Skeletal Muscle Regeneration and Oxidative Stress Are Altered in Chronic Kidney Disease

Objective Skeletal muscle contusion is one of the most common muscle injury in sports medicine and traumatology. Bone marrow mesenchymal stem cells (BMSCs) transplantation is a promising strategy for muscle regeneration. However, the roles of BMSCs, especially the mechanisms involved, in the regeneration of contused skeletal muscle are still not fully recognized. The aim of the study is to evaluate the potential of BMSCs transplantation for muscle regeneration and mechanisms involved after contusion. Methods Ninety-nine C57BL/6J mice were divided into three groups: control group (n=11), muscle contusion and BMSCs treated group (n=44), muscle contusion and sham treated group (n=44). BMSCs were immediately transplanted into gastrocnemius muscles (GMs) following direct contusion. At different time points (3, 6, 12 and 24 days) post-injury, the animals were killed and then GMs were harvested. Morphological and gene expression analyses were used to elevate the effect of BMSCs transplantation and mechanisms involved. Results The results indicate that BMSCs transplantation impairs muscle regeneration, as well as more fibrotic scar formation after skeletal muscle contusion. Furthermore, macrophages, inflammatory cytokines, chemokines, matrix metalloproteinases and oxidative stress related enzymes were significantly increased after BMSCs transplantation. These results suggest that BMSCs transplantation impairs skeletal muscle regeneration and that macrophages, inflammatory cytokines, chemokines, matrix metalloproteinases and oxidative stress related enzymes may be involved in the process. Conclusions BMSCs transplantation aggravates inflammation, oxidative stress and fibrosis, and impairs skeletal muscle regeneration, which shed new light on the role of BMSCs in regenerative medicine and cautions the application of BMSCs for muscle injury.

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Macrophage Depletion Impairs Skeletal Muscle Regeneration: the Roles of Pro-fibrotic Factors, Inflammation, and Oxidative Stress

Inflammation ◽

10.1007/s10753-016-0438-8 ◽

2016 ◽

Vol 39 (6) ◽

pp. 2016-2028 ◽

Cited By ~ 26

Author(s):

Weihua Xiao ◽

Yu Liu ◽

Peijie Chen

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Muscle Regeneration ◽

Skeletal Muscle Regeneration ◽

Macrophage Depletion ◽

And Oxidative Stress

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Calycosin inhibited autophagy and oxidative stress in chronic kidney disease skeletal muscle atrophy by regulating AMPK/SKP2/CARM1 signalling pathway

Journal of Cellular and Molecular Medicine ◽

10.1111/jcmm.15514 ◽

2020 ◽

Vol 24 (19) ◽

pp. 11084-11099

Author(s):

Rong Hu ◽

Ming‐qing Wang ◽

Ling‐yu Liu ◽

Hai‐yan You ◽

Xiao‐hui Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Muscle Atrophy ◽

Signalling Pathway ◽

Skeletal Muscle Atrophy ◽

And Oxidative Stress

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Association of Sarcopenia and Gut Microbiota Composition in Older Patients with Advanced Chronic Kidney Disease, Investigation of the Interactions with Uremic Toxins, Inflammation and Oxidative Stress

Toxins ◽

10.3390/toxins13070472 ◽

2021 ◽

Vol 13 (7) ◽

pp. 472

Author(s):

Elisabetta Margiotta ◽

Lara Caldiroli ◽

Maria Luisa Callegari ◽

Francesco Miragoli ◽

Francesca Zanoni ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Gut Microbiota ◽

Inflammatory Cytokines ◽

Interleukin 10 ◽

Uremic Toxins ◽

Interleukin 12 ◽

European Working ◽

And Oxidative Stress

Background: Sarcopenia is a prevalent condition in chronic kidney disease (CKD). We determined gut microbiota (gMB) composition in CKD patients with or without sarcopenia. Furthermore, we investigated whether in these patients, there was any association between gMB, uremic toxins, inflammation and oxidative stress. Methods: We analyzed gMB composition, uremic toxins (indoxyl sulphate and p-cresyl sulphate), inflammatory cytokines (interleukin 10, tumor necrosis factor α, interleukin 6, interleukin 17, interleukin 12 p70, monocyte chemoattractant protein-1 and fetuin-A) and oxidative stress (malondialdehyde) of 64 elderly CKD patients (10 < eGFR < 45 mL/min/1.73 m2, not on dialysis) categorized as sarcopenic and not-sarcopenic. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 criteria. Results: Sarcopenic patients had a greater abundance of the Micrococcaceae and Verrucomicrobiaceae families and of Megasphaera, Rothia, Veillonella, Akkermansia and Coprobacillus genera. They had a lower abundance of the Gemellaceae and Veillonellaceae families and of Acidaminococcus and Gemella genera. GMB was associated with uremic toxins, inflammatory cytokines and MDA. However, uremic toxins, inflammatory cytokines and MDA were not different in sarcopenic compared with not-sarcopenic individuals, except for interleukin 10, which was higher in not-sarcopenic patients. Conclusions: In older CKD patients, gMB was different in sarcopenic than in not-sarcopenic ones. Several bacterial families and genera were associated with uremic toxins and inflammatory cytokines, although none of these latter substantially different in sarcopenic versus not-sarcopenic patients.

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SP436EFFECT OF LEVOCARNITINE ON LIPID METABOLISM AND OXIDATIVE STRESS IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfv193.44 ◽

2015 ◽

Vol 30 (suppl_3) ◽

pp. iii522-iii522

Author(s):

Mariana Koziy ◽

Liliya Martynyuk

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Lipid Metabolism ◽

Kidney Disease ◽

And Oxidative Stress

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Atractylenolide III Attenuates Muscle Wasting in Chronic Kidney Disease via the Oxidative Stress-Mediated PI3K/AKT/mTOR Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/1875471 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 1

Author(s):

Mingqing Wang ◽

Rong Hu ◽

Yanjing Wang ◽

Lingyu Liu ◽

Haiyan You ◽

...

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Skeletal Muscles ◽

Muscle Wasting ◽

Mtor Pathway ◽

C2c12 Myoblast ◽

Model Group ◽

Atractylenolide Iii

Oxidative stress contributes to muscle wasting in advanced chronic kidney disease (CKD) patients. Atractylenolide III (ATL-III), the major active constituent of Atractylodes rhizome, has been previously reported to function as an antioxidant. This study is aimed at investigating whether ATL-III has protective effects against CKD-induced muscle wasting by alleviating oxidative stress. The results showed that the levels of serum creatinine (SCr), blood urea nitrogen (BUN), and urinary protein significantly decreased in the ATL-III treatment group compared with the 5/6 nephrectomy (5/6 Nx) model group but were higher than those in the sham operation group. Skeletal muscle weight was increased, while inflammation was alleviated in the ATL-III administration group compared with the 5/6 Nx model group. ATL-III-treated rats also showed reduced dilation of the mitochondria, increased CAT, GSH-Px, and SOD activity, and decreased levels of MDA both in skeletal muscles and serum compared with 5/6 Nx model rats, suggesting that ATL-III alleviated mitochondrial damage and increased the activity of antioxidant enzymes, thus reducing the production of ROS. Furthermore, accumulated autophagosomes (APs) and autolysosomes (ALs) were reduced in the gastrocnemius (Gastroc) muscles of ATL-III-treated rats under transmission electron microscopy (TEM) together with the downregulation of LC3-II and upregulation of p62 according to Western blotting. This evidence indicated that ATL-III improved skeletal muscle atrophy and alleviated oxidative stress and autophagy in CKD rats. Furthermore, ATL-III could also increase the protein levels of p-PI3K, p-AKT, and p-mTOR in skeletal muscles in CKD rats. To further reveal the relevant mechanism, the oxidative stress-mediated PI3K/AKT/mTOR pathway was assessed, which showed that a reduced expression of p-PI3K, p-AKT, and p-mTOR in C2C12 myoblast atrophy induced by TNF-α could be upregulated by ATL-III; however, after the overexpression of Nox2 to increase ROS production, the attenuated effect was reversed. Our findings indicated that ATL-III is a potentially protective drug against muscle wasting via activation of the oxidative stress-mediated PI3K/AKT/mTOR pathway.

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