Cited by 102Antioxidant Activity and Oxidative StressRedox biology and oxidative stressNitric Oxide and Endothelin Effects

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Detrimental Effects of Lipid Peroxidation in Type 2 Diabetes: Exploring the Neutralizing Influence of Antioxidants

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Shabalala, Samukelisiwe C., Johnson, Rabia, Basson, Albertus K., Ziqubu, Khanyisani, Hlengwa, Nokulunga, Mthembu, Sinenhlanhla X. H., Mabhida, Sihle E., Mazibuko-Mbeje, Sithandiwe E., Hanser, Sidney, Cirilli, Ilenia, Tiano, Luca, Dludla, Phiwayinkosi V.·2022·Antioxidants

DOI 10.3390/antiox11102071PMC PMC9598619

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Abstract

Lipid peroxidation, including its prominent byproducts such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE), has long been linked with worsened metabolic health in patients with type 2 diabetes (T2D). In fact, patients with T2D already display increased levels of lipids in circulation, including low-density lipoprotein-cholesterol and triglycerides, which are easily attacked by reactive oxygen molecules to give rise to lipid peroxidation. This process severely depletes intracellular antioxidants to cause excess generation of oxidative stress. This consequence mainly drives poor glycemic control and metabolic complications that are implicated in the development of cardiovascular disease. The current review explores the pathological relevance of elevated lipid peroxidation products in T2D, especially highlighting their potential role as biomarkers and therapeutic targets in disease severity. In addition, we briefly explain the implication of some prominent antioxidant enzymes/factors involved in the blockade of lipid peroxidation, including termination reactions that involve the effect of antioxidants, such as catalase, coenzyme Q10, glutathione peroxidase, and superoxide dismutase, as well as vitamins C and E.

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Figure 1 An overview of pathological mechanisms of lipid peroxidation, especially highlighting the formation of lipid aldehydes. Briefly, the different steps, indicate (➀) Initiation, (➁) Propagation (➂) termination, and (➃) formation ACR, MDA and 4-HNE. Abbreviations; PUFA: polyunsaturated fatty acid; ROS: reactive oxygen species; MDA: malondialdehyde; 4-HNE: 4-hydroxy-2-nonenal; •OH: hydroxyl radical; LO•: lipid alkoxyl radical; LOO•: lipid peroxyl radical; LOOH: lipid hydroperoxide. NB: Yellow dot indicated a point where oxidation occurs.CC BY · PubMed Central

Figure 2 A general overview of the prominent mechanisms and makers of lipid peroxidation such as MDA, 4-HNE, TBARS, that are implicated in type 2 diabetes-related complications. Abbreviations; PUFA: polyunsaturated fatty acid; ROS: reactive oxygen species; SOD: superoxide dismutase; GSH: glutathione; MDA: malondialdehyde; 4-HNE: 4-hydroxy-2-nonenal; TBARS: thiobarbituric acid reactive substances; 8-OHDG; 8-hydroxydeoxyguanosine; AGEs: advanced glycation end products.CC BY · PubMed Central

Figure 3 An overview of different antioxidants and their capacity to terminate lipid peroxidation products (especially in conditions of type 2 diabetes). Abbreviations; Cyt P450: cytochrome p450; CAT: catalase; CoQ10: Coenzyme Q10; PUFA: polyunsaturated fatty acid; ROS: reactive oxygen species; SOD: superoxide dismutase; GSH: glutathione; GSSH: oxidized glutathione; GPx: glutathione peroxidase; GR: glutathione reductase; MDA: malondialdehyde; 4-HNE: 4-hydroxy-2-nonenal; •OH: hydroxyl radical; LO•: lipid alkoxyl radical; LOO•: lipid peroxyl radical; LOOH: lipid hydroperoxides; TBARS: thiobarbituric acid reactive substances; Vit: Vitamin.CC BY · PubMed Central

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See all 102

Authors: Shabalala, S. C., Johnson, R., Basson, A. K., Ziqubu, K., Hlengwa, N., Mthembu, S. X. H., Mabhida, S. E., Mazibuko-Mbeje, S. E., Hanser, S., Cirilli, I., Tiano, L., & Dludla, P. V.
Affiliations: South African Medical Research Council (ZA)
University of Zululand (ZA)
North-West University (ZA)
University of Limpopo (ZA)
Marche Polytechnic University (IT)
Corresponding author: Shabalala, Samukelisiwe C.
Dludla, Phiwayinkosi V.
ORCID: Shabalala, Samukelisiwe C.
Johnson, Rabia
Basson, Albertus K.
Ziqubu, Khanyisani
Hlengwa, Nokulunga
Mthembu, Sinenhlanhla X. H.
Mabhida, Sihle E.
Mazibuko-Mbeje, Sithandiwe E.
Hanser, Sidney
Cirilli, Ilenia
Tiano, Luca
Dludla, Phiwayinkosi V.
Venue: Antioxidants
Publisher: MDPI AG
Published: 2022-10-20
Volume: 11
Issue: 10
Pages: 2071
ISSN: 2076-3921 (ISSN-L)
DOI: 10.3390/antiox11102071
PMC: PMC9598619
OpenAlex: W4306938593
Cited by: 102
References: 161
Citations by year: 2026: 25 · 2025: 36 · 2024: 23 · 2023: 17
FWCI: 1.68
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Antioxidants (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion, cc-by)
Funders: Biomedical Research and Innovation Platform of the South African Medical Research Council (117829 and 141929)
Topics: Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Keywords: lipid peroxidation, type 2 diabetes, malondialdehyde, 4-hydroxynonenal, oxidative stress, antioxidant enzymes, catalase, coenzyme Q10, glutathione peroxidase, superoxide dismutase, vitamin C, vitamin E, biomarkers, cardiovascular disease, glycemic control, dyslipidemia

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Detrimental Effects of Lipid Peroxidation in Type 2 Diabetes: Exploring the Neutralizing Influence of Antioxidants

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