Lipoic Acid as a Potential Therapy for Chronic Diseases Associated with Oxidative Stress

Smith, Andrew; Shenvi, Swapna; Widlansky, Michael E.; Suh, Ji-Yeon; Hagen, Tory M.

doi:10.2174/0929867043365387

Cited by 420 publications

(315 citation statements)

References 0 publications

Supporting

Mentioning

295

Contrasting

Unclassified

Order By: Relevance

“…Lipoic acid is another example of an "endogenous" substrate also available through the diet as a dietary antioxidant supplement (Bustamante et al, 1998) and as a therapeutic agent (Smith et al, 2004). Lipoic acid is a cofactor for α-ketoglutarate and pyruvate dehydrogenases.…”

Section: Nitrogen-containing Endogenous Substrates-mentioning

confidence: 99%

Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism

Krueger

Williams

2005

Pharmacology & Therapeutics

515

444

View full text Add to dashboard Cite

Flavin-containing monooxygenase (FMO) oxygenates drugs and xenobiotics containing a "softnucleophile", usually nitrogen or sulfur. FMO, like cytochrome P450 (CYP), is a monooxygenase, utilizing the reducing equivalents of NADPH to reduce 1 atom of molecular oxygen to water, while the other atom is used to oxidize the substrate. FMO and CYP also exhibit similar tissue and cellular location, molecular weight, substrate specificity, and exist as multiple enzymes under developmental control. The human FMO functional gene family is much smaller (5 families each with a single member) than CYP. FMO does not require a reductase to transfer electrons from NADPH and the catalytic cycle of the 2 monooxygenases is strikingly different. Another distinction is the lack of induction of FMOs by xenobiotics.In general, CYP is the major contributor to oxidative xenobiotic metabolism. However, FMO activity may be of significance in a number of cases and should not be overlooked. FMO and CYP have overlapping substrate specificities, but often yield distinct metabolites with potentially significant toxicological/pharmacological consequences.The physiological function(s) of FMO are poorly understood. Three of the 5 expressed human FMO genes, FMO1, FMO2 and FMO3, exhibit genetic polymorphisms. The most studied of these is FMO3 (adult human liver) in which mutant alleles contribute to the disease known as trimethylaminuria. The consequences of these FMO genetic polymorphisms in drug metabolism and human health are areas of research requiring further exploration.

show abstract

Section: Nitrogen-containing Endogenous Substrates-mentioning

confidence: 99%

Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism

Krueger

Williams

2005

Pharmacology & Therapeutics

515

444

View full text Add to dashboard Cite

show abstract

“…Thus various therapies and strategies have been suggested [120][121][122][123][124][125][126][127] (Table 1). Simultaneously countless reports are there in literature for supplement of various antioxidants.…”

Section: Reactive Oxygen Species and Reactive Nitrogen Species Transimentioning

confidence: 99%

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

Singh

Chandra

Mahdi

et al. 2010

Indian J Clin Biochem

View full text Add to dashboard Cite

The antioxidants are essential molecules in human system but are not miracle molecules. They are neither performance enhancers nor can prevent or cure diseases when taken in excess. Their supplemental value is debateable. In fact, many high quality clinical trials on antioxidant supplement have shown no effect or adverse outcomes ranging from morbidity to all cause mortality. Several Chochrane Meta-analysis and Markov Model techniques, which are presently best available statistical models to derive conclusive answers for comparing large number of trials, support these claims. Nevertheless none of these statistical techniques are flawless. Hence, more efforts are needed to develop perfect statistical model to analyze the pooled data and further double blind, placebo controlled interventional clinical trials, which are gold standard, should be implicitly conducted to get explicit answers. Superoxide dismutase (SOD), glutathione peroxidase and catalase are termed as primary antioxidants as these scavenge superoxide anion and hydrogen peroxide. All these three enzymes are inducible enzymes, thereby inherently meaning that body increases or decreases their activity as per requirement. Hence there is no need to attempt to manipulate their activity nor have such efforts been clinically useful. SOD administration has been tried in some conditions especially in cancer and myocardial infarction but has largely failed, probably because SOD is a large molecule and can not cross cell membrane. The dietary antioxidants, including nutrient antioxidants are chain breaking antioxidants and in tandem with enzyme antioxidants temper the reactive oxygen species (ROS) and reactive nitrogen species (RNS) within physiological limits. Since body is able to regulate its own requirements of enzyme antioxidants, the diet must provide adequate quantity of non-enzymic antioxidants to meet the normal requirements and provide protection in exigent condition. So far, there is no evidence that human tissues ever experience the torrent of reactive species and that in chronic conditions with mildly enhanced generation of reactive species, the body can meet them squarely if antioxidants defense system in tissues is biochemically optimized. We are not yet certain about optimal levels of antioxidants in tissues. Two ways have been used to assess them: first by dietary intake and second by measuring plasma levels. Lately determination of plasma/serum level of antioxidants is considered better index for diagnostic and prognostic purposes. The recommended levels for vitamin A, E and C and beta carotene are 2.2-2.8 lmol/l; 27.5-30 lmol/l; 40-50 lmol/l and 0.4-0.5 lmol/l, respectively. The requirement and recommended blood levels of other dietary antioxidants are not established. The resolved issues are (1) essential to scavenge excess of radical species (2) participants in redox homeostasis (3) selective antioxidants activity against radical species (4) there is no universal antioxidant and 5) therapeutic value in case of deficiency. The overar...

show abstract

“…In vitro studies suggest that LA fits well into this standard definition. Because of its juxtaposed thiol groups and a high reduction potential of the DHLA/LA redox pair (2320 mV), LA and DHLA are capable of scavenging a variety of ROS and RNS (1,2). However, most of the evidence that support (DH)LA as a direct scavenger of ROS/RNS mainly comes from in vitro studies and there is little direct support that LA acts as a physiological antioxidant.…”

Section: La As a Direct-acting Antioxidantmentioning

confidence: 99%

“…Based largely on in vitro studies, LA has been touted as a potent biological antioxidant, that is, LA or dihydrolipoic acid (DHLA) terminates a number of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and also chelates redox active transition metals (e.g. iron, copper) (1,2). This salutary antioxidant role has been implicated as part of the mechanism underlying the clinical benefits for orally supplied LA as a diabetes medicine and its means to improve age-associated cardiovascular, cognitive, and neuromuscular declines in animal models (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Is α‐lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity

et al. 2008

View full text Add to dashboard Cite

SummaryThe chemical reduction and oxidation (redox) properties of a-lipoic acid (LA) suggest that it may have potent antioxidant potential. A significant number of studies now show that LA and its reduced form, dihydrolipoic acid (DHLA), directly scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) species and protect cells against a host of insults where oxidative stress is part of the underlying etiology. However, owing to its limited and transient accumulation in tissues following oral intake, the efficacy of nonprotein-bound LA to function as a physiological antioxidant has been questioned. Herein, we review the evidence that the micronutrient functions of LA may be more as an effector of important cellular stress response pathways that ultimately influence endogenous cellular antioxidant levels and reduce proinflammatory mechanisms. This would promote a sustained improvement in cellular resistance to pathologies where oxidative stress is involved, which would not be forthcoming if LA solely acted as a transient ROS scavenger.

show abstract

Lipoic Acid as a Potential Therapy for Chronic Diseases Associated with Oxidative Stress

Cited by 420 publications

References 0 publications

Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism

Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

Is α‐lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity

Contact Info

Product

Resources

About