Mechanism of captopril toxicity to a human mammary ductal carcinoma cell line in the presence of copper

Captopril (D3mercapto2methylpropanoylLproli ne) is an angiotensin converting enzyme (ACE) inhibitor, used widely in the treatment of hypertension and congestive heart failure. Captopril also inhibits proliferation of a variety of cell types, including several lacking ACE and renin acitvity. We have previously demonstrated that human mammary ductal carcinoma cells are among the cell types whose mitotic activity is inhibited by captopril. In those cells, captopril also reduces estrogen receptor (ER) and increases progesterone receptor (PR) concentrations. The present study evaluated the mechanism of captopril's antiproliferative action in an ER/PRnegative human mammary ductal carcinoma cell line, Hs578T. Cells grown in a 10% serum medium showed negligible changes in the presence of captopril alone. However, in the presence of subphysiologic concentrations of copper salts or copperloaded ceruloplasmin, captopril caused a dosedependent reduction in cell number, thymidine incorporation and mitochondrial dehydrogenase activity. In contrast, iron salts and ironsaturated transferrin had no effect on captopril activity. Catalase and horseradish peroxidase nullified the cytotoxic effects of captopril/Cu⁺⁺, whereas H₂O₂ mimicked those effects. These data are consistent with the notion of a coppercatalyzed oxidation of captopril, leading to the generation of H₂O₂ as the cytotoxin to this clinically important cell type.     

Streptozotocin induced activation of oxidative stress responsive splenic cell signaling pathways: Protective role of arjunolic acid

Present study investigates the beneficial role of arjunolic acid (AA) against the alteration in the cytokine levels and simultaneous activation of oxidative stress responsive signaling pathways in spleen under hyperglycemic condition. Diabetes was induced by injection of streptozotocin (STZ) (at a dose of 70 mg/kg body weight, injected in the tail vain). STZ administration elevated the levels of IL-2 as well as IFN-γ and attenuated the level of TNF-α in the sera of diabetic animals. In addition, hyperglycemia is also associated with the increased production of intracellular reactive intermediates resulting with the elevation in lipid peroxidation, protein carbonylation and reduction in intracellular antioxidant defense. Investigating the oxidative stress responsive cell signaling pathways, increased expressions (immunoreactive concentrations) of phosphorylated p65 as well as its inhibitor protein phospho IκBα and phosphorylated mitogen activated protein kinases (MAPKs) have been observed in diabetic spleen tissue. Studies on isolated splenocytes revealed that hyperglycemia caused disruption of mitochondrial membrane potential, elevation in the concentration of cytosolic cytochrome c as well as activation of caspase 3 leading to apoptotic cell death. Histological examination revealed that diabetic induction depleted the white pulp scoring which is in agreement with the reduced immunological response. Treatment with AA prevented the hyperglycemia and its associated pathogenesis in spleen tissue. Results suggest that AA might act as an anti-diabetic and immunomodulatory agent against hyperglycemia.     

四大怀药延缓衰老作用的研究

本实验观察了怀牛膝、怀菊花、怀山药、怀地黄各单味药及四药合剂对小鼠血中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)活性和过氧化脂质(LPO)的影响。结果表明,"四大怀药"合剂可明显增强鼠血中 SOD 的活性和 GSH-PX 的活力,使 LPO 显著降低。各单味药亦可增强 GSH-Px 的活性,使 LPO 降低。上述结果说明,四大怀药可能具有延缓衰老的作用。     

超氧化物歧化酶及过氧化氢酶对辐射所致红细胞溶血及脂类过氧化的影响

辐射所致红细胞溶血率不仅随照射剂量增加而增加,而且随放置时间的延长,溶血率也相应增加。加入牛红细胞超氧化物歧化酶或从牛肝中纯化的过氧化氢酶可使溶血率显著减少。辐射可使红细胞发生脂类过氧化,其脂类过氧化值随着照射剂量增加而增加。加入超氧化物歧化酶,对脂类过氧化的减轻作用不明显或很轻微,但加入过氧化氢酶却有较强的减轻脂类过氧化的效果,而且还观察到茜甙减轻脂类过氧化的效能类似维生素E。     

The use of sodium thiosulfate for inactivating residual hydrogen peroxide on contact lenses after disinfection

Due to the number of soft contact lens wearers who cannot tolerate the ocular irritating side effects of conventional chemical disinfecting systems, there has been a noticeable shift towards the use of safer hydrogen peroxide systems for disinfecting contact lenses Two major hydrogen peroxide systems are currently available in the market place. One uses platinum discs for neutralizing residual hydrogen peroxide on contact lenses, while the other uses the entyme catalase. However, these neutralizing systems, effective as they may seem, are relatively unstable This artick shows that a new hydrogen peroxide neutralizing solution containing sodhm thiosulfate, is a viable alternative to platinum or catalase. Its natural biochemical bases, stability, safety and efficacy, make sodium thiosulfate a desirable chemical for neutralizing residual hydrogen peroxide     

A double‐blind,randomized trial of 0.05% betamethasone vs. topical catalase/dismutase superoxide in vitiligo

Background Among all the topical immunomodulators, vitiligo's mainstay therapy includes topical corticosteroids. Many other non‐immune theories have also been suggested for vitiligo's pathogenesis, but the role of oxidative stress has gained more importance in recent years. Objective To compare the effect of topical 0.05% betamethasone vs. catalase/dismutase superoxide (C/DSO). Study design Randomized, matched‐paired, double‐blind trial. Setting Dermatology Section, University of Antioquia, Medellín, Colombia. Subjects Patients (aged > 18 years or between 12 and 18 years) with parent's informed consent, with stable or active bilateral vitiligo. Intervention Topical 0.05% betamethasone or C/DSO. Methods Two lesions similar to each other in size were chosen. All assessments were made by two blinded investigators, and photographs were subjected to morphometry analysis. Main outcome Skin repigmentation by digital morphometry. Results Twenty‐five patients were enrolled in the study (21 women and 4 men). Mean age of participants was 40 years (range: 12–74 years). One patient on C/DSO experienced a mild local erythematous papular rash that self‐resolved. At 4 months of therapy, there was no statistical difference on the percentage of repigmentation between betamethasone and C/DSO (5.63% ± 27.9 vs. 3.22% ± 25.8, respectively, P = 0.758). After 10 months of therapy, the percentage of skin repigmentation increased to 18.5 ± 93.14% with betamethasone and to 12.4 ± 59% with C/DSO, but again, we found no statistical differences (P = 0.79). Discussion and conclusions Few studies have described objective methods to evaluate repigmentation among vitiligo patients. Digital morphometry provides an objective assessment of repigmentation in vitiligo. Objective vitiligo repigmentation with topical C/DSO at 10 months is similar to topical 0.05% betamethasone. Although a mild adverse effect was related to the use of C/DSO, such finding was not severe enough to discontinue treatment.     

Effects of Schisanhenol on Respiratory Burst in Rat Neutrophils

Schisanhenol(Sal),anactivecomponentisolatedfrailSchizandraerubriflora,hasbeendemonstratedtohaveprotectiveeffectagainstCCI',galactosamineandacetaminopheninducedliverinjuryandsuggestedasananti--oxid..t(1'2).Histologicalinvestigationsshowedthattherewereinfiltrationofpolymorphonuclearcellsandmacrophagesintheinjuredliverinducedbygalactosamine(').Schlay,etal(4)discoveredthatbothneutrophildegenerationandlivercellleakageinthegalactosamineinducedliverinjurycanbeprotectedbyturpentinepretreatment,sugge…     

Activity of Superoxide Dismutase and Catalase in Fenugreek (Trigonella foenum-graecum) in Response to Carbendazim

Fenugreek (Trigonella foenum-graecum) is an annual herb, used as a spice and traditionally as medicine. Fenugreek finds its uses in treating hyperglycemia, hyperlipidemia and disorders of gastro-intestinal and cardiovascular systems. Fenugreek cultivation in India is affected by fungal diseases like root-rot and damping-off and fungicides like carbendazim are used to overcome these infections. Fungicides play both positive and negative role in plants; fungicides protect plants from diseases and also exert oxidative stress simultaneously. This report is on the response of antioxidants, superoxide dismutase and catalase in fenugreek seeds and plants treated to different concentrations of carbendazim.     

Effects of short-term capsaicin treatment on formalin and nitrogen dioxide induced changes in lipid peroxidation and antioxidant enzyme system in rat lung

Exposure of rats to formalin and nitrogen dioxide vapour caused a significant increase in values of the lung wet wt/dry wt ratio (oedema formation) and lipid peroxidation. These effects were not observed in rats treated with short-term capsaicin, either before or after exposure to the two gases. This protective action of short-term capsaicin treatment can possibly be linked with the strengthening of the pulmonary antioxidant enzyme defence system by capsaicin.