Lupus

Research & Studies

The pathogenesis of systemic lupus erythematosus - From the viewpoint of oxidative stress and mitochondrial dysfunction

 

“SLE is characterized by an increased production of detrimental autoantigens, exaggerated effects of pro-inflammatory cytokines, dysregulated functioning of immunocompetent cells including lymphocytes and leukocytes, and devastating tissue and organ damage. All of these derangements can be potentiated or attenuated by the abnormal energy expenditure and overproduction of reactive oxygen species (ROS). There is accumulating data which support the importance of abnormal oxygen metabolism and mitochondrial disorders in the immunopathogenesis of SLE.”

 

Lee, H., Wu, T., Lin, C., Lee, C., Wei, Y., Tsai, C., & Chang, D. (2016). The pathogenesis of systemic lupus erythematosus - From the viewpoint of oxidative stress and mitochondrial dysfunction. Mitochondrion, 30, 1-7. doi: 10.1016/j.mito.2016.05.007

 

Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases

 

“Hydrogen has many advantages for therapeutic and preventive applications, and shows not only anti-oxidative stress effects, but also has various anti-inflammatory and anti-allergic effects. Preliminary clinical trials show that drinking hydrogen-dissolved water seems to improve the pathology of mitochondrial disorders.”

 

Ohta, S. (2012). Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases. Biochimica et Biophysica Acta, 1820(5), 586-594. doi: 10.1016/j.bbagen.2011.05.006

 

Mitochondrial dysfunction in T cells of patients with systemic lupus erythematosus

 

“T lymphocytes of patients with systemic lupus erythematosus (SLE) exhibit mitochondrial hyperpolarization, increased ROI production, diminished intracellular glutathione levels, cytoplasmic alkalinization, and ATP depletion that mediate enhanced spontaneous and diminished activation-induced apoptosis and sensitize lupus T cells to necrosis. These redox and metabolic checkpoints represent novel targets for pharmacological intervention in SLE.”

 

Perl, A., Gergely, P., & Banki, K. (2004). Mitochondrial dysfunction In T cells of patients with systemic lupus erythematosus. International Reviews of Immunology, 23(3-4), 293-313. doi: 10.1080/08830180490452576

 

Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventative and therapeutic applications

“H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. H2 prevented the decline of the mitochondrial membrane potential. This suggested that H2 protected mitochondria from OH. Along with this protective effect, H2 also prevented a decrease in the cellular level of ATP synthesized in mitochondria. The fact that H2 protected mitochondria and nuclear DNA provided evidence that H2 penetrated most membranes and diffused into organelles.”

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventative and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

 

Apoptosis and mitochondrial dysfunction in lymphocytes of patients with systemic lupus erythematosus

 

“Oxidative stress affects signaling through the T-cell receptor as well as the activity of redox-sensitive caspases. ATP depletion may be responsible for diminished activation-induced apoptosis and sensitize lupus T cells to necrosis. Mitochondrial dysfunction is identified as a key mechanism in the pathogenesis of SLE.”

 

Perl, A., Nagy, G., Gergely, P., Puskas, F., Qian, Y., & Banki, K. (2004). Apoptosis and mitochondrial dysfunction in lymphocytes of patients with systemic lupus erythematosus. Methods in Molecular Medicine, 102, 87-114. doi: 10.1385/1-59259-805-6:087

 

Hydrogen-rich saline protects against mitochondrial dysfunction and apoptosis in mice with obstructive jaundice

 

“HS markedly increased the antioxidant potential of mitochondria, as evidenced by elevated adenosine triphosphate levels, mitochondrial respiratory function, and increased levels of active Bcl‑2. In conclusion, HS attenuates mitochondrial oxidative stress and dysfunction, and inhibits mitochondrial-mediated apoptosis in the livers of BDL mice.”

 

Liu, Q., Li, B., Song, Y., Hu, M., Lu, J., Gao, A., . . . Liu, R. (2016). Hydrogen-rich saline protects against mitochondrial dysfunction and apoptosis in mice with obstructive jaundice. Molecular Medicine Reports, 13(4), 3588-3596. doi: 10.3892/mmr.2016.4954

 

Oxidative stress in the pathology and treatment of systemic lupus erythematosus

 

“Oxidative stress is increased in systemic lupus erythematosus (SLE), and it contributes to immune system dysregulation, abnormal activation and processing of cell-death signals, autoantibody production and fatal comorbidities. Mitochondrial dysfunction in T cells promotes the release of highly diffusible inflammatory lipid hydroperoxides, which spread oxidative stress to other intracellular organelles and through the bloodstream. Oxidative modification of self antigens triggers autoimmunity, and the degree of such modification of serum proteins shows striking correlation with disease activity and organ damage in SLE.”

 

Perl, A. (2013). Oxidative stress in the pathology and treatment of systemic lupus erythematosus. Nature Reviews Rheumatology, 9(11), 674-686. doi: 10.1038/nrrheum.2013.147

 

Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development and potential of hydrogen medicine

 

“The numerous publications on its biological and medical benefits revealed that H2 reduces oxidative stress not only by direct reactions with strong oxidants, but also indirectly by regulating various gene expressions. Moreover, by regulating the gene expressions, H2 functions as an anti-inflammatory and anti-apoptotic, and stimulates energy metabolism.”

 

Ohta, S. (2014). Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development and potential of hydrogen medicine. Pharmacology & Therapeutics, 144(1), 1-11. doi: 10.1016/j.pharmthera.2014.04.006

 

Oxidative stress and its biomarkers in systemic lupus erythematosus

 

“The uncontrolled oxidative stress in SLE contributes to functional oxidative modifications of cellular protein, lipid and DNA and consequences of oxidative modification play a crucial role in immunomodulation and trigger autoimmunity. Finally, this review also describes the reported clinical trials of antioxidant in the disease that have evaluated the efficacy of antioxidant in the management of disease with ongoing conventional therapy.”

 

Shah, D., Mahajan, N., Sah, S., Nath, S. K., & Paudyal, B. (2014). Oxidative stress and its biomarkers in systemic lupus erythematosus. Journal of Biomedical Science, 21(23), 1-13. doi: 10.1186/1423-0127-21-23

 

Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

 

Interaction between oxidative stress and chemokines: Possible pathogenic role in systemic lupus erythematosus and rheumatoid arthritis

 

“These results indicates that excessive production of ROS disturbs redox status and can modulate the expression of inflammatory chemokines leading to inflammatory processes, exacerbating inflammation and affecting tissue damage in autoimmune diseases, as exemplified by their strong association with disease activity.”

 

Shah, D., Wanchu, A., & Bhatnagar, A. (2011). Interaction between oxidative stress and chemokines: Possible pathogenic role in systemic lupus erythematosus and rheumatoid arthritis. Immunobiology, 216(9), 1010-1017. doi: 10.1016/j.imbio.2011.04.001

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602

 

Oxidative stress, T cell DNA methylation, and lupus

 

“Our findings indicate that oxidative stress may contribute to human lupus flares by inhibiting ERK pathway signaling in T cells to decrease DNMT-1 and cause DNA demethylation.”

 

Li, Y., Gorelik, G., Strickland, F. M., & Richardson, B. C. (2014). Oxidative stress, T cell DNA methylation, and lupus. Arthritis & Rheumatology, 66(6), 1574-1582. doi: 10.1002/art.38427

 

The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance

 

“Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell.”

 

Dixon, B. J., Tang, J., & Zhang, J. H. (2013). The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance. Medical Gas Research, 3(10), 1-12. doi: 10.1186/2045-9912-3-10

 

Increased levels of autoantibodies against catalase and superoxide dismutase associated with oxidative stress in patients with rheumatoid arthritis and systemic lupus erythematosus

 

“Collectively, these results suggested that the primary factor causing the oxidative stress observed in RA and SLE is excessive free radical production rather than impaired CAT or SOD activity due to autoantibody inhibition.”

 

Mansour, R. B., Lassoued, S., Gargouri, B., Gaïd, A. E., Attia, H., & Fakhfakh, F. (2008). Increased levels of autoantibodies against catalase and superoxide dismutase associated with oxidative stress in patients with rheumatoid arthritis and systemic lupus erythematosus. Scandinavian Journal of Rheumatology, 37(2), 103-108. doi: 10.1080/03009740701772465

 

A review of hydrogen as a new medical therapy

 

“In the past few years many initial and subsequent clinical studies have demonstrated that hydrogen can act as an important physiological regulatory factor to cells and organs on the antioxidant, anti-inflammatory, anti-apoptotic and other protective effects. So far several delivery methods applied in these studies have proved to be available and convenient, including inhalation, drinking hydrogen-dissolved water and injection with hydrogen-saturated saline.”

 

Zhang, J., Liu, C., Zhou, L., Qu, K., Wang, R., Tai, M., . . . Wang, Z. (2012). A Review of hydrogen as a new medical therapy. Hepatogastroenterology, 59(116), 1026-1032. doi: 10.5754/hge11883

 

Oxidative Stress and treg and th17 dysfunction in systemic lupus erythematosus

 

“Altogether, these data suggest that antioxidant drug might be promising therapeutic methods for the treatment of SLE, and the specific therapeutic mechanism needs to be further studied. Taken together, these data show that oxidative stress plays a key role in the pathogenesis of SLE. Oxidative stress can induce and aggravate SLE by linking environmental stimulation with immune imbalance.”

 

Yang, J., Yang, X., Zou, H., & Li, M. (2016). Oxidative stress and treg and th17 dysfunction in systemic lupus erythematosus. Oxidative Medicine and Cellular Longevity, 2016(2526174), 1-9. doi: 10.1155/2016/2526174

 

Hydrogen resuscitation, a new cytoprotective approach

 

“Recent evidence indicates that hydrogen is a potent anti-oxidative, anti-apoptotic and anti-inflammatory agent and so may have potential medical application. Studies have shown that hydrogen resuscitation has cytoprotective effects in different cell types and disease models, including ischaemia-reperfusion injury, inflammation, toxicity, trauma and metabolic disease. The underlying mechanism may be the selective elimination of hydroxyl radicals, although other mechanisms may also be involved (e.g. hydrogen functioning as a gaseous signalling molecule). Hydrogen resuscitation may have several potential advantages over current pharmacological therapies for oxidative injuries.”

 

Zheng, X., Sun, X., & Xia, Z. (2011). Hydrogen resuscitation, a new cytoprotective approach. Clinical and Experimental Pharmacology and Physiology, 38(3), 155-163. doi: 10.1111/j.1440-1681.2011.05479.x

 

Markers of oxidative and nitrosative stress in systemic lupus erythematosus: Correlation with disease activity

 

“These findings support an association between oxidative/nitrosative stress and SLE. The stronger response observed in serum samples from patients with higher SLEDAI scores suggests that markers of oxidative/nitrosative stress may be useful in evaluating the progression of SLE and in elucidating the mechanisms of disease pathogenesis.”

 

Wang, G., Pierangeli, S. S., Papalardo, E., Ansari, G., & Khan, M. F. (2010). Markers of oxidative and nitrosative stress in systemic lupus erythematosus: Correlation with disease activity. Arthritis & Rheumatism, 62(7), 2064-2072. doi: 10.1002/art.27442

 

Treatment with hydrogen-rich saline delays disease progression in a mouse model of amyotrophic lateral sclerosis

 

“In conclusion, hydrogen molecule may be neuroprotective against ALS, possibly through abating oxidative and nitrosative stress and preserving mitochondrial function.”

 

Zhang, Y., Li, H., Yang, C., Fan, D., Guo, D., Hu, H., . . . Pan, S. (2015). Treatment with hydrogen-rich saline delays disease progression in a mouse model of amyotrophic lateral sclerosis. Neurochemical Research, 41(4), 770-778. doi: 10.1007/s11064-015-1750-7

 

Mechanisms of disease for the clinician: Systemic lupus erythematosus

 

“The recognition and diagnosis of SLE are important for the practicing physician to understand immunology, pathogenesis, laboratory evaluation, and updated treatment options. Many other signs, symptoms, and conditions can masquerade as SLE. Symptoms vary from person to person, may be intermittent, and can be mild, moderate, or severe.”

 

Frieri, M. (2013). Mechanisms of disease for the clinician: Systemic lupus erythematosus. Annals of Allergy, Asthma & Immunology, 110(4), 228-232. doi: 10.1016/j.anal.2012.12.010

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