Enhanced Efficacy of HUVEC Treatment with NLC - Astaxanthin at Oxidative Stress Situation: A Novel Nanomedicine Approach

Introduction: Oxidative stress arises from an imbalance between reactive oxygen species (ROS) production and the body's antioxidant defenses, leading to cellular damage and contributing to various diseases, including cardiovascular diseases, cancer, and diabetes. Key genes such as Nrf۲, HO-۱, and NQO۱ play vital roles in regulating antioxidant responses. Astaxanthin, a potent antioxidant found in certain algae and seafood, has shown promise in mitigating oxidative stress; however, its hydrophobic nature limits its bioavailability. This study explores the use of nanostructured lipid carriers (NLCs) to enhance the delivery of astaxanthin and assess its protective effects against oxidative stress induced by antimycin A (AMA) and ۲,۲'-azobis(۲-amidinopropane) dihydrochloride (AAPH). Methods: HUVEC cells were treated with varying concentrations of NLCs containing astaxanthin (NLC-A) under oxidative stress conditions induced by AMA and AAPH. The optimal concentration of NLC-A was determined through MTT assays, followed by evaluation of gene expression related to oxidative stress and apoptosis pathways, including Nrf۲, HO-۱, NQO۱, Bcl-۲, mTOR, and Caspase-۳. Results: The study identified ۷ µM as the optimal concentration of NLC-A for HUVEC cells. Treatment with NLC-A significantly upregulated the expression of Nrf۲, leading to increased levels of HO-۱ and NQO۱, which are essential for detoxifying ROS. Additionally, NLC-A treatment elevated Bcl-۲ expression, providing protection against apoptosis, while simultaneously downregulating Caspase-۳/mTOR activation. Conclusion: The findings highlight the dual role of Nrf۲ in enhancing cellular antioxidant defenses and promoting cell survival under oxidative stress. The upregulation of Bcl-۲ and the inhibition of Caspase-۳ suggest that NLC-A not only mitigates oxidative damage but also regulates apoptotic signaling pathways, thereby reducing cell death. This study underscores the potential of NLCs as effective delivery systems for astaxanthin, offering a promising strategy for managing oxidative stress-related diseases.

کلیدواژه ها:

Oxidative Stress ، NLC ، Astaxanthin ، HUVEC