Effects of dietary glucose oxidase, catalase, or both supplementation on reproductive performance, oxidative stress, fecal microflora and apoptosis in multiparous sows

AbstractThe management of diabetic ulcer (DU) to rescue stalled wound healing remains a paramount clinical challenge due to the spatially and temporally coupled pathological wound microenvironment that features hyperglycemia, biofilm infection, hypoxia and excessive oxidative stress. Here we present a pH-switchable nanozyme cascade catalysis (PNCC) strategy for spatial–temporal modulation of pathological wound microenvironment to rescue stalled healing in DU. The PNCC is demonstrated by employing the nanozyme of clinically approved iron oxide nanoparticles coated with a shell of glucose oxidase (Fe3O4-GOx). The Fe3O4-GOx possesses intrinsic glucose oxidase (GOx), catalase (CAT) and peroxidase (POD)-like activities, and can catalyze pH-switchable glucose-initiated GOx/POD and GOx/CAT cascade reaction in acidic and neutral environment, respectively. Specifically, the GOx/POD cascade reaction generating consecutive fluxes of toxic hydroxyl radical spatially targets the acidic biofilm (pH ~ 5.5), and eradicates biofilm to shorten the inflammatory phase and initiate normal wound healing processes. Furthermore, the GOx/CAT cascade reaction producing consecutive fluxes of oxygen spatially targets the neutral wound tissue, and accelerates the proliferation and remodeling phases of wound healing by addressing the issues of hyperglycemia, hypoxia, and excessive oxidative stress. The shortened inflammatory phase temporally coupled with accelerated proliferation and remodeling phases significantly speed up the normal orchestrated wound-healing cascades. Remarkably, this Fe3O4-GOx-instructed spatial–temporal remodeling of DU microenvironment enables complete re-epithelialization of biofilm-infected wound in diabetic mice within 15 days while minimizing toxicity to normal tissues, exerting great transformation potential in clinical DU management. The proposed PNCC concept offers a new perspective for complex pathological microenvironment remodeling, and may provide a powerful modality for the treatment of microenvironment-associated diseases. Graphical Abstract

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N-acetylcysteine prevents glucose/glucose oxidase-induced oxidative stress, mitochondrial damage and apoptosis in H9c2 cells

Life Sciences ◽

10.1016/j.lfs.2008.12.016 ◽

2009 ◽

Vol 84 (11-12) ◽

pp. 328-336 ◽

Cited By ~ 64

Author(s):

Santosh Kumar ◽

Sandhya L. Sitasawad

Keyword(s):

Oxidative Stress ◽

Glucose Oxidase ◽

Mitochondrial Damage ◽

H9c2 Cells

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Mechanism for antioxidative effects of thiazolidinediones in pancreatic β-cells

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00120.2011 ◽

2011 ◽

Vol 301 (5) ◽

pp. E912-E921 ◽

Cited By ~ 13

Author(s):

Sung Soo Chung ◽

Min Kim ◽

Ji Seon Lee ◽

Byung Yong Ahn ◽

Hye Seung Jung ◽

...

Keyword(s):

Oxidative Stress ◽

Glucose Oxidase ◽

Antioxidant Effect ◽

Peroxisome Proliferator ◽

Β Cells ◽

Pancreatic Β Cells ◽

Antioxidative Effect ◽

Peroxisome Proliferator Activated Receptor ◽

Antioxidant Genes ◽

Glucose Stimulated Insulin Secretion

Thiazolidinediones (TZDs) are synthetic ligands of peroxisome proliferator-activated receptor-γ (PPARγ), a member of the nuclear receptor superfamily. TZDs are known to increase insulin sensitivity and also to have an antioxidative effect. In this study, we tested whether TZDs protect pancreatic β-cells from oxidative stress, and we investigated the mechanism involved in this process. To generate oxidative stress in pancreatic β-cells (INS-1 and βTC3) or isolated islets, glucose oxidase was added to the media. The extracellular and intracellular reactive oxygen species (ROS) were measured to directly determine the antioxidant effect of TZDs. The phosphorylation of JNK/MAPK after oxidative stress was detected by Western blot analysis, and glucose-stimulated insulin secretion and cell viability were also measured. TZDs significantly reduced the ROS levels that were increased by glucose oxidase, and they effectively prevented β-cell dysfunction. The antioxidative effect of TZDs was abolished in the presence of a PPARγ antagonist, GW9662. Real-time PCR was used to investigate the expression levels of antioxidant genes. The expression of catalase, an antioxidant enzyme, was increased by TZDs in pancreatic β-cells, and the knockdown of catalase significantly inhibited the antioxidant effect of TZDs. These results suggest that TZDs effectively protect pancreatic β-cells from oxidative stress, and this effect is dependent largely on PPARγ. In addition, the expression of catalase is increased by TZDs, and catalase, at least in part, mediates the antioxidant effect of TZDs in pancreatic β-cells.

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