Toxicological and pharmacological concerns on oxidative stress and related diseases

Saeidnia, Soodabeh; Abdollahi, Mohammad

doi:10.1016/j.taap.2013.09.031

Cited by 225 publications

(131 citation statements)

References 139 publications

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“…Antioxidants were once thought to be beneficial for treating age-and obesity-associated metabolic derangements because excessive ROS accumulation was considered a cause of diverse pathologies, such as chronic inflammation, fibrotic damage, and insulin resistance (2,43,44). However, many animal and human clinical studies failed to show benefits of antioxidants in treating age-or obesity-associated diseases (12,14) and revealed several harmful side effects instead (45)(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species

Nam

Jang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Uncoupling protein 1 (Ucp1), which is localized in the mitochondrial inner membrane of mammalian brown adipose tissue (BAT), generates heat by uncoupling oxidative phosphorylation. Upon cold exposure or nutritional abundance, sympathetic neurons stimulate BAT to express Ucp1 to induce energy dissipation and thermogenesis. Accordingly, increased Ucp1 expression reduces obesity in mice and is correlated with leanness in humans. Despite this significance, there is currently a limited understanding of how Ucp1 expression is physiologically regulated at the molecular level. Here, we describe the involvement of Sestrin2 and reactive oxygen species (ROS) in regulation of Ucp1 expression. Transgenic overexpression of Sestrin2 in adipose tissues inhibited both basal and cold-induced Ucp1 expression in interscapular BAT, culminating in decreased thermogenesis and increased fat accumulation. Endogenous Sestrin2 is also important for suppressing Ucp1 expression because BAT from Sestrin2 −/− mice exhibited a highly elevated level of Ucp1 expression. The redox-inactive mutant of Sestrin2 was incapable of regulating Ucp1 expression, suggesting that Sestrin2 inhibits Ucp1 expression primarily through reducing ROS accumulation. Consistently, ROS-suppressing antioxidant chemicals, such as butylated hydroxyanisole and N-acetylcysteine, inhibited cold-or cAMP-induced Ucp1 expression as well. p38 MAPK, a signaling mediator required for cAMP-induced Ucp1 expression, was inhibited by either Sestrin2 overexpression or antioxidant treatments. Taken together, these results suggest that Sestrin2 and antioxidants inhibit Ucp1 expression through suppressing ROSmediated p38 MAPK activation, implying a critical role of ROS in proper BAT metabolism.aging | mouse | homeostasis | β-adrenergic signaling A lthough reactive oxygen species (ROS) are normal products of cellular metabolism, excessive accumulation of ROS resulting from nutritional imbalance and/or environmental stresses can provoke oxidative damage of diverse cellular macromolecules, such as DNA, RNA, and proteins (1). Accumulation of ROS has been associated with diverse degenerative diseases, such as cancer, neurodegeneration, and obesity-associated metabolic syndrome (2-4). To minimize detrimental consequences of ROS accumulation, cells are equipped with various antioxidant proteins, including superoxide dismutases, catalases, peroxiredoxins, and sestrins (5-7). Several ROS-scavenging chemicals or dietary supplements, such as butylated hydroxyanisole (BHA), N-acetylcysteine (NAC), and antioxidant vitamins, can assist with eliminating excessive amounts of ROS (8-10) and were once considered to be potential inhibitors of degenerative diseases associated with aging and obesity (11-13). However, most animal and human clinical studies failed to demonstrate the benefits of dietary antioxidants in restoring metabolic homeostasis or in promoting health and lifespan (13,14).Uncoupling protein 1 (Ucp1) is an anion-carrier protein located in the inner membrane of the mitochondria. By dissipatin...

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Section: Discussionmentioning

confidence: 99%

Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species

Nam

Jang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…ROS formation and oxidative stress may be the possible involved mechanisms in causing CNS related toxicities induced by benzene (Saeidnia and Abdollahi, 2013).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Current understandings and perspectives on non-cancer health effects of benzene: A global concern

Bahadar

Mostafalou

Abdollahi

2014

Toxicology and Applied Pharmacology

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“…Currently, there are approximately 381 million diabetic patients, a figure that expects to rise to 592 million by 2035 (1). Various studies have established the key role of oxidative stress in the pathophysiology of diabetes and its complications (2)(3)(4). Oxidative stress reflects an imbalance between the formation of reactive oxygen species (ROS) and body's antioxidant defense system (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Influence of Ascorbic Acid Supplementation on Type 2 Diabetes Mellitus in Observational and Randomized Controlled Trials; A Systematic Review with Meta-Analysis

et al. 2015

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-Purpose.There are controversial data regarding the beneficial effects of ascorbic acid (AA) supplementation in type 2 diabetes mellitus (T2DM). In this systematic review, we aimed to criticize the current relevant data from both observational and randomized controlled trials (RCTs). Methods. All observational and RCTs conducted to assess anti-hyperglycemic effects of AA in diabetics, published before January 2013, were included. To obtain all related studies Google Scholar, PubMed, Scopus, IranMedex, and Magiran web databases were searched. Exclusion criteria were animal studies, and studies conducted in Type 1 DM, children or pregnant women. Main outcome measures were fasting blood sugar (FBS), and glycated hemoglobin (HbA1c). According to degree of heterogeneity, fixed or random effect models were employed. Meta-analyses were done using Stats Direct software, version 3.0.97. The quality of included articles and publication bias were also assessed. Results. We selected 38 articles; 26 observational studies and 12 RCTs. Due to severe methodological heterogeneity in all observational studies and some of RCTs, we could pool data from only 5 RCTs in a meta-analysis. Single intake of AA versus placebo showed a significant effect on FBS; with the standardized mean difference (SMD): -20.59, 95% confidence intervals (95% CI): -40.77 to -0.4 (p= 0.04), but non-significant effect on HbA1c; SMD: -0.46, 95% CI: -1.75 to 0.84 (p= 0.4). Effect of other antioxidants with/without AA supplementation on FBSwere nonsignificant; SMD: -4.26 (p= 0.8), and SMD: -12.04 (p= 0.3), respectively. Also, their effect on HbA1c was non-significant; SMD: 0.53 (p= 0.11), and SMD: 0.28 (p= 0.34), respectively. Conclusions. Our study supports the positive effect of AA in reduction of FBS in diabetics, however, due to insufficient evidence ragarding long term safety of AA supplementation and limited number of RCTs, the long term use of this vitamin for its anti-diabetic properties cannot be strongly recommended.

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Toxicological and pharmacological concerns on oxidative stress and related diseases

Cited by 225 publications

References 139 publications

Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species

Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species

Current understandings and perspectives on non-cancer health effects of benzene: A global concern

Influence of Ascorbic Acid Supplementation on Type 2 Diabetes Mellitus in Observational and Randomized Controlled Trials; A Systematic Review with Meta-Analysis

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