Chronic heart failure is the end stage of heart diseases caused by multiple causes. Myocardial cell injury is the key cause of cardiac function deterioration. Ferroptosis, an iron-dependent programmed death mode, is characterized by iron overload and excessive accumulation of lipid peroxides. Studies have demonstrated that inhibiting ferroptosis has a protective effect on myocardial cells. The theory of "harmful hyperactivity and responding inhibition" is an important rule developed by physicians to explain the generation and restriction of the five elements and the pathological imbalance of the human body, and can guide medication. Correlating with the nature, humans need to rely on the law of responding inhibition to maintain the harmony of five Zang-organs and the steady state of Fu-organs. The pathogenesis of ferroptosis in chronic heart failure highly coincides with the process of failing to "inhibition and hyperactivity becoming harmful". The initial factor of ferroptosis is the deficiency of heart Qi, which results in the inability to maintain the balance of cardiomyocyte redox system. The involvement of the five Zang-organs leads to the loss of distribution of body fluid and blood. As a result, the phlegm turbidity, blood stasis, and water retention in the meridians occur, which are manifested as the accumulation of iron and lipid peroxides, which is the aggravating factor of ferroptosis. The two factors interact with each other, leading to the spiral development and thus aggravating heart failure. According to the traditional Chinese medicine(TCM) pathogenesis of ferroptosis, the authors try to treat the chronic heart failure by stages in accordance with the general principle of restraining excess and alleviating hyperactivity. The early-stage treatment should "nourish heart Qi, regulate the five Zang-organs, so as to restrain excess". The middle-stage treatment should "active blood, resolve phlegm, dispel pathogen, and eliminate turbidity", so as to alleviate hyperactivity. The late-stage treatment should "warm Yang, replenish Qi, active blood, and excrete water". Following the characteristics of pathogenesis, the TCM intervention can reduce iron accumulation and promote the clearance of lipid peroxide, thus inhibiting ferroptosis and improving cardiac function.
Humans ; Ferroptosis ; Lipid Peroxides ; Medicine, Chinese Traditional ; Heart Failure/drug therapy* ; Chronic Disease ; Iron ; Water

Enhanced oxidative stress is a hallmark of cisplatin nephrotoxicity, and inhibition of poly(ADP-ribose) polymerase 1 (PARP1) attenuates oxidative stress during cisplatin nephrotoxicity; however, the precise mechanisms behind its action remain elusive. Here, using an in vitro model of cisplatin-induced injury to human kidney proximal tubular cells, we demonstrated that the protective effect of PARP1 inhibition on oxidative stress is associated with sirtuin 3 (SIRT3) activation. Exposure to 400 µM cisplatin for 8 hours in cells decreased activity and expression of manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase (GPX), and SIRT3, while it increased their lysine acetylation. However, treatment with 1 µM PJ34 hydrochloride, a potent PARP1 inhibitor, restored activity and/or expression in those antioxidant enzymes, decreased lysine acetylation of those enzymes, and improved SIRT3 expression and activity in the cisplatin-injured cells. Using transfection with SIRT3 double nickase plasmids, SIRT3-deficient cells given cisplatin did not show the ameliorable effect of PARP1 inhibition on lysine acetylation and activity of antioxidant enzymes, including MnSOD, catalase and GPX. Furthermore, SIRT3 deficiency in cisplatin-injured cells prevented PARP1 inhibition-induced increase in forkhead box O3a transcriptional activity, and upregulation of MnSOD and catalase. Finally, loss of SIRT3 in cisplatin-exposed cells removed the protective effect of PARP1 inhibition against oxidative stress, represented by the concentration of lipid hydroperoxide and 8-hydroxy-2'-deoxyguanosine; and necrotic cell death represented by a percentage of propidium iodide–positively stained cells. Taken together, these results indicate that PARP1 inhibition protects kidney proximal tubular cells against oxidative stress through SIRT3 activation during cisplatin nephrotoxicity.
Acetylation ; Catalase ; Cell Death ; Cisplatin* ; Deoxyribonuclease I ; Down-Regulation* ; Glutathione Peroxidase ; Humans ; In Vitro Techniques ; Kidney ; Lipid Peroxides ; Lysine ; Oxidative Stress* ; Plasmids ; Poly Adenosine Diphosphate Ribose* ; Poly(ADP-ribose) Polymerases* ; Propidium ; Sirtuin 3* ; Superoxide Dismutase ; Transfection ; Up-Regulation

OBJECTIVETo investigate the cytoprotective effects of Saeng-kankunbi-tang (, SKT), a herbal prescription consisting of Artemisia capillaris and Alisma canaliculatum, and its underlying mechanism involved.

METHODSIn mice, blood biochemistry and histopathology were assessed in carbon tetrachloride (CCl4)-induced oxidative hepatic injury in vivo. The animal groups included vehicle-treated control, CCl4, SKT 500 mg/(kg day) CCl4+SKT 200 or 500 mg/(kg day). In HepG2 cell, tert-butyl hydroperoxide (tBHP) induced severe oxidative stress and mitochondrial dysfunction in vitro. The cyto-protective effects of SKT were determined by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay, flfluorescence activated cell sorting analysis and western blotting.

RESULTSThe administration of SKT prevented liver damage induced by CCl4 in mice, by inhibition of hepatocyte degeneration and inflflammatory cell infifiltration as well as plasma parameters such as alanine aminotransferase (P<0.01). Moreover, treatment with tBHP induced hepatocyte death and cellular reactive oxygen species production in hepatocyte cell line. However, SKT pretreatment (30-300 μg/mL) reduced this cell death and oxidative stress (P<0.01). More importantly, SKT inhibited the ability of tBHP to induce changes in mitochondrial membrane transition in cell stained with rhodamine 123 P<0.01). Furthermore, treatment with SKT induced extracellular signal-regulated kinases-mediated nuclear factor erythroid-2-related factor 2 (Nrf2) activation as well as the expressions of heme oxygenase 1 and glutamate- cystein ligase catalytic, Nrf2 target genes.

CONCLUSIONSSKT has the ability to protect hepatocyte against oxidative stress and mitochondrial damage mediated by Nrf2 activation.

Animals ; Antioxidants ; pharmacology ; Carbon Tetrachloride ; Cell Death ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Hep G2 Cells ; Humans ; Liver ; drug effects ; enzymology ; pathology ; MAP Kinase Signaling System ; drug effects ; Mice, Inbred C57BL ; Mitochondria ; drug effects ; metabolism ; NF-E2-Related Factor 2 ; metabolism ; Oxidative Stress ; drug effects ; Peroxides ; Phosphorylation ; drug effects ; Protective Agents ; pharmacology ; Reactive Oxygen Species ; metabolism

Treatment with cisplatin for cancer therapy has a major side effect such as nephrotoxicity; however, the role of poly (ADP-ribose) polymerase 1 (PARP1) in necrosis in response to cisplatin nephrotoxicity remains to be defined. Here we report that cisplatin induces primary necrosis through PARP1 activation in kidney proximal tubular cells derived from human, pig and mouse. Treatment with high dose of cisplatin for 4 and 8 hours induced primary necrosis, as represented by the percentage of propidium iodide-positive cells and lactate dehydrogenase release. The primary necrosis was correlated with PARP1 activation during cisplatin injury. Treatment with PJ34, a potent PARP1 inhibitor, at 2 hours after injury attenuated primary necrosis after 8 hours of cisplatin injury as well as PARP1 activation. PARP1 inhibition also reduced the release of lactate dehydrogenase and high mobility group box protein 1 from kidney proximal tubular cells at 8 hours after cisplatin injury. Oxidative stress was increased by treatment with cisplatin for 8 hours as shown by 8-hydroxy-2'-deoxyguanosine and lipid hydroperoxide assays, but PARP1 inhibition at 2 hours after injury reduced the oxidative damage. These data demonstrate that cisplatin-induced PARP1 activation contributes to primary necrosis through oxidative stress in kidney proximal tubular cells, resulting in the induction of cisplatin nephrotoxicity and inflammation.
Animals ; Cisplatin* ; Humans ; Inflammation ; Kidney* ; L-Lactate Dehydrogenase ; Lipid Peroxides ; Mice ; Necrosis* ; Oxidative Stress ; Poly(ADP-ribose) Polymerases* ; Propidium

The effects of toluene in dimethylformamide (DMF)-induced hepatotoxicity were investigated with respect to the induction of cytochrome P-450 (CYP) and the activities of related enzymes. The rats were treated intraperitoneally with the organic solvents in olive oil (Single treatment groups: 450 [D1], 900 [D2], 1,800 [D3] mg DMF, and 346 mg toluene [T] per kg of body weight; Combined treatment groups: D1+T, D2+T, and D3+T) once a day for three days, while the control group received just the olive oil. Each group consisted of 4 rats. The activities of the xenobiotic metabolic enzymes and the hepatic morphology were assessed. The immunoblots indicated that the expression of CYP2E1 was considerably enhanced depending on the dosage of DMF and the CYP2E1 blot densities were significantly increased after treatment with both DMF and toluene, compared to treatment with DMF alone. The activities of glutathione-S-transferase and glutathione peroxidase were either decreased or remained unaltered after treatment with DMF and toluene, whereas the lipid peroxide levels were increased with increasing dosage of DMF and toluene. The liver tissue in the D3 group (1,800 mg/kg of DMF) showed signs of microvacuolation in the central vein region and a large necrotic zone around the central vein, in rats treated with both DMF (1,800 mg/kg) and toluene (D3T). These results suggest that the expression of CYP2E1 is induced by DMF and enhanced by toluene. These changes may have facilitated the accelerated formation of N-methylformamide (NMF) from toluene, and the generated NMF may directly induce liver damage.
Animals ; Body Weight ; Cytochrome P-450 CYP2E1 ; Cytochrome P-450 Enzyme System ; Dimethylformamide* ; Formamides ; Glutathione Peroxidase ; Lipid Peroxides ; Liver ; Olea ; Plant Oils ; Rats* ; Solvents ; Toluene* ; Veins ; Olive Oil

PURPOSE: To compare clinical outcomes of a 2.2 mm microcoaxial cataract surgery, using torsional mode and longitudinal mode. METHODS: In this comparative study, patients with bilateral cataract were assigned to get microcoaxial cataract surgery by torsional mode of infiniti in one eye and longitudinal mode of Stellaris(R) in the other eye. Primary outcome measures were US time (UST), cumulative dissipated energy (CDE), mean amount of balanced salt solution (BSS) used and surgical complications. Patients were seen 1, 7, 30, and 60 days after surgery. Postoperative outcome measures were the final best corrected visual acuity (BCVA), central corneal thickness (CCT), endothelial cell count and surgically induced astigmatism (SIA). RESULTS: The study evaluated 68 eyes of 34 patients (nuclear opalescence (NO)2: 40 eyes, and NO3: 28 eyes). CDE was significantly lower in torsional mode (3.52 +/- 2.93) than in longitudinal mode (6.20 +/- 3.32) (p = 0.001). Torsional mode (60.88 +/- 21.18 ml) had more BSS use than longitudinal mode (34.58 +/- 13.54 ml) (p < 0.001). There were no significant differences in postoperative BCVA, CCT change, endothelial change, and SIA (p > 0.05). CONCLUSIONS: The torsional mode may provide lower level of phacoemulsification energy than the longitudinal mode and Torsional mode is considered effective and safe phacoemulsification. However the surgical outcomes were not significantly different in 2.2 mm microcoaxial cataract surgery of moderate cataract. So surgeon can choose any phaco machine based on experience and preference.
Astigmatism ; Cataract ; Endothelial Cells ; Eye ; Humans ; Outcome Assessment (Health Care) ; Peroxides ; Phacoemulsification* ; Urea ; Visual Acuity

OBJECTIVETo evaluate the effects of a bleaching gel and a whitening strip on the microleakage of three different glass-ionomer cements.

METHODSForty-five freshly extracted human premolars were used and class V cavity was prepared on the buccal and lingual surfaces. The teeth were randomly assigned to A, B and C groups and restored as follows: Conventional strengthen glass-ionomer cement (Ketac Molar Easymix), compomer (F2000) and compomer (Dyract AP). Teeth were kept in distilled water at 37 degrees C for 7 days. Then the specimens were thermocycled for 500 times. Each group was randomly divided into 3 subgroups which were treated for 21 days with one of the following: Whitening strip (14% hydrogen peroxide), bleaching gel (10% carbamide peroxide), or distilled water (control). After bleaching, the teeth were placed in a solution of basic fuchsin dye for 24 hours, then the teeth were sectioned longitudinally to evaluate the dye penetration. The depth of staining along the tooth restoration interface was recorded with a stereomicroscope.

RESULTSThere were no signicant differences between the two bleaching agents in microleakage of restorations (P>0.05). The two bleaching agents did not significantly affect the microleakage of compomer (P>0.05), whereas the microleakage of glass-ionomer cement in the experimental groups was higher than that in the control group (P<0.05).

CONCLUSIONThere are no significant differences in microleakage of restorations between bleaching gel (10% carbamide peroxide) and whitening strip (14% hydrogen peroxide). The two bleaching agents do not significantly affect the microleakage of compomer but adversely affect the microleakage of strengthen glass-ionomer cement.

Bicuspid ; Bleaching Agents ; Compomers ; Composite Resins ; Dental Leakage ; Dental Restoration, Permanent ; Glass Ionomer Cements ; Humans ; Peroxides ; Urea ; analogs & derivatives

OBJECTIVES: To evaluate the accuracy of the Root ZX in teeth with simulated root perforation in the presence of gel or liquid type endodontic irrigants, such as saline, 5.25% sodium hypochlorite (NaOCl), 2% chlorhexidine liquid, 2% chlorhexidine gel, and RC-Prep, and also to determine the electrical conductivities of these endodontic irrigants. MATERIALS AND METHODS: A root perforation was simulated on twenty freshly extracted teeth by means of a small perforation made on the proximal surface of the root at 4 mm from the anatomic apex. Root ZX was used to locate root perforation and measure the electronic working lengths. The results obtained were compared with the actual working length (AWL) and the actual location of perforations (AP), allowing tolerances of 0.5 or 1.0 mm. Measurements within these limits were considered as acceptable. Chi-square test or the Fisher's exact test was used to evaluate significance. Electrical conductivities of each irrigant were also measured with an electrical conductivity tester. RESULTS: The accuracies of the Root ZX in perforated teeth were significantly different between liquid types (saline, NaOCl) and gel types (chlorhexidine gel, RC-Prep). The accuracies of electronic working lengths in perforated teeth were higher in gel types than in liquid types. The accuracy in locating root perforation was higher in liquid types than gel types. 5.25% NaOCl had the highest electrical conductivity, whereas 2% chlorhexidine gel and RC-Prep gel had the lowest electrical conductivities among the five irrigants. CONCLUSIONS: Different canal irrigants with different electrical conductivities may affect the accuracy of the Root ZX in perforated teeth.
Chlorhexidine ; Edetic Acid ; Electric Conductivity ; Electronics ; Electrons ; Peroxides ; Root Canal Irrigants ; Sodium Hypochlorite ; Tooth ; Urea ; Waxes

OBJECTIVETo investigate the effects of three differently concentrated at-home bleaching agents on the structure and the structure-related mechanical properties of human enamel.

METHODSSixty enamel specimens were randomly divided into four groups and treated with 10% carbamide peroxide (CP), 15% CP, 20% CP and distilled water, respectively. The bleaching process was 8 h/day for 14 consecutive days. Baseline and final atomic force microscopy (AFM) surface detection, Raman spectroscopy, attenuated total reflectance-infrared spectroscopy (ATR-IR), microhardness and fracture toughness (FT) measurements were carried out before and after bleaching experiments.

RESULTSCP didn't change the morphology of enamel. Meanwhile, the three bleached groups and the control group had no significant difference in root mean square detection (P = 0.774), ν(2)CO(3)(2-) : ν(1)ν(3)PO(4)(3-) (P = 0.263) and microhardness (P = 0.829). The percentage of relative Raman intensity in the three bleached groups and the control group were (105.74 ± 11.34)%, (104.46 ± 8.83)%, (99.52 ± 9.32)% and (97.62 ± 7.46)%, respectively. There was no significant difference among them (P = 0.062). However, the percentage of laser-induced fluorescence in the three bleached groups and the control group were (20.86 ± 7.23)%, (22.14 ± 7.34)%, (21.10 ± 7.59)% and (100.78 ± 3.70)%, respectively. There was significant difference between either of the bleached groups and the control group (P < 0.001). Moreover, FT declined significantly in the three groups (P = 0.024, P = 0.005, P = 0.013) when compared with the control group.

CONCLUSIONSUnder in vitro condition, three differently concentrated at-home bleaching agents wouldn't induce the demineralization and the decline of microhardness on enamel. However, the decrease of FT on enamel seemed to be inevitable after bleaching.

Dental Enamel ; drug effects ; Dose-Response Relationship, Drug ; Hardness ; drug effects ; Humans ; Microscopy, Atomic Force ; Peroxides ; administration & dosage ; pharmacology ; Random Allocation ; Spectrophotometry, Infrared ; Spectrum Analysis, Raman ; Surface Properties ; Tooth Bleaching ; Tooth Bleaching Agents ; administration & dosage ; pharmacology ; Tooth Demineralization ; chemically induced ; Urea ; administration & dosage ; analogs & derivatives ; pharmacology

Polyphenol-rich grape seeds have a beneficial effect on human health. The present study was performed to investigate the effects of grape seeds on antioxidant activities in rats. Male Sprague-Dawley rats were randomly divided into a control diet group (C), a high-fat diet group (HF), a 5% grape seed-supplemented control diet group (G), and a 5% grape seed-supplemented high-fat diet group (HG). Dietary supplementation with grape seeds reduced serum concentrations of lipid peroxides compared with those in the C and HF groups. The hepatic level of lipid peroxides decreased significantly in the grape seed groups compared with that in the C and HF groups. Superoxide dismutase activity in the G group increased significantly compared with that in the C group. Catalase activity tended to be higher by feeding grape seeds. The grape seed diet increased glutathione peroxidase activity in the C group. Glutathione-S-transferase activity increased significantly in the G group compared with that in the C group. Hepatic content of total glutathione increased significantly in the HG group but decreased significantly in the HF group. The ratio of reduced glutathione and oxidized glutathione increased by feeding the grape seed diet. Total vitamin A concentration was significantly higher in HG group than in other groups. Liver tocopherol content of the G and HG groups was significantly higher than that of the control groups. These results suggest that dietary supplementation with grape seeds is beneficial for suppressing lipid peroxidation in high fat-fed rats.
Animals ; Catalase ; Diet ; Diet, High-Fat ; Dietary Supplements ; Glutathione ; Glutathione Disulfide ; Glutathione Peroxidase ; Humans ; Lipid Peroxidation ; Lipid Peroxides ; Liver ; Male ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Seeds ; Superoxide Dismutase ; Tocopherols ; Vitamin A ; Vitis