Redox Report最新文献

Background: The study was undertaken to evaluate the effect of 6-week supplementation with a daily dose of 2g of curcumin on VO_2max and prooxidant/antioxidant homeostasis in middle-aged amateur long-distance runners during the preparatory period of the macrocycle.

Methods: Thirty runners were randomly assigned to a placebo group (PL) and a curcumin-supplemented group (CU). Their VO_2max was assessed before supplementation and after 6 weeks of supplementation. Venous blood samples were collected from the participants at rest, immediately after exercise, and after 1h of recovery to evaluate the activity of antioxidant enzymes (SOD, CAT, GPx), non-enzymatic antioxidants (GSH, UA) and sirtuin 3 level (SIRT 3), as well as the levels of oxidative stress markers (TOS/TOC, MDA, and 8-OHdG) and muscle damage markers (CK, LDH, and Mb).

Results: VO_2max, the activity of enzymatic antioxidants, the concentrations of non-enzymatic antioxidants, the levels of oxidative stress markers, and the levels of muscle damage markers did not change significantly in the CU group over 6 weeks of supplementation with curcumin. However, the resting concentration of SIRT 3 was found to be significantly higher (p ≤ 0.05) compared with pre-supplementation.

Conclusion: Curcumin supplementation does not have a significant effect on VO_2max and prooxidant/antioxidant homeostasis in runners.

Background: Oxidative damage is critical in the pathogenesis of ovarian ischaemia/reperfusion (I/R) injury, and statins have been reported to exert antioxidant activity. However, the role of VCAM-1 and xanthine oxidase (XO)/uric acid (UA) in ovarian I/R injury is not known. Also, whether or not atorvastatin exerts antioxidant activity like other statins is unclear.

Objectives: This study investigated the involvement of VCAM-1 and XO/UA in ovarian I/R injury and the likely protective role of atorvastatin.

Methods: Forty female Wistar rats were randomized into sham-operated, ischaemia, ischaemia/reperfusion (I/R), ischaemia and atorvastatin, and I/R and atorvastatin.

Results: In comparison with the sham-operated group, atorvastatin blunted ischaemia and I/R-induced distortion of ovarian histoarchitecture and follicular degeneration. Also, atorvastatin alleviated ischaemia and I/R-induced rise in XO, UA, and malondialdehyde, which was accompanied by inhibition of ischaemia and I/R-induced reductions in reduced glutathione level, enzymatic antioxidant activities and increase in myeloperoxidase activity and TNF-α and IL-6 levels by atorvastatin treatment. Additionally, atorvastatin blocked ischaemia and I/R-induced increase in VCAM-1 expression, caspase 3 activity, 8-hydroxydeoxyguanosine level and ovarian DNA fragmentation index.

Conclusion: For the first time, this study revealed that atorvastatin-mediated downregulation of VCAM-1 and XO/UA/caspase 3 signaling averts oxidative injury, inflammation, and apoptosis induced by ovarian ischaemia/reperfusion injury.

Background: The number of neutrophils is significantly reduced in myelodysplastic syndrome (MDS), but the molecular basis remains unclear. We recently found that miR-34a was significantly increased in MDS neutrophils. Therefore, this study aims to clarify the effects of aberrant miR-34a expression on neutrophil counts.

Methods: miR-34a mimics/inhibitor transfection were performed in neutrophil-like differentiated HL60 (dHL60) cells, and a FACSCalibur flow cytometer was used to measure ROS production and apoptosis. In addition, the Cdc42-WASP-Arp2/3 pathway inhibitor (ML141) and activator (CN02) treated the dHL60 cells, and then ROS production, apoptosis and related proteins expression were detected. And, luciferase reporter assay to verify the relationship of miR-34a and the Cdc42-WASP-Arp2/3 pathway.

Results: overexpression of miR-34a could induce ROS production and apoptosis, decrease the expression levels of DOCK8, p-WASP, WASP, Arp2, Arp3, and increase F-actin's expression. Meanwhile, knockdown of miR-34a could decrease ROS production and apoptosis, increase the expression of DOCK8, p-WASP, WASP, Arp2, Arp3, and decrease F-actin's expression. Immunofluorescence staining showed aberrant miR-34a and Cdc42-WASP-Arp2/3 pathway could induce F-actin membrane transfer. Luciferase reporter assay indicated that DOCK8 was a direct target gene of miR-34a.

Conclusion: These data indicates miR-34a may induce neutrophil apoptosis by regulating Cdc42-WASP-Arp2/3 pathway-mediated F-actin remodeling and ROS production.

Objective: To investigate the renoprotective, the antioxidant, and the anti-inflammatory impact of a combination of SPL and ZnO-NPs to combat against chronic kidney disease (CKD).

Methods: In total, 50 males of rats were distributed into 5 groups (10 rats each); normal group, adenine sulfate (0.25% in diet for 10 days) (CKD) group. After the last dose of adenine sulfate, rats were divided into three groups: SPL + Adenine sulfate group; rats were treated orally by mixing SPL (20 mg/kg/day) into chow for 8 weeks, ZnO-NPs + Adenine sulfate group; rats were injected intraperitoneally with ZnO-NPs (5 mg/kg) three times weekly for 8 weeks, ZnO-NPs + SPL + Adenine sulfate group; rats were injected with the same previous doses for 8 weeks.

Results: Each of SPL and ZnO-NPs up-regulated antioxidant genes (Nrf2 and HO-1), down-regulated fibrotic and inflammatory genes (TGF-β1, Wnt7a, β-catenin, fibronectin, collagen IV, α-SMA, TNF-α, and IL-6) compared to CKD. Furthermore, a combination of SPL and ZnO-NPs resulted in a greater improvement in the measured parameters than a single treatment.

Conclusion: The therapeutic role of SPL was enhanced by the antioxidant and the anti-inflammatory role of ZnO-NPs, which presented a great renoprotective effect against CKD.

Objective: The inhibiting effect of Norcantharidin (NCTD) on IL-6 (interleukin-6) and STAT3 and the involvement of the IL-6/STAT3 pathway in hepcidin expression prompted us to speculate that NCTD could affect iron metabolism.

We examined the effects of NCTD on serum iron (SI) and transferrin (Tf) saturation, iron and ferritin light chain (FTL), transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), ferroportin 1 (Fpn1), iron regulatory protein 1 (IRP1) and hepcidin, as well as IL-6 and STAT3 in the liver, spleen and duodenum of mice treated with lipopolysaccharide (LPS) in vivo, using RT-PCR, Western blotting and immunofluorescence analysis.

NCTD could increase SI and Tf saturation and reduce tissue iron and FTL content by affecting expression of cell-iron transport proteins TfR1, DMT1 and Fpn1. The impact of NCTD on TfR1, DMT1 and Fpn1 expression is mediated by up-regulating IRP1 and down-regulating hepcidin expression, while NCTD-induced down-regulation of hepcidin is mediated by the IL-6/STAT3 signalling pathway in LPS-treated mice.

NCTD affects iron metabolism by modifying the expression of IL-6/JAK2/STAT3/hepcidin and IRP1 and suggest that the ability of NCTD to reduce tissue iron contents may be a novel mechanism associated with the anti-cancer effects of NCTD.

Objectives: Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes mellitus. Oxidative stress resulting from high glucose promotes accumulation of ECM and development of DN. Activation of Nrf2 could attenuate oxidative stress and following accumulation of ECM. To find novel therapy for DN, we explored the effects of swinhoeic acid from Potentilla fragarioides on mesangial cells under high glucose and underlying mechanisms.

Methods: CCK-8 and BrdU incorporation assays for survival of mesangial cells gave the concentration of swinhoeic acid in following investigations. ROS, MDA, SOD and CAT were determined. And ECM proteins and their upstream regulators TGF-β₁ and CTGF were detected using ELISA assays. Activation of Nrf2 was explored by immunofluorescence staining together with luciferase reporter assay. To demonstrate the role of Nrf2 activation, siRNA interference was performed. And co-immunoprecipitation assay was used to elucidate swinhoeic acid affects the interaction between Keap1 and Nrf2.

Results: Swinhoeic acid at 10 and 20 μM attenuated oxidative stress and accumulation of ECM in mesangial cells under high glucose. Itactivated Nrf2 in a Keap1-dependent manner, which was involved in its effects.

Conclusion: Swinhoeic acid ameliorates oxidative stress and accumulation of ECM resulting from high glucose in mesangial cells via activating Nrf2 in Keap1-dependent manner.

Objectives: Sevoflurane is identified as an effective candidate drug for acute lung injury (ALI) treatment, but its curing effects and detailed mechanisms have not been fully disclosed. The present study was designed to resolve this academic issue.

Methods: The ALI mice models were established, and Hematoxylin-eosin staining assay was performed to examine tissue morphologies. Cell viability was determined by CCK-8 assay, and Annexin V-FITC/PI double staining assay was used to examine cell apoptosis. The expression levels of proteins were determined by performing Western Blot analysis and immunofluorescence staining assay. ROS levels were examined by using DCFH-DA staining assay.

Results: In this study, we investigated this issue and the ALI models were respectively established by treating the BALB/c mice and the murine macrophage cell line RAW264.7 with different concentrations of lipopolysaccharide (LPS) in vivo and in vitro, which were subsequently subjected to sevoflurane co-treatment. The results showed that sevoflurane reduced LPS-induced ALI in mice and suppressed LPS-triggered oxidative stress and apoptotic cell death in the RAW264.7 cells. Interestingly, we evidenced that the elimination of reactive oxygen species (ROS) by N-acetyl-L-cysteine (NAC) reversed LPS-induced cell apoptosis in RAW264.7 cells. Then, we verified that sevoflurane suppressed oxidative damages to restrain LPS-induced apoptotic cell death in the RAW264.7 cells through activating the anti-oxidant Keap1/Nrf2 pathway. Mechanistically, sevoflurane down-regulated Keap1 and upregulated Nrf2 in nucleus to activate the downstream anti-oxidant signaling cascades, which further ameliorated LPS-induced cell apoptosis and lung injury by eliminating oxidative damages.

Discussion: Taken together, our study illustrated that the sevoflurane attenuates LPS-induced ALI by inhibiting oxidative stress-mediated apoptotic cell death and inflammation, and the Keap1/Nrf2 pathway played an important role in this process.

Objectives: Necroptosis is a tightly adjusted inflammatory necrotizing cell death signaling pathway that participates in pathogenesis of discrete diseases as rheumatoid arthritis (RA). Irisin is a myokine with immuno-modulatory effect. Evaluation of irisin efficiency as a novel therapeutic agent in experimentally induced RA via modulating immuno-inflammatory, necroptotic molecular and biochemical signaling pathways.

Methods: RA was induced in 30 female Wister albino rats by a single subcutaneous injection of collagen-II with incomplete Freund's adjuvant (CII-IFA) followed by booster immunization dose 10 days later. After 14 days of the injection, arthritis chronic phase was precipitated. 15 rats were treated by S.C irisin injection daily for 4 weeks. Joint tissue homogenate RIPK-3, MLKL, HMGB1, MCP1, IL-6, CHIT1, MDA, and PN levels were assessed calorimetrically. However, TNF-α mRNA expression level was evaluated by the qrt-PCR technique.

Results: The results showed that irisin significantly decreases the level of all assessed biochemical parameters, except MDA, which was significantly increased in comparison with the correspondent values in the arthritic group with no treatment (ttt).

Conclusions: Irisin exhibits therapeutic anti-inflammatory and antioxidant effects via modulating immuno-inflammatory, necroptotic molecular, and biochemical signaling pathways in experimentally induced RA in rats.

Abbreviations: RA: rheumatoid arthritis; RIPK3: receptor-interacting protein kinase 1; MLKL: mixed lineage kinase domain-like protein; HMGB1: High-mobility group protein box 1; MCP1: Monocyte chemoattractant protein 1; IL-6: Interleukin 6; CHIT1: Chitotriosidase; MDA: Malondialdehyde; PN: Peroxynitrite; TNF-α: Tumor Necrosis Factor; qrt-PCR: quantitative real-time reverse transcription PCR; CII-IFA: collagen-II with incomplete Freund's adjuvant; ttt: treatmentNote: TNF-α gene (NCBI GenBank Nucleotide accession # NM_012675.3); The housekeeping gene GAPDH (NCBI GenBank Nucleotide accession # NM_017008.4).

Background: Inflammation and oxidative stress (OS) are important contributors to psoriasis pathogenesis. Proanthocyanidins (PCs) have anti-inflammatory and anti-oxidative activities. Previously, we discovered that PCs alleviated psoriasis-like mice symptoms, likely via mitigating inflammation and OS damage.

Objective: To elucidate the protective mechanism underlying PCs against the damage of TNF-ɑ-induced psoriasis-like cell models.

Methods: Psoriasis-like cell models were established with 7.5 ng/mL TNF-ɑ and then subjected to different-concentrations PCs treatment. Finally, inflammatory and oxidative parameters were determined. Besides, LY294002 (PI3K inhibitor) and ZnPP (HO-1 inhibitor) were employed to investigate the roles of PI3K/AKT and HO-1 in PCs against psoriasis-like cell models.

Results: After TNF-α treatment, cells organized tightly and proliferated greatly (P<0.01); HO-1 expression dropped obviously, along with the increased OS/inflammatory indicators and the decreased antioxidants (P<0.05); consequently, psoriasis-like cell models were well established. In the presence of PCs, nevertheless, the proliferation rate and number of psoriasis-like cells evidently decreased (P<0.01), accompanied with enhanced HO-1 and antioxidants, and lowered OS/inflammatory indicators as well as phosphorylated JAK2/STAT3/PI3/AKT (P<0.01). Similar changes appeared after LY294002 pretreatment, regardless of PCs or not. But after ZnPP pretreatment with or without PCs, the opposite occurred.

Conclusion: The study reveals that PCs can suppress psoriasis-like cell proliferation and reduce inflammatory/OS damage through PI3K/AKT inhibition and HO-1 activation, thus promising a candidate for PCs in treating psoriasis.