Inhibition of skin fibrosis in systemic sclerosis by botulinum toxin B via the suppression of oxidative stress

Baral, Hritu; Sekiguchi, Akiko; Uchiyama, Akihiko; Amalia, Syahla Nisaa; Yamazaki, Sunao; Inoue, Yuta; Yokoyama, Yoko; Ogino, Sachiko; Torii, Ryoko; Hosoi, Mari; Akai, Ryoko; Ishikawa, Osamu; Motegi, Sei‐ichiro

doi:10.1111/1346-8138.15888

Cited by 5 publications

(3 citation statements)

References 57 publications

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“…Several human skin pathologies, including SSc, are associated with significant redox imbalance at the cellular level [13,[47][48][49]. Antioxidant administration has also been reported to suppress skin and pulmonary fibrosis in SSc [50][51][52]. One example is Edaravone a novel, free radical scavenger and neuroprotective agent used in the treatment of acute Several human skin pathologies, including SSc, are associated with significant redox imbalance at the cellular level [13,[47][48][49].…”

Section: Inhibition Of Hocl-induced Skin and Lung Fibrosis By Twxmentioning

confidence: 99%

The Potential of Twendee X® as a Safe Antioxidant Treatment for Systemic Sclerosis

You,

Nicco,

Harakawa

et al. 2024

IJMS

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Systemic sclerosis (SSc) is an autoimmune disease characterized by systemic skin hardening, which combines Raynaud’s phenomenon and other vascular disorders, skin and internal organ fibrosis, immune disorders, and a variety of other abnormalities. Symptoms vary widely among individuals, and personalized treatment is sought for each patient. Since there is no fundamental cure for SSc, it is designated as an intractable disease with patients receiving government subsidies for medical expenses in Japan. Oxidative stress (OS) has been reported to play an important role in the cause and symptoms of SSc. HOCl-induced SSc mouse models are known to exhibit skin and visceral fibrosis, vascular damage, and autoimmune-like symptoms observed in human SSc. The antioxidant combination Twendee X® (TwX) is a dietary supplement consisting of vitamins, amino acids, and CoQ10. TwX has been proven to prevent dementia in humans with mild cognitive impairment and significantly improve cognitive impairment in an Alzheimer’s disease mouse model by regulating OS through a strong antioxidant capacity that cannot be achieved with a single antioxidant ingredient. We evaluated the effectiveness of TwX on various symptoms of HOCl-induced SSc mice. TwX-treated HOCl-induced SSc mice showed significantly reduced lung and skin fibrosis compared to untreated HOCl-induced SSc mice. TwX also significantly reduced highly oxidized protein products (AOPP) in serum and suppressed Col-1 gene expression and activation of B cells involved in autoimmunity. These findings suggest that TwX has the potential to be a new antioxidant treatment for SSc without side effects.

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Section: Inhibition Of Hocl-induced Skin and Lung Fibrosis By Twxmentioning

confidence: 99%

The Potential of Twendee X® as a Safe Antioxidant Treatment for Systemic Sclerosis

You,

Nicco,

Harakawa

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…One example is Edaravone a novel, free radical scavenger and neuroprotective agent used in the treatment of acute Several human skin pathologies, including SSc, are associated with significant redox imbalance at the cellular level [13,[47][48][49]. Antioxidant administration has also been reported to suppress skin and pulmonary fibrosis in SSc [50][51][52]. One example is Edaravone, a novel, free radical scavenger and neuroprotective agent used in the treatment of acute embolic stroke in humans [53].…”

Section: Inhibition Of Hocl-induced Skin and Lung Fibrosis By Twxmentioning

confidence: 99%

The Potential of Twendee X®︎ as a Safe Antioxidant Treatment for Systemic Sclerosis

You,

Nicco,

Harakawa

et al. 2024

Preprint

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Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by debilitating symptoms including skin and visceral fibrosis, systemic skin hardening, Raynaud's phenomenon and other vascular dysfunctions, and immune abnormalities. The disease poses a significant medical challenge with no cure currently available. As such, SSc is designated as an intractable disease in Japan, with patients receiving government subsidies for medical expenses. Oxidative stress (OS) is implicated in the pathogenesis of SSc and the antioxidant combination Tweendee X®︎ (TwX) has shown promising results in mitigating OS-related conditions. HOCl-induced SSc-mice are known to exhibit similar skin and visceral fibrosis, vascular disorders, and autoimmunity observed in human. In a study done using these mice, Twx demonstrated a significant reduction in lung and skin fibrosis compared to untreated HOCl-induced SSc mice. TwX also significantly reduced advanced oxidized protein products (AOPP) in serum, Col-1 gene expression and the activation of B cells involved in autoimmunity. SSc is a disease state in which autoimmune abnormalities, fibrosis, and vascular disorders are intertwined, and therefore for a treatment to be effective it needs to address multiple issues. Thus the efficacy of TwX may stem from its strong antioxidant capacity to regulate OS, which cannot be achieved by a single antioxidant on its own. In other studies, targeting other OS-related conditions, TwX was safe and proved to be effective at prevent dementia in humans with mild cognitive impairment and to significantly improve cognitive impairment in Alzheimer's (AD) mouse models. TwX may offer a new approach to antioxidant treatment for SSc, to address multiple abnormalities that are characteristic of the disease.

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“…[ 12 , 14 , 15 ], epilepsy [ 16 ], Huntington’s disease [ 17 , 18 ], diabetes mellitus [ 19 ], and multiple organ dysfunction syndrome [ 20 ]. In addition to that, oxidative stress is associated with mechanisms of psoriasis development [ 21 , 22 , 23 , 24 ] and with skin fibrosis in systemic scleroderma [ 25 ]. Oxidative stress, which is primarily caused by mitochondrial dysfunction, plays one of the leading roles in the processes of aging, both in tissues and in the whole organism [ 5 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Antioxidant Gene Overexpression on Stress Resistance and Malignization In Vitro and In Vivo: A Review

et al. 2022

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Reactive oxygen species (ROS) are normal products of a number of biochemical reactions and are important signaling molecules. However, at the same time, they are toxic to cells and have to be strictly regulated by their antioxidant systems. The etiology and pathogenesis of many diseases are associated with increased ROS levels, and many external stress factors directly or indirectly cause oxidative stress in cells. Within this context, the overexpression of genes encoding the proteins in antioxidant systems seems to have become a viable approach to decrease the oxidative stress caused by pathological conditions and to increase cellular stress resistance. However, such manipulations unavoidably lead to side effects, the most dangerous of which is an increased probability of healthy tissue malignization or increased tumor aggression. The aims of the present review were to collect and systematize the results of studies devoted to the effects resulting from the overexpression of antioxidant system genes on stress resistance and carcinogenesis in vitro and in vivo. In most cases, the overexpression of these genes was shown to increase cell and organism resistances to factors that induce oxidative and genotoxic stress but to also have different effects on cancer initiation and promotion. The last fact greatly limits perspectives of such manipulations in practice. The overexpression of GPX3 and SOD3 encoding secreted proteins seems to be the “safest” among the genes that can increase cell resistance to oxidative stress. High efficiency and safety potential can also be found for SOD2 overexpression in combinations with GPX1 or CAT and for similar combinations that lead to no significant changes in H2O2 levels. Accumulation, systematization, and the integral analysis of data on antioxidant gene overexpression effects can help to develop approaches for practical uses in biomedical and agricultural areas. Additionally, a number of factors such as genetic and functional context, cell and tissue type, differences in the function of transcripts of one and the same gene, regulatory interactions, and additional functions should be taken into account.

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Inhibition of skin fibrosis in systemic sclerosis by botulinum toxin B via the suppression of oxidative stress

Cited by 5 publications

References 57 publications

The Potential of Twendee X® as a Safe Antioxidant Treatment for Systemic Sclerosis

The Potential of Twendee X® as a Safe Antioxidant Treatment for Systemic Sclerosis

The Potential of Twendee X®︎ as a Safe Antioxidant Treatment for Systemic Sclerosis

Effects of Antioxidant Gene Overexpression on Stress Resistance and Malignization In Vitro and In Vivo: A Review

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