Potential Therapeutic Applications of MnSODs and SOD‐Mimetics

Bonetta, Rosalin

doi:10.1002/chem.201704561

Cited by 94 publications

(91 citation statements)

References 117 publications

(287 reference statements)

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“…The antioxidative system, mainly SOD and other enzymes, is used to balance the ROS generation and scavenging . The Cu/Zn‐SOD mainly existed in cytoplasm, and the Mn‐SOD mainly situated in mitochondria.…”

Section: Resultsmentioning

confidence: 96%

Sirtuin3 deficiency exacerbates carbon tetrachloride−induced hepatic injury in mice

Shen

et al. 2018

J Biochem & Molecular Tox

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Sirtuin3 (SIRT3) plays an important role in maintaining normal mitochondrial function and alleviating oxidative stress. After carbon tetrachloride (CCl 4 ) administration, the expression of SIRT3 decreased in the liver of mice, which indicated that the SIRT3 might play a crucial role during chemical-induced acute hepatic injury. To verify the hypothesis, CCl 4 was given to induce acute hepatic injury in SIRT3 knockout (KO) mice and wild-type (WT) mice. CCl 4 -induced liver injury was more severe in SIRT3 KO mice compared with the WT mice. In addition, the oxidative stress induced by CCl 4 was enhanced in the SIRT3 KO mice. Furthermore, the increased expression of dynamin-related protein 1 was also aggravated in SIRT3 KO mice after CCl 4 administration. In conclusion, our study demonstrated that SIRT3 deficiency exacerbated CCl 4 -induced impairment of the liver in mice, and the mechanism might be related to enhanced oxidative stress. K E Y W O R D Scarbon tetrachloride (CCl 4 ), liver, oxidative stress, sirtuin3 (SIRT3)

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Section: Resultsmentioning

confidence: 96%

Sirtuin3 deficiency exacerbates carbon tetrachloride−induced hepatic injury in mice

Shen

et al. 2018

J Biochem & Molecular Tox

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“…Theses cisplatin doses were lethal and prevented the study of late effects. The main limitations of using native SOD enzymes have been large size (>30 kDa), high manufacturing cost of recombinant enzymes, bell-shape dose-response curves, low cell permeability, antigenicity, and short circulating half-life [48] . Additionally, drawbacks of the non-specific SOD mimics include off-target effects, making it challenging to understand the specific role of O 2 •- in cisplatin-induced AKI.…”

Section: Discussionmentioning

confidence: 99%

Persistent increase in mitochondrial superoxide mediates cisplatin-induced chronic kidney disease

et al. 2019

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Severe and recurrent cisplatin-induced acute kidney injury (AKI) as part of standard cancer therapy is a known risk factor for development of chronic kidney disease (CKD). The specific role of superoxide (O2•-)-mediated disruption of mitochondrial oxidative metabolism in CKD after cisplatin treatment is unexplored. Cisplatin is typically administered in weekly or tri-weekly cycles as part of standard cancer therapy. To investigate the role of O2•- in predisposing patients to future renal injury and in CKD, mice were treated with cisplatin and a mitochondrial-specific, superoxide dismutase (SOD) mimetic, GC4419. Renal function, biomarkers of oxidative stress, mitochondrial oxidative metabolism, and kidney injury markers, as well as renal histology, were assessed to evaluate the cellular changes that occur one week and one month (CKD phase) after the cisplatin insult. Cisplatin treatment resulted in persistent upregulation of kidney injury markers, increased steady-state levels of O2•-, increased O2•--mediated renal tubules damage, and upregulation of mitochondrial electron transport chain (ETC) complex I activity both one week and one month following cisplatin treatment. Treatment with a novel, clinically relevant, small-molecule superoxide dismutase (SOD) mimetic, GC4419, restored mitochondrial ETC complex I activity to control levels without affecting complexes II–IV activity, as well as ameliorated cisplatin-induced kidney injury. These data support the hypothesis that increased mitochondrial O2•- following cisplatin administration, as a result of disruptions of mitochondrial metabolism, may be an important contributor to both AKI and CKD progression.

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“…Dietary and natural antioxidants from various sources and vitamins are still popular agents for clinical trials, and melatonin is emerging as a potential therapy for type 2 diabetes. Pharmaceuticals targeting prooxidant and antioxidant enzymes, such as NADPH oxidase inhibitors, xanthine oxidase inhibitors, and SOD mimetics, are actively being developed for the treatment of oxidative stress-related diseases, including type 2 diabetes [99,100].…”

Section: Oxidative Stress In Patients With Type 2 Diabetesmentioning

confidence: 99%

Can antioxidants be effective therapeutics for type 2 diabetes?

Park

2021

Yeungnam Univ J Med

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Although reactive oxygen species (ROS) are produced as a byproduct of oxygen metabolism, they play a significant role in normal cellular functions [1,2]. A well-organized antioxidant system maintains the physiological levels of ROS [3]. However, an imbalance between ROS production and antioxidant capacity causes ROS accumulation, which induces chemical modifications of DNA, protein, and lipids, leading to cellular damage, known as oxidative stress [1-3]. Oxidative stress is closely linked to a variety of diseases, including type 2 diabetes [1]. Type 2 diabetes is increasing globally due to the obesity pandemic and the growth of the aging population, and insulin resistance is a critical link between these two. Insulin resistance is known to be a critical risk factor for type 2 diabetes and other chronic diseases, such as cardiovascular diseases and cancers [4]. It is known that hyperglycemia in diabetic patients leads to se

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Potential Therapeutic Applications of MnSODs and SOD‐Mimetics

Cited by 94 publications

References 117 publications

Sirtuin3 deficiency exacerbates carbon tetrachloride−induced hepatic injury in mice

Sirtuin3 deficiency exacerbates carbon tetrachloride−induced hepatic injury in mice

Persistent increase in mitochondrial superoxide mediates cisplatin-induced chronic kidney disease

Can antioxidants be effective therapeutics for type 2 diabetes?

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