The Protective Effect of Chlorella vulgaris Supplement Against Mercury Exposure Is Associated with DMT1: A Transcriptomic Analysis

Daily supplements have emerged as a compelling strategy for heavy metal detoxification (e.g., Hg and Pb), given that conventional chelation therapy lacks chronic exposure data and is heavily reliant on the doctor’s experience. Among such natural agents, Chlorella vulgaris (C. vulgaris), a commercially available supplement, is known for its notable heavy metal-binding capacity and ancillary benefits. Yet, the detoxification mechanisms of action of C. vulgaris have remained largely unexplored. In this study, our transcriptomic and signaling analyses demonstrated that the chemically characterized aqueous extract of C. vulgaris may have attenuated Hg2+-induced mitotic catastrophe in HEK-293 cells and was predicted to activate AKT signaling and modulate the expression of zinc finger protein-related genes. Furthermore, in corresponding DMT1-overexpressing cells, the protective effects of the extract were associated with the modulation of translation and ubiquitination pathways. These changes may coincide with the partial recovery of the two major ribosomal stress surveillance pathways. Intriguingly, under conditions in which Hg2+ did not provoke the more severe ribotoxic stress response, the C. vulgaris extract appeared to alleviate Hg2+-induced ribosomal stress by engaging both ribosomal quality control and the integrated stress response, particularly the response of GCN2 to amino acid deficiency. Ultimately, these findings suggest the protective effect of C. vulgaris extract against Hg2+ toxicity is associated with DMT1 at the transcriptome level, warranting further experimental investigation of its potential as a nutraceutical adjuvant in mercury detoxification.