Astaxanthin Inhibits Autophagic Cell Death Induced by Bisphenol A in Human Dermal Fibroblasts

Abstract

Astaxanthin, a natural antioxidant carotenoid, is a nutrient with diverse health benefits, given that it decreases the risk of oxidative stress-related diseases. In the present study, we investigate the functional role of astaxanthin during autophagic cell death induced by the estrogenic endocrine-disrupting chemical bisphenol A (BPA) in normal human dermal fibroblasts (NHDF). BPA significantly induced apoptotic cell death and autophagy in NHDF. Autophagic cell death evoked by BPA was significantly restored upon a treatment with astaxanthin (10 μM) via the inhibition of intracellular reactive oxygen species (ROS) production. Astaxanthin inhibited the phosphorylation of extracellular signal-regulated kinases (ERK) stimulated by ROS production, but it did not influence the activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in BPA-treated NHDF. Astaxanthin abrogated the ERK-mediated activation of nuclear factor-kappa B (NF-κB), which is responsible for the mRNA expression of LC3-II, Beclin-1, Atg12, and Atg14 during apoptotic cell death induced by BPA. These results indicate that astaxanthin is a pharmacological and nutritional agent that blocks the skin fibroblastic autophagic cell death induced by BPA in human dermal fibroblasts.

A 3D-Printed Wound-Healing Material Composed of Alginate Dialdehyde–Gelatin Incorporating Astaxanthin and Borate Bioactive Glass Microparticles

“…This can be attributed to its preventive role against the MMP expression in fibroblasts and its supportive action toward the expression of different biomarkers playing a role in wound healing [e.g., basic fibroblast growth factor (bFGF)] . Additionally, ASX can scavenge excessive intracellular reactive oxygen species (ROS) and reduce oxidative stress, thereby preventing dermal cellular damage by blocking apoptotic and autophagic pathways . On the other hand, in fibroblasts, ROS are known as signaling molecules that can trigger particular cell functions including cell differentiation, proliferation, death, and senescence and release of cytokines .…”

“…48 Additionally, ASX can scavenge excessive intracellular reactive oxygen species (ROS) and reduce oxidative stress, thereby preventing dermal cellular damage by blocking apoptotic and autophagic pathways. 49 On the other hand, in fibroblasts, ROS are known as signaling molecules that can trigger particular cell functions including cell differentiation, proliferation, death, and senescence and release of cytokines. 50 Therefore, fibroblast proliferation is assumed to be properly regulated by the presence of ASX.…”

“…62 As mentioned earlier, ASX can scavenge excessive intracellular ROS and reduce oxidative stress. 49 As a proven fact, the increased levels of ROS lead to oxidation of membrane phospholipids, DNA, and proteins 63 and induce vascular dysfunction. 64 The ROS production level is key to determining the resulting response.…”

Haematococcus pluvialis as a Potential Source of Astaxanthin with Diverse Applications in Industrial Sectors: Current Research and Future Directions

“…Furthermore, Chalyk et al (2017) [52] observed that the levels of malondialdehyde (MDA), a recognised indicator of systemic oxidative stress, were reduced after a human model received 4 mg daily doses of astaxanthin (by 11.2% on day 15 and by 21.7% on day 29). Furthermore, Seong-Ryeong et al, (2021) [54] revealed astaxanthin as a nutritional supplement that prevents the skin fibroblastic autophagic cell death generated by bisphenol A (BPA) in normal human dermal fibroblasts (NHDF), as well as reduced the phosphorylation of extracellular signal-regulated kinases (ERK) driven by ROS generation. In NHDF, BPA dramatically increased apoptotic cell death and autophagy.…”

The Protective Effect of Carotenoids, Polyphenols, and Estradiol on Dermal Fibroblasts under Oxidative Stress

“…This modulation includes reduction in the activities of the nuclear factor-κB (NF-κB) transcription system, activator protein 1 (AP-1), and mitogen-activated protein kinase (MAPK) [ 17 , 18 ], and improving the antioxidant defense mechanism [ 19 ]. Several studies, including our own, suggest that modulation of these signaling pathways by phytonutrients can lead to a reduction in inflammatory processes [ 20 , 21 , 22 ] and MMP expression [ 17 , 23 ], and increase collagen synthesis [ 17 ].…”