Antioxidant-enzyme interactions and their role in non-communicable diseases

Introduction

Oxidative stress, caused by an imbalance between reactive oxygen species (ROS) and antioxidant defenses, plays a central role in the development of non-communicable diseases (NCDs). These diseases, including cardiovascular disorders, diabetes, neurodegenerative conditions, cancer, and liver and kidney diseases, are among the leading causes of morbidity and mortality worldwide. Enzymatic and non-enzymatic antioxidants serve as the body's primary defense against ROS, maintaining redox homeostasis and preventing cellular damage. However, when ROS levels exceed the capacity of antioxidant defenses, oxidative stress ensues, contributing to disease pathogenesis. This review explores the mechanisms by which antioxidant-enzyme interactions regulate oxidative stress and their implications for managing NCDs.

Mechanisms of antioxidant-enzyme interaction

Antioxidants mitigate oxidative damage through enzymatic and non-enzymatic pathways. Non-enzymatic antioxidants such as vitamin C, vitamin E, carotenoids, flavonoids, and polyphenols directly scavenge ROS or regenerate oxidized enzymatic antioxidants. Enzymatic antioxidants-including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GRd), and thioredoxin reductase-play crucial roles in neutralizing ROS.

The interplay between antioxidants and enzymes enhances the efficacy of the antioxidant defense system. For example, vitamin C regenerates vitamin E, while melatonin upregulates GPx and SOD activity, reducing oxidative stress. Similarly, flavonoids and polyphenols modulate the expression of antioxidant enzymes, exerting anti-inflammatory and cytoprotective effects.

Antioxidant-enzyme interactions in disease pathogenesis

Oxidative stress contributes to various NCDs through mechanisms such as lipid peroxidation, protein oxidation, DNA damage, and inflammatory signaling. The review highlights key interactions in different diseases:

• Cardiovascular diseases (CVDs): Antioxidants such as flavonoids, vitamin C, and vitamin E enhance the activity of SOD, CAT, and GPx, reducing ROS-induced vascular damage. Polyphenols inhibit lipid peroxidation and inflammation, lowering the risk of atherosclerosis and hypertension.
• Neurodegenerative diseases (Alzheimer's and Parkinson's disease): Antioxidants like resveratrol, Coenzyme Q10 (CoQ10), and carotenoids improve neuronal survival by enhancing antioxidant enzyme activity. SOD and GPx protect neurons from oxidative damage, while vitamin E reduces peroxyl radicals implicated in neurodegeneration.
• Cancer: Tumor cells exploit antioxidant pathways to survive under oxidative stress. While antioxidants can protect normal cells from ROS-induced DNA damage, excessive antioxidant enzyme activity in tumors may promote survival and resistance to therapy. Targeting SOD and GPx in cancer cells could enhance chemotherapy sensitivity.
• Diabetes: Oxidative stress impairs insulin signaling and contributes to complications such as diabetic neuropathy and nephropathy. Polyphenols and flavonoids enhance the activity of SOD and CAT, improving glucose metabolism and reducing oxidative damage.
• Liver and kidney diseases: Hepatic and renal oxidative stress leads to inflammation and fibrosis. Antioxidant therapy, including vitamins C and E, flavonoids, and polyphenols, supports enzymatic antioxidant activity, mitigating disease progression.

Therapeutic strategies targeting antioxidant-enzyme interactions

Emerging therapeutic strategies harness antioxidant-enzyme interactions to manage NCDs. Key approaches include:

• Dietary antioxidants: Consuming polyphenol-rich foods, flavonoids, and vitamins C and E enhances antioxidant enzyme function.
• Pharmacological agents: Drugs that activate Nrf2, a key regulator of antioxidant responses, show promise in reducing oxidative stress-related damage.
• Gene therapy: Modulating the expression of antioxidant enzymes could provide targeted interventions for diseases like cancer and neurodegeneration.

Future perspectives and conclusion

Understanding the intricate interactions between antioxidants and enzymes is essential for developing effective therapeutic strategies for NCDs. While dietary and pharmacological interventions offer potential benefits, further research is needed to optimize antioxidant therapy. Future studies should focus on elucidating the molecular mechanisms of antioxidant-enzyme regulation, identifying novel therapeutic targets, and developing precision medicine approaches tailored to individual oxidative stress profiles.

By advancing our knowledge of antioxidant-enzyme interactions, we can improve the prevention and treatment of NCDs, ultimately reducing their global burden.

Ezema, B. O., et al. (2024). Antioxidant-enzyme Interaction in Non-communicable Diseases. Journal of Exploratory Research in Pharmacology. doi.org/10.14218/jerp.2024.00020.