N‐Acetyl Cysteine Treatment Restores Early Phase Fracture Healing in Ethanol‐Fed Rats

Duryee, Michael J.; Dusad, Anand; Hunter, Carlos D.; Kharbanda, Kusum K.; Bruenjes, Joseph D.; Easterling, Karen C.; Siebler, Justin; Thiele, Geoffrey M.; Chakkalakal, Dennis A.

doi:10.1111/acer.13765

Cited by 9 publications

(9 citation statements)

References 41 publications

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“…After this analysis, 223 articles were potentially eligible for the review; however, 17 were excluded owing to missing data. Therefore, 206 files [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , …”

Section: Resultsmentioning

confidence: 99%

The Role of Oxidative Stress in Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies

Rabelo,

Andrade,

Costa

2024

Nutrients

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Alcoholic Fatty Liver Disease (AFLD) is characterized by the accumulation of lipids in liver cells owing to the metabolism of ethanol. This process leads to a decrease in the NAD+/NADH ratio and the generation of reactive oxygen species. A systematic review and meta-analysis were conducted to investigate the role of oxidative stress in AFLD. A total of 201 eligible manuscripts were included, which revealed that animals with AFLD exhibited elevated expression of CYP2E1, decreased enzymatic activity of antioxidant enzymes, and reduced levels of the transcription factor Nrf2, which plays a pivotal role in the synthesis of antioxidant enzymes. Furthermore, animals with AFLD exhibited increased levels of lipid peroxidation markers and carbonylated proteins, collectively contributing to a weakened antioxidant defense and increased oxidative damage. The liver damage in AFLD was supported by significantly higher activity of alanine and aspartate aminotransferase enzymes. Moreover, animals with AFLD had increased levels of triacylglycerol in the serum and liver, likely due to reduced fatty acid metabolism caused by decreased PPAR-α expression, which is responsible for fatty acid oxidation, and increased expression of SREBP-1c, which is involved in fatty acid synthesis. With regard to inflammation, animals with AFLD exhibited elevated levels of pro-inflammatory cytokines, including TNF-a, IL-1β, and IL-6. The heightened oxidative stress, along with inflammation, led to an upregulation of cell death markers, such as caspase-3, and an increased Bax/Bcl-2 ratio. Overall, the findings of the review and meta-analysis indicate that ethanol metabolism reduces important markers of antioxidant defense while increasing inflammatory and apoptotic markers, thereby contributing to the development of AFLD.

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Section: Resultsmentioning

confidence: 99%

The Role of Oxidative Stress in Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies

Rabelo,

Andrade,

Costa

2024

Nutrients

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“…By administering NAC, they found that ROS levels were suppressed to levels that allowed FOXO levels to decrease, restoring quality of endochondral ossification (Roper et al, 2016). Duryee et al had similar findings, showing that NAC decreased ROS in alcohol-fed mice and restored the normal innate immune response to fracture healing (Duryee et al, 2018). Taken together, NAC has profound antioxidant actions intracellularly and relatively low actions extracellularly, which make it a promising molecule to suppress ROS levels in osteoprogenitors while not significantly effecting the physiologic levels of ROS in the fracture environment.…”

Section: N-acetyl Cysteinementioning

confidence: 85%

Understanding Reactive Oxygen Species in Bone Regeneration: A Glance at Potential Therapeutics and Bioengineering Applications

Sheppard

Barfield

Barton

et al. 2022

Front. Bioeng. Biotechnol.

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Although the complex mechanism by which skeletal tissue heals has been well described, the role of reactive oxygen species (ROS) in skeletal tissue regeneration is less understood. It has been widely recognized that a high level of ROS is cytotoxic and inhibits normal cellular processes. However, with more recent discoveries, it is evident that ROS also play an important, positive role in skeletal tissue repair, specifically fracture healing. Thus, dampening ROS levels can potentially inhibit normal healing. On the same note, pathologically high levels of ROS cause a sharp decline in osteogenesis and promote nonunion in fracture repair. This delicate balance complicates the efforts of therapeutic and engineering approaches that aim to modulate ROS for improved tissue healing. The physiologic role of ROS is dependent on a multitude of factors, and it is important for future efforts to consider these complexities. This review first discusses how ROS influences vital signaling pathways involved in the fracture healing response, including how they affect angiogenesis and osteogenic differentiation. The latter half glances at the current approaches to control ROS for improved skeletal tissue healing, including medicinal approaches, cellular engineering, and enhanced tissue scaffolds. This review aims to provide a nuanced view of the effects of ROS on bone fracture healing which will inspire novel techniques to optimize the redox environment for skeletal tissue regeneration.

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“…A previous report showed that Nrf2 deficiency decreased fracture callus by using Nrf2 -knockout (KO) mice [ 55 ]. Moreover, Nrf2 can be involved in the control of excessive inflammatory responses [ 56 ], the promotion of osteogenesis in MSCs, and angiogenesis through VEGF expression [ 57 ], in early phase of fracture healing. In the remodeling phase, Nrf2 also regulates the balance of bone metabolism by suppressing oxidative stress-induced osteoclastogenesis [ 58 ].…”

Section: Bone Regenerationmentioning

confidence: 99%

The Role of Adipose Stem Cells in Bone Regeneration and Bone Tissue Engineering

Mende

Götzl

Kubo

et al. 2021

Cells

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Bone regeneration is a complex process that is influenced by tissue interactions, inflammatory responses, and progenitor cells. Diseases, lifestyle, or multiple trauma can disturb fracture healing, which might result in prolonged healing duration or even failure. The current gold standard therapy in these cases are bone grafts. However, they are associated with several disadvantages, e.g., donor site morbidity and availability of appropriate material. Bone tissue engineering has been proposed as a promising alternative. The success of bone-tissue engineering depends on the administered cells, osteogenic differentiation, and secretome. Different stem cell types offer advantages and drawbacks in this field, while adipose-derived stem or stromal cells (ASCs) are in particular promising. They show high osteogenic potential, osteoinductive ability, and immunomodulation properties. Furthermore, they can be harvested through a noninvasive process in high numbers. ASCs can be induced into osteogenic lineage through bioactive molecules, i.e., growth factors and cytokines. Moreover, their secretome, in particular extracellular vesicles, has been linked to fracture healing. The aim of this review is a comprehensive overview of ASCs for bone regeneration and bone tissue engineering.

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N‐Acetyl Cysteine Treatment Restores Early Phase Fracture Healing in Ethanol‐Fed Rats

Cited by 9 publications

References 41 publications

The Role of Oxidative Stress in Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies

The Role of Oxidative Stress in Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies

Understanding Reactive Oxygen Species in Bone Regeneration: A Glance at Potential Therapeutics and Bioengineering Applications

The Role of Adipose Stem Cells in Bone Regeneration and Bone Tissue Engineering

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