatominae and mammalian host (domestic cat). The expression of mitochondrial tryparedoxin peroxidase was analyzed by the Western blotting technique using polyclonal antibody anti mitochondrial tryparedoxin peroxidase obtained from a rabbit immunized with the mitochondrial tryparedoxin peroxidase recombinant protein. All the tested ferrocenyl diamine hydrochlorides were more cytotoxic than benznidazole. The expression of the 25.5 kDa polypeptide of mitochondrial tryparedoxin peroxidase did not increase in strains that were more resistant to the ferrocenyl compounds (SI8 and SIGR3). In addition, a 58 kDa polypeptide was also recognized in all strains. Ferrocenyl diamine hydrochlorides showed trypanocidal activity and the expression of 25.5 kDa mitochondrial tryparedoxin peroxidase is not necessarily increased in some T. cruzi strains. Most likely, other mechanisms, in addition to the over expression of this antioxidative enzyme, should be involved in the escape of parasites from cytotoxic oxidant agents.

Involvement of Src tyrosine kinase and protein kinase C in the expression of macrophage migration inhibitory factor induced by H2O2 in HL-1 mouse cardiac muscle cells

Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, plays an important role in the pathogenesis of atrial fibrillation; however, the upstream regulation of MIF in atrial myocytes remains unclear. In the present study, we investigated whether and how MIF is regulated in response to the renin-angiotensin system and oxidative stress in atrium myocytes (HL-1 cells). MIF protein and mRNA levels in HL-1 cells were assayed using immunofluorescence, real-time PCR, and Western blot. The result indicated that MIF was expressed in the cytoplasm of HL-1 cells. Hydrogen peroxide (H2O2), but not angiotensin II, stimulated MIF expression in HL-1 cells. H2O2-induced MIF protein and gene levels increased in a dose-dependent manner and were completely abolished in the presence of catalase. H2O2-induced MIF production was completely inhibited by tyrosine kinase inhibitors genistein and PP1, as well as by protein kinase C (PKC) inhibitor GF109203X, suggesting that redox-sensitive MIF production is mediated through tyrosine kinase and PKC-dependent mechanisms in HL-1 cells. These results suggest that MIF is upregulated by HL-1 cells in response to redox stress, probably by the activation of Src and PKC.

High passage numbers induce resistance to apoptosis in C2C12 muscle cells

Cell lines with high passage numbers exhibit alterations in cell morphology and functions. In the present work, C2C12 skeletal muscle cells with either low (<20) or high (>60) passage numbers (identified as l-C2C12 or h-C2C12, respectively) were used to investigate the apoptotic response to H2O2 as a function of culture age h-C2C12. We found that older cultures (h-C2C12 group) were depleted of mitochondrial DNA (mtDNA). When we analyzed the behavior of Bad, Bax, caspase-3 and mitochondrial transmembrane potential, we observed that cells in the h-C2C12 group were resistant to H2O2 induction of apoptosis. We propose serially cultured C2C12 cells as a refractory model to H2O2-induced apoptosis. In addition, the data obtained in this work suggest that mtDNA is required for apoptotic cell death in skeletal muscle C2C12 cells.

Glutathione levels in and total antioxidant capacity of Candida sp. cells exposed to oxidative stress caused by hydrogen peroxide / Níveis de glutationa e capacidade antioxidante total em células de Candida sp. expostas a estresse oxidativo causado por peróxido de hidrogênio

INTRODUCTION: The capacity to overcome the oxidative stress imposed by phagocytes seems to be critical for Candida species to cause invasive candidiasis. METHODS: To better characterize the oxidative stress response (OSR) of 8 clinically relevant Candida sp., glutathione, a vital component of the intracellular redox balance, was measured using the 5,5'-dithiobis-(2-nitrobenzoic acid (DTNB)-glutathione disulfide (GSSG) reductase reconversion method; the total antioxidant capacity (TAC) was measured using a modified method based on the decolorization of the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic) acid radical cation (ABTS*+). Both methods were used with cellular Candida sp. extracts treated or not with hydrogen peroxide (0.5 mM). RESULTS: Oxidative stress induced by hydrogen peroxide clearly reduced intracellular glutathione levels. This depletion was stronger in Candida albicans and the levels of glutathione in untreated cells were also higher in this species. The TAC demonstrated intra-specific variation. CONCLUSIONS: Glutathione levels did not correlate with the measured TAC values, despite this being the most important non-enzymatic intracellular antioxidant molecule. The results indicate that the isolated measurement of TAC does not give a clear picture of the ability of a given Candida sp. to respond to oxidative stress.

INTRODUÇÃO: A capacidade de suportar o estresse oxidativo imposto por fagócitos parece ser crítica para que espécies de Candida causem candidíase invasiva. MÉTODOS: Para melhor caracterizar a resposta ao estresse oxidativo (REO) de oito Candida sp. clinicamente relevantes, um componente vital do balanço redox intracelular, a glutationa, foi mensurada pelo método de reconversão DTNB-GSSG redutase e a capacidade antioxidante total (CAT) foi mensurada por um método modificado baseado na descoloração do ABTS*+. Ambos os métodos foram utilizados em extratos celulares das espécies de Candida tratadas ou não com peróxido de hidrogênio (0,5mM). RESULTADOS: O estresse oxidativo induzido pelo peróxido de hidrogênio claramente reduziu os níveis intracelulares de glutationa. Esta diminuição foi mais intensa em C. albicans e os níveis de glutationa em células não tratadas foram também maiores nesta espécie. A capacidade antioxidante total demonstrou variação intraespecífica na capacidade antioxidante. CONCLUSÕES: Os níveis de glutationa não se correlacionaram com a capacidade antioxidante total mensurada, apesar desta ser a defesa antioxidante intracelular não-enzimática mais importante. Os resultados indicam que a medição isolada da CAT não fornece um quadro claro da habilidade de certa espécie de Candida responder ao estresse oxidativo.

In vitro oxidant effects of D-glucosamine reduce adhesión and biofilm formation of Staphylococcus epidermidis / Los efectos oxidantes de la D-glucosamina in vitro reducen la adhesión y formación de biofilms de Staphylococcus epidermidis

Staphylococcus epidermidis is a common pathogen in medical device-associated infections. Its major pathogenic factor is the ability to form adherent biofilms. In this work, three S. epidermidis strains isolated from infected catheters were chosen with the objective of investigating the effect of D-glucosamine (D-Glu) on reactive oxygen species (ROS) production, adhesion and biofilm formation. The chemiluminescence and nitroblue tetrazolium reduction assays were used to determine ROS production by planktonic S. epidermidis and the microtiter plate assay to quantify in vitro biofilm formation. D-Glu generated a dose-dependent increase in ROS in planktonic cells with maximum stimuli at a concentration of 0.05 mM, and reduced adhesion and biofilm formation. On the other hand, glucose showed an antioxidative stress action and promoted biofilm adhesion and growth. This study suggests a potential application of D-Glu against infections associated with indwelling medical devices, since the oxidative stress caused by this hexosamine in planktonic S. epidermidis contributed to reducing biofilm formation.

Staphylococcus epidermidis es un patógeno común en infecciones asociadas a dispositivos médicos. Su factor de patogenicidad más importante es la capacidad para formar biofilms. Se trabajó con tres cepas de S. epidermidis aisladas de catéteres, con las que se efectuaron ensayos de quimioluminiscencia y de reducción de azul de nitrotetrazolio, para determinar la producción de especies reactivas del oxígeno (ERO) en S. epidermidis planctónico, y ensayos dirigidos a cuantificar la formación de biofilm in vitro, empleando placas multipocillos. La D-glucosamina generó un aumento dependiente de la dosis en la producción de ERO en las células planctónicas, con un estímulo máximo a una concentración de 0,05 mM. Este aumento condμlo a la reducción de la adhesión y de la formación de biofilm. La adición de glucosa, en cambio, mostró un efecto anti estrés oxidativo y promovió la adhesión y el crecimiento de biofilm. Este estudio sugiere una posible aplicación de la D-glucosamina contra las infecciones asociadas a dispositivos médicos, ya que el estrés oxidativo provocado por esta hexosamina contribuyó a una menor formación de biofilm.

DNA degradation by aqueous extract of Aloe vera in the presence of copper ions.

The plant Aloe vera has long been used in medicine, as dietary supplements and for cosmetic purposes. Aloe vera extracts are a rich source of polyphenols, such as aloin and aloe emodin and have shown a wide range of pharmacological properties, including anti-inflammatory and anti-cancer properties. The bioactive component aloe emodin has been reported to induce apoptosis in various cancer cell lines. Many of the biological activities of Aloe vera have been attributed to its antioxidant properties. However, most plant-derived polyphenols that are also present in Aloe vera may exhibit pro-oxidant properties either alone or in the presence of transition metals, such as copper. Previous reports from this laboratory have implicated the pro-oxidant action as one of the mechanisms for their anti-cancer properties. In the present paper, we show that aqueous extract of Aloe vera is also able to cause DNA degradation in the presence of copper ions. Further, the extract is also able to reduce Cu(II) to Cu(I) and generate reactive oxygen species, such as superoxide anion and hydroxyl radicals in a dose-dependent manner, which correlates with ability of the extract to cause DNA breakage. Thus, the study shows that in addition to antioxidant activity, Aloe vera extract also possess pro-oxidant properties, leading to oxidative DNA breakage.

Neurotoxicity Screening in a Multipotent Neural Stem Cell Line Established from the Mouse Brain

Neural stem cells (NSCs) have mainly been applied to neurodegeneration in some medically intractable neurologic diseases. In this study, we established a novel NSC line and investigated the cytotoxic responses of NSCs to exogenous neurotoxicants, glutamates and reactive oxygen species (ROS). A multipotent NSC line, B2A1 cells, was established from long-term primary cultures of oligodendrocyte-enriched cells from an adult BALB/c mouse brain. B2A1 cells could be differentiated into neuronal, astrocytic and oligodendroglial lineages. The cells also expressed genotypic mRNA messages for both neural progenitor cells and differentiated neuronoglial cells. B2A1 cells treated with hydrogen peroxide and L-buthionine-(S,R)-sulfoximine underwent 30-40% cell death, while B2A1 cells treated with glutamate and kainate showed 25-35% cell death. Cytopathologic changes consisting of swollen cell bodies, loss of cytoplasmic processes, and nuclear chromatin disintegration, developed after exposure to both ROS and excitotoxic chemicals. These results suggest that B2A1 cells may be useful in the study of NSC biology and may constitute an effective neurotoxicity screening system for ROS and excitotoxic chemicals.

Oxidant stress due to non ionic low osmolar contrast medium in rat kidney.

Background & objectives: Contrast media may cause contrast-induced nephropathy (CIN) in risk group. This study was taken up to establish possible effects of non ionic low osmolar contrast medium administration on oxidant/antioxidant status and nitric oxide (NO) levels in rat kidney tissues. Methods: Fourteen female, 14 wk old Wistar-albino rats were divided into 2 groups of 7 rats each (control and contrast groups). Non ionic low osmolar contrast medium was administered iv to the animals in the contrast group. The day after, animals were sacrificed and malondialdehyde (MDA) and NO levels and activities of antioxidant [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)] and oxidant [xanthine oxidase (XO)] enzymes were measured in kidney tissues. Serum creatinine levels were measured to evaluate kidney functions. Results: Contrast medium administration caused an increase in MDA levels and a decrease in NO levels in kidney tissues. Interpretation & conclusions: The results suggest that non ionic low osmolar contrast medium administration leads to accelerated oxidant reactions and decreased NO level in rat kidney tissues. Further studies need to be done to assess the role of these changes in CIN.

In vitro antifungal action of different substances over microwaved-cured acrylic resins

OBJECTIVE: The presence of Candida albicans on the surfaces of denture-base acrylic resins is strongly related to the development of oral stomatitis. This study evaluated the antifungal action of different agents over microwave-cured acrylic resin without polishing specimens previously contaminated with Candida albicans. MATERIAL AND METHODS: Sixty specimens were immersed in BHI broth previously inoculated with the yeast and stored for 3 h at 37ºC. They were divided into 5 experimental groups (n=10): G1: 2 percent chlorhexidine solution (10 min); G2: 0.5 percent sodium hypochlorite (10 min); G3: modified sodium hypochlorite (10 min); G4: effervescent agent (5 min); G5: hydrogen peroxide 10v (30 min). The specimens of the control group 1 (C1) were not disinfected. Ten additional specimens of the control group 2 (C2) were not infected with the yeast, aiming to check the asepsis during the experiment. The disinfection agents were neutralized and the acrylic resin specimens were immersed in BHI Broth for 24 h. Culture media turbidity was evaluated spectrophotometrically according to the transmittance degree, i.e. the higher the transmittance the stronger the antimicrobial action. Statistical analysis was performed (Kruskal-Wallis Test, p<0.05). RESULTS: The results, represented by the medians, were: G1 = 40; G2 = 100; G3 = 100; G4 = 90; G5 = 100; C1 = 40; C2 = 100. CONCLUSIONS: This in vitro study suggested that sodium hypochlorite-based substances and hydrogen peroxide are more efficient disinfectants against C. albicans than 2 percent chlorhexidine solution and the effervescent agent.

Resistance of melanized yeast cells of Paracoccidioides brasiliensis to antimicrobial oxidants and inhibition of phagocytosis using carbohydrates and monoclonal antibody to CD18

Paracoccidioides brasiliensis, a thermal dimorphic fungal pathogen, produces a melanin-like pigment in vitro and in vivo. We investigated the involvement of carbohydrates and monoclonal antibody to CD18, on phagocytosis inhibition, involving macrophage receptors and the resistance of melanized fungal cells to chemically generated nitric oxide (NO), reactive oxygen species (ROS), hypochlorite and H2O2. Our results demonstrate that melanized yeast cells were more resistant than nonmelanized yeast cells to chemically generated NO, ROS, hypochlorite and H2O2, in vitro. Phagocytosis of melanized yeast cells was virtually abolished when mannan, N-acetyl glucosamine and anti-CD18 antibody were added together in this system. Intratracheal infection of BALB/c mice, with melanized yeast cells, resulted in higher lung colony forming units, when compared to nonmelanized yeast cells. Therefore, melanin is a virulence factor of P. brasiliensis.

Oxidative stress response to menadione and cumene hydroperoxide in the opportunistic fungal pathogen Candida glabrata

Candida glabrata is an opportunistic fungal pathogen that can cause severe invasive infections and can evade phagocytic cell clearance. We are interested in understanding the virulence of this fungal pathogen, in particular its oxidative stress response. Here we investigated C. glabrata, Saccharomyces cerevisiae and Candida albicans responses to two different oxidants: menadione and cumene hydroperoxide (CHP). In log-phase, in the presence of menadione, C. glabrata requires Cta1p (catalase), while in a stationary phase (SP), Cta1p is dispensable. In addition, C. glabrata is less resistant to menadione than C. albicans in SP. The S. cerevisiae laboratory reference strain is less resistant to menadione than C. glabrata and C. albicans; however S. cerevisiaeclinical isolates (CIs) are more resistant than the lab reference strain. Furthermore, S. cerevisiae CIs showed an increased catalase activity. Interestingly, in SP C. glabrata and S. cerevisiae are more resistant to CHP than C. albicans and Cta1p plays no apparent role in detoxifying this oxidant.

The effect of combined bleaching techniques on oral microbiota.

Aims : To evaluate the antimicrobial activity of 10% and 37% carbamide peroxide during dental bleaching in three different modes. Materials and Methods : This five-week double-blind randomized controlled trial included 32 volunteers assigned to four groups (n = 8). Each group received bleaching agents or placebo as an in-office and at-home treatment. The dental bleaching techniques were: In-office bleaching (37% carbamide peroxide: CP37); at-home bleaching (10% carbamide peroxide: CP10) and the association of both (CP37 and CP10). Saliva samples were collected right before (baseline), right after, 12 hours after, and seven days after the treatment. Counts of total microorganisms, Streptococci, and Mutans streptococci were carried out. Friedman test (α = 0.05) was used to compare the microorganism counts. Results : The number of the all oral microorganisms remained stable during all experiment. Conclusions : No bleaching agent (CP37, CP10 or the combination of both) was able to reduce the oral microorganisms tested.

Effect of hydrogen peroxide topical application on the enamel and composite resin surfaces and interface.

OBJECTIVES: The objective of the present study was to analyze the superficial roughness and the interface between enamel and composite resin restorations after dental bleaching procedure. MATERIALS AND METHODS: Black's class V cavities were made and restored with composite resin, and the whole set, enamel-restorative material, was treated with 35% hydrogen peroxide. Seven procedures of 30 min each were performed. A profilometric assessment was carried out before and after the treatment of each sample, and roughness scores were obtained. Treated and untreated samples were analyzed under scanning electronic microscope and images of their surface were obtained. RESULTS AND CONCLUSION: The treatment with 35% hydrogen peroxide caused no alteration in the interface between enamel and composite resin, Tetric Ceram, fillings and the topical application of 35% hydrogen peroxide on enamel and composite resin, Tetric Ceram, caused an alteration of their surface topography, featuring a predominance of depressions after the bleaching treatment.

Down syndrome critical region 1 enhances the proteolytic cleavage of calcineurin

Down syndrome critical region 1 (DSCR1), an oxidative stress-response gene, interacts with calcineurin and represses its phosphatase activity. Recently it was shown that hydrogen peroxide inactivates calcineurin by proteolytic cleavage. Based on these facts, we investigated whether oxidative stress affects DSCR1-mediated inactivation of calcineurin. We determined that overexpression of DSCR1 leads to increased proteolytic cleavage of calcineurin. Convertsely, knockdown of DSCR1 abolished calcineurin cleavage upon treatment with hydrogen peroxide. The PXIIXT motif in the COOH-terminus of DSCR1 is responsible for both binding and cleavage of calcineurin. The knockdown of overexpressed DSCR1 in DS fibroblast cells also abrogated calcineurin proteolysis by hydrogen peroxide. These results suggest that DSCR1 has the ability to inactivate calcineurin by inducing proteolytic cleavage of calcineurin upon oxidative stress.

Permeability of different groups of maxillary teeth after 38 percent hydrogen peroxide internal bleaching

This study evaluated the influence of internal tooth bleaching with 38 percent hydrogen peroxide (H2O2) on the permeability of the coronal dentin in maxillary anterior teeth and premolars. Seventy teeth (14 per group) were used: central incisors (CI), lateral incisor (LI), canines (C), first premolars (1PM) and second premolars (2PM). Pulp chamber access and transversal sectioning at 2 mm from the cementoenamel junction were performed and the specimens were divided into 2 groups (n= 7): a) no treatment and b) bleaching with 38 percent H2O2. The bleaching agent was applied to the buccal surface and to the pulp chamber for 10 min. This procedure was repeated 3 times. The specimens were processed histochemically with copper sulfate and rubeanic acid, sectioned longitudinally, and digitalized in a scanner. The area of stained dentin was measured using Image Tool software. Data were analyzed statistically by ANOVA and Tukey's HSD test (?=0.05). There was statistically significant difference (p<0.001) among the untreated groups, CI (0.23 ± 0.26) having the lowest permeability and LI (10.14 ± 1.89) the highest permeability. Among the bleached groups, dentin permeability was increased in all groups of teeth except for 2PM. It may be concluded that bleaching with 38 percent H2O2 affected dentin permeability near the pulp chamber in maxillary anterior teeth and in first and second premolars.

Este estudo avaliou a influência do clareamento interno com peróxido de hidrogênio (H2O2) a 38 por cento na permeabilidade da dentina coronária de dentes anteriores superiores e pré-molares superiores. Quatorze incisivos centrais (IC), incisivos laterais (IL), caninos (C), primeiros (1PM) e segundos (2PM) pré-molares foram seccionados transversalmente e distribuídos em 2 grupos (n=7) sendo: G1: não receberam tratamento e, G2: clareados com aplicação de gel na face vestibular e câmara pulpar por 10 min, repetido 3 vezes. Os espécimes foram processados histoquimicamente por meio de imersão em sulfato de cobre e ácido rubeânico e digitalizados em escaner. A área corada foi aferida (Programa Image Tool). Os dentes que não receberam tratamento, apresentaram diferença estatisticamente significante (p<0,001), sendo o ICS (0,23 ± 0,26) e o ILS (10,14 ± 1,89) os grupo com os menores e os maiores valores de permeabilidade, respectivamente. Quando clareados, a permeabilidade coronária dos grupos dentais foi aumentada, exceto no grupo do 2PM. Concluiu-se que a permeabilidade da dentina coronária nos dentes anteriores superiores e primeiros pré-molares foi alterada pelo clareamento dental interno.

Spectrophotometric assessment of the effects of 10 percent carbamide peroxide on enamel translucency

Tooth shade results from the interaction between enamel color, enamel translucency and dentine color. A change in any of these parameters will change a tooth’s color. The objective of this study was to evaluate the changes occurring in enamel translucency during a tooth whitening process. Fourteen human tooth enamel fragments, with a mean thickness of 0.96 mm (± 0.3 mm), were subjected to a bleaching agent (10 percent carbamide peroxide) 8 hours per day for 28 days. The enamel fragment translucency was measured by a computer controlled spectrophotometer before and after the bleaching agent applications in accordance with ANSI Z80.3-1986 - American National Standard for Ophthalmics - nonprescription sunglasses and fashion eyewear-requirements. The measurements were statistically compared by the Mann-Whitney non-parametric test. A decrease was observed in the translucency of all specimens and, consequently, there was a decrease in transmittance values for all samples. It was observed that the bleaching procedure significantly changes the enamel translucency, making it more opaque.

Free radical induced damages to rat liver subcellular organelles: inhibition by Andrographis paniculata extract.

Aqueous extract of Andrographis paniculata was examined for antioxidant activity using rat liver subcellular organelles as model systems. The study deals with two important biological oxidative agents, ascorbate-Fe(+2) and AAPH generating hydroxyl and peroxyl radical, respectively. Oxidative damage was examined against the inhibition of membrane peroxidation, protein oxidation and restoration in decreased SOD and catalase activity. The antimutagenic activity of Ap was examined following inhibition in AAPH induced strand breaks in plasmid pBR322 DNA. Extract was a potent scavenger of DPPH, ABTS radicals, exemplified by ESR signals, O2-*, *OH and H2O2, displayed excellent reducing power, FRAP potentials to reduce Fe (III) --> Fe (II) and had considerable amount of phenolics/ flavonoids contents, an effective antioxidant index. The observed antioxidant effect might be primarily due to its high scavenging ability for ROS. Effect was confirmed ex vivo following inhibition in peroxidation, restoration in SOD enzyme, SOD band intensity and protein degradation in Ap fed liver homogenate. Based on these results, it was concluded that the aqueous extract of Andrographis paniculata might emerge as a potent antiradical agent against various pathophysiological oxidants.

The role of super oxidized solution in the management of diabetic foot ulcer: our experience.

Dressing or preparation of the diabetic foot ulcer is very essential not only to reduce or prevent infection but also for the preparation for definite surgery, if necessary. Present article is about our experience in the evaluation of effectiveness of super oxidized solution in local treatment of diabetic foot ulcers. Out of 20 cases super oxidized solution helped in total healing in 8 cases, and prepared wounds for definite cover by reducing infection and promoting granulations which are pre requisites for definitive surgery in remaining 12 cases.

Effects of oxidizing and reducing agents on ovine pulmonary artery responses to nitric oxide donors, sodium nitroprusside and 3-morpholino-sydnonimine.

Nitrovasodilators-sodium nitroprusside (SNP; 10(-9)-10(-4) M) and 3-morpholino-sydnonimine (SIN-1; 10(-9)-10(-4) M) produced concentration-dependent relaxation of the fourth generation sheep pulmonary artery, preconstricted with 5-hydroxytryptamine (1 microM). Oxidizing agents [oxidized glutathione (GSSG, 1 mM) and CuSO4 (5 and 20 microM)] and reducing agents [dithiothreitol (DTT, 0.1 mM), ascorbic acid (1 mM) and reduced glutathione (GSH, 1 mM)] caused opposite effects on nitric oxide (NO)-induced vasodilation in the artery. Ascorbic acid and GSH potentiated the NO responses, while GSSG and CuSO4 inhibited relaxation caused by the nitrovasodilators. DTT, however, reduced the relaxant potency and efficacy of SNP and SIN-1. Pretreatment of the pulmonary artery strips with DTT (0.1 mM) inhibited SNP (10 microM)-induced Na(+)-K(+)-ATPase activity, while ascorbic acid (1 mM) and GSH (1 mM) had no effect either on basal or SNP (10 microM)-stimulated 86Rb uptake, an index of Na(+)-K(+)-ATPase activity, in ovine pulmonary artery. The results suggest that reducing agents like ascorbic acid may have beneficial effect in improving the vascular function under oxidative stress.

Protective effect of coenzyme Q10 in simvastatin and gemfibrozil induced rhabdomyolysis in rats.

Administration of simvastatin (80 mg/kg, po. evening dose) and gemfibrozil (600 mg/kg, po twice) for 30 days produced significant decrease in the level of reduced glutathione, superoxide dismutase, catalase and increase in the level of lipid peroxidation and various serum parameters (creatine phosphokinase, lactate dehydrogenase, serum glutamate oxaloacetate transaminase, creatinine, urea and blood urea nitrogen). This suggested involvement of oxidative stress in rhabdomyolysis. Increase in the level of reduced glutathione, superoxide dismutase, catalase and decrease in the level of lipid peroxidation and serum parameters after administration of antioxidant CoQ10 (10 mg/kg.ip) proved the protective effect of CoQ10 in rhabdomyolysis.