Antioxidant Properties of Alpha-Lipoic (Thioctic) Acid Treatment on Renal and Heart Parenchyma in a Rat Model of Hypertension

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Abstract

Renal and cardiac impairments are frequent events in the presence of hypertension. Organ damage is mainly linked to oxidative stress due to high blood pressure and may be reduced by antioxidant supplementation. Alpha-lipoic acid (ALA) is one of most effective antioxidants. It is widely used as a nutritional supplement in a racemic mixture (+/–), even though the (+)-enantiomer is biologically active. This study was designed to investigate the effect of treatment with (+/–)-ALA and its enantiomers on renal and heart parenchyma in spontaneously hypertensive rats (SHR), using immunochemical and immunohistochemical techniques. The results confirmed that the oxidative mechanisms of organ alterations, due to hypertension, and characterized by glomerular and tubular lesions, left ventricular hypertrophy, and fibrosis but not by apoptosis were accompanied by proteins’ and nucleic acids’ oxidation. We found greater effectiveness of (+)-ALA compared to (+/−)-ALA in reducing oxidative stress, cardiac and renal damages in SHR. To conclude, these data propose (+)-ALA as one of the more appropriate antioxidant molecules to prevent renal and cardiac alterations associated with hypertension.

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Physiological and pathological cardiac hypertrophy.

Ippei Shimizu, Tohru Minamino (2016)

The heart must continuously pump blood to supply the body with oxygen and nutrients. To maintain the high energy consumption required by this role, the heart is equipped with multiple complex biological systems that allow adaptation to changes of systemic demand. The processes of growth (hypertrophy), angiogenesis, and metabolic plasticity are critically involved in maintenance of cardiac homeostasis. Cardiac hypertrophy is classified as physiological when it is associated with normal cardiac function or as pathological when associated with cardiac dysfunction. Physiological hypertrophy of the heart occurs in response to normal growth of children or during pregnancy, as well as in athletes. In contrast, pathological hypertrophy is induced by factors such as prolonged and abnormal hemodynamic stress, due to hypertension, myocardial infarction etc. Pathological hypertrophy is associated with fibrosis, capillary rarefaction, increased production of pro-inflammatory cytokines, and cellular dysfunction (impairment of signaling, suppression of autophagy, and abnormal cardiomyocyte/non-cardiomyocyte interactions), as well as undesirable epigenetic changes, with these complex responses leading to maladaptive cardiac remodeling and heart failure. This review describes the key molecules and cellular responses involved in physiological/pathological cardiac hypertrophy.

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Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential.

Kate Shay, Régis Moreau, Eric Smith … (2009)

Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well-defined as a therapy for preventing diabetic polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age. How do the biochemical properties of LA relate to its biological effects? Herein, we review the molecular mechanisms of LA discovered using cell and animal models, and the effects of LA on human subjects. Though LA has long been touted as an antioxidant, it has also been shown to improve glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa B. LA and its reduced form, dihydrolipoic acid, may use their chemical properties as a redox couple to alter protein conformations by forming mixed disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting that some of its therapeutic potential extends beyond the strict definition of an antioxidant. Current trials are investigating whether these beneficial properties of LA make it an appropriate treatment not just for diabetes, but also for the prevention of vascular disease, hypertension, and inflammation.

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Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance?

Rhian M. Touyz (2004)

Metabolism of oxygen by cells generates potentially deleterious reactive oxygen species (ROS). Under normal conditions the rate and magnitude of oxidant formation is balanced by the rate of oxidant elimination. However, an imbalance between prooxidants and antioxidants results in oxidative stress, which is the pathogenic outcome of oxidant overproduction that overwhelms the cellular antioxidant capacity. The kidney and vasculature are rich sources of NADPH oxidase-derived ROS, which under pathological conditions play an important role in renal dysfunction and vascular damage. Strong experimental evidence indicates that increased oxidative stress and associated oxidative damage are mediators of renovascular injury in cardiovascular pathologies. Increased production of superoxide anion and hydrogen peroxide, reduced nitric oxide synthesis, and decreased bioavailability of antioxidants have been demonstrated in experimental and human hypertension. These findings have evoked considerable interest because of the possibilities that therapies targeted against free radicals by decreasing ROS generation or by increasing nitric oxide availability and antioxidants may be useful in minimizing vascular injury and renal dysfunction and thereby prevent or regress hypertensive end-organ damage. This article highlights current developments in the field of ROS and hypertension, focusing specifically on the role of oxidative stress in hypertension-associated vascular damage. In addition, recent clinical trials investigating cardiovascular benefits of antioxidants are discussed, and some explanations for the rather disappointing results from these studies are addressed. Finally, important avenues for future research in the field of ROS, oxidative stress, and redox signaling in hypertension are considered.

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Author and article information

Contributors

Silvana Hrelia: Role: Academic Editor

Cristina Angeloni: Role: Academic Editor

Journal

Journal ID (nlm-ta): Antioxidants (Basel)

Journal ID (iso-abbrev): Antioxidants (Basel)

Journal ID (publisher-id): antioxidants

Title: Antioxidants

Publisher: MDPI

ISSN (Electronic): 2076-3921

Publication date (Electronic): 23 June 2021

Publication date Collection: July 2021

Volume: 10

Issue: 7

Electronic Location Identifier: 1006

Affiliations

[1 ]School of Pharmacy, University of Camerino, 62032 Camerino, Italy; ilenia.martinelli@ 123456unicam.it (I.M.); francesco.amenta@ 123456unicam.it (F.A.)

[2 ]School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy; daniele.tomassoni@ 123456unicam.it (D.T.); proshanta.roy@ 123456unicam.it (P.R.)

[3 ]Department of Neuroscience, Pharmaceutical and Child Health Area (NEUROFARBA), University of Florence, 50139 Florence, Italy; lorenzo.mannelli@ 123456unifi.it

Author notes

[* ]Correspondence: khosrow.tayebati@ 123456unicam.it

[†]

These authors contributed equally to this work.

Author information

Ilenia Martinelli https://orcid.org/0000-0002-7702-7784

Daniele Tomassoni https://orcid.org/0000-0001-9062-3305

Lorenzo Di Cesare Mannelli https://orcid.org/0000-0001-8374-4432

Francesco Amenta https://orcid.org/0000-0002-0555-1034

Seyed Khosrow Tayebati https://orcid.org/0000-0002-7219-6917

Article

Publisher ID: antioxidants-10-01006

DOI: 10.3390/antiox10071006

PMC ID: 8300705

PubMed ID: 34201726

SO-VID: 2adf91dc-f1f2-4e66-99af-e3bc810b84d7

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

Antioxidant Properties of Alpha-Lipoic (Thioctic) Acid Treatment on Renal and Heart Parenchyma in a Rat Model of Hypertension

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Karger: Nephrology

Most cited references 84

Physiological and pathological cardiac hypertrophy.

Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential.

Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance?

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