Pseudohypoxia induced by chemical pollutants: Biochemical evidence of environmental vulnerability

Chemical pollutants can abnormally elevate hypoxia-inducible factor 1-alpha (HIF-1α) levels under normoxic conditions, leading to pseudohypoxia. This condition disrupts normal cellular energy metabolism, gene expression, and signal transduction, thereby inducing detrimental physiological effects. Pseudohypoxia can also increase the risk of various diseases, including cancer, cardiovascular diseases, and chronic respiratory diseases, while adversely affecting disease treatment and prognosis. Focusing on the intersection between environmental pollution and hypoxia signaling pathways, this review proposes a novel concept that chemical pollutants can induce pseudohypoxia and elucidates its underlying mechanisms. We also identify various environmental pollutants that induce pseudohypoxia, including but not limited to metals and metalloids (e.g., cadmium, cobalt, arsenic), persistent organic pollutants (e.g., BPA, dioxins, PCBs), and atmospheric particulate pollutants (e.g., PM2.5, diesel exhaust particles), and examine the complex interplay between these pollutants, pseudohypoxia, and various diseases. This review aims to offer novel strategies for managing pseudohypoxia caused by environmental exposures, thereby offering new insights into the prevention and treatment of environmental exposure-related disease and susceptibility.