Gastric diseases represent a significant global public health challenge, characterized by molecular dysregulation in redox homeostasis and heightened oxidative stress. Although prior preclinical studies have demonstrated the cytoprotective antioxidant effects of alginate oligosaccharides (AOSs) through the Nrf2 pathway, whether such mechanisms apply to gastric diseases remains unclear. In this study, we used the GES-1 gastric cell line exposed to hydrogen peroxide (H₂O₂) as a damage model to investigate the impact of AOS on cell viability and its associated mechanisms. Our results revealed that pre-incubation with AOS for either 4 h or 24 h significantly improved the viability of GES-1 cells exposed to H₂O₂. In addition, AOS reduced the intracellular ROS levels, activating the Nrf2 signaling pathway, with increased Nrf2 protein and mRNA expression and a significant upregulation of the target genes HO-1 and NQO1. The activation of Nrf2 was correlated with decreased Keap1 protein expression and an increased level of the autophagy protein p62/SQSTM1, suggesting the activation of Nrf2 through a noncanonical pathway. This study suggests that AOS is a potential treatment for protecting gastric epithelial cells from oxidative stress by activating the p62/SQSTM1-Keap1-Nrf2 axis and laying the foundation for future investigations about its specific therapeutic mechanisms.

Dysregulation of zinc and zinc transporters families has been associated with the genesis and progression of prostate cancer. The prostate epithelium utilizes two types of zinc transporters, the ZIP (Zrt-, Irt-related Protein) and the ZnTs (Zinc Transporter), to transport zinc from the blood plasma to the gland lumen. ZIP transporters uptake zinc from extracellular space and organelle lumen, while ZnT transporters release zinc outside the cells or to organelle lumen. In prostate cancer, a commonly observed low zinc concentration in prostate tissue has been correlated with downregulations of certain ZIPs (e.g., ZIP1, ZIP2, ZIP3, ZIP14) and upregulations of specific ZnTs (e.g., ZnT1, ZnT9, ZnT10). These alterations may enable cancer cells to adapt to toxic high zinc levels. While zinc supplementation has been suggested as a potential therapy for this type of cancer, studies have yielded inconsistent results because some trials have indicated that zinc supplementation could exacerbate cancer risk. The reason for this discrepancy remains unclear, but given the high molecular and genetic variability present in prostate tumors, it is plausible that some zinc transporters—comprising 14 ZIP and 10 ZnT members—could be dysregulated in others patterns that promote cancer. From this perspective, this review highlights novel dysregulation, such as ZIP-Up/ZnT-Down, observed in prostate cancer cell lines for ZIP4, ZIP8, ZnT2, ZnT4, ZnT5, etc. Additionally, an in silico analysis of an available microarray from mouse models of prostate cancer (Nkx3.1;Pten) predicts similar dysregulation pattern for ZIP4, ZIP8, and ZnT2, which appear in early stages of prostate cancer progression. Furthermore, similar dysregulation patterns are supported by an in silico analysis of RNA-seq data from human cancer tumors available in cBioPortal. We discuss how these dysregulations of zinc transporters could impact zinc supplementation trials, particularly focusing on how the ZIP-Up/ZnT-Down dysregulation through various mechanisms might promote prostate cancer progression.

Background/Objectives: Oxidative stress is a key pathogenic factor in gastric diseases (GDs). Nutraceuticals with antioxidant activity derived from macroalgae represent promising preventive strategies. However, Chilean macroalgae remains poorly explored in the context of GDs, particularly associated with oxidative stress. This study evaluated the antioxidant and cytoprotective properties of crude aqueous and ethanolic extracts from green, brown, and red macroalgae collected along the north-central coast of Chile. Methods: Crude extracts were prepared from green, brown, and red macroalgae and evaluated for antioxidant activity via ABTS, DPPH, and FRAP assays. Using hydrogen peroxide-induced oxidative stress in GES-1 gastric epithelial cells, we assessed cell viability (MTS assay), intracellular reactive oxygen species (ROS) levels (time-lapse confocal microscopy), and apoptosis (active caspase-3 detection). Results: All extracts exhibited antioxidant activity; the red macroalgae Gracilaria chilensis displayed the highest flavonoid content (up to 2.236 mg QE/g dw). Notably, extracts from G. chilensis, S. gaudichaudii, and M. canaliculata preserved GES-1 cell viability under hydrogen peroxide-induced stress, outperforming green and brown species, demonstrating the superior cytoprotective capacity of red macroalgae compared to other groups. Furthermore, G. chilensis extracts significantly reduced intracellular ROS levels and attenuated ROS-induced apoptosis. Conclusions: Red macroalgae extracts, particularly G. chilensis, exhibit strong antioxidant and cytoprotective effects. Our findings demonstrate that these species outperform green and brown macroalgae, addressing a gap in knowledge regarding Chilean marine resources. These results support their potential development as nutraceuticals for the prevention of oxidative stress-related gastric diseases and highlight red macroalgae as a valuable source of bioactive compounds for diet-based preventive strategies.

Background/Objectives: Oxidative stress is a key pathogenic factor in gastric diseases (GDs). Nutraceuticals with antioxidant activity derived from macroalgae represent promising preventive strategies. However, Chilean macroalgae remains poorly explored in the context of GDs, particularly associated with oxidative stress. This study evaluated the antioxidant and cytoprotective properties of crude aqueous and ethanolic extracts from green, brown, and red macroalgae collected along the north–central coast of Chile. Methods: Crude extracts were prepared from green, brown, and red macroalgae and evaluated for antioxidant activity via ABTS, DPPH, and FRAP assays. Using hydrogen peroxide-induced oxidative stress in GES-1 gastric epithelial cells, we assessed cell viability (MTS assay), intracellular reactive oxygen species (ROS) levels (time-lapse confocal microscopy), and apoptosis (active caspase-3 detection). Results: All extracts exhibited antioxidant activity; the red macroalgae Gracilaria chilensis displayed the highest flavonoid content (up to 2.24 mg QE/g dw). Notably, extracts from G. chilensis, S. gaudichaudii, and M. canaliculata preserved GES-1 cell viability under hydrogen peroxide-induced stress, outperforming green and brown species, demonstrating the superior cytoprotective capacity of red macroalgae compared to other groups. Furthermore, G. chilensis extracts significantly reduced intracellular ROS levels and attenuated ROS-induced apoptosis. Conclusions: Red macroalgae extracts, particularly G. chilensis, exhibit strong antioxidant and cytoprotective effects. Our findings demonstrate that these species outperform green and brown macroalgae, addressing a gap in knowledge regarding Chilean marine resources. These results support their potential development as nutraceuticals for the prevention of oxidative stress-related gastric diseases and highlight red macroalgae as a valuable source of bioactive compounds for diet-based preventive strategies.