Multiple-species hormetic phenomena induced by indole: A case study on the toxicity of indole to bacteria, algae and human cells.

Hormesis is a dose-response relationship phenomenon characterized by low-dose stimulation and high-dose inhibition. Although hormetic phenomena have been reported in broadly ranging biological areas, there is still no unified mechanism of hormesis. Investigating multiple-species hormesis of one compound and then exploring the possible mechanism may be an effective approach to clarify the reason for the occurrence of hormetic phenomena in a broad range of organisms. In this study, indole was selected as the test chemical due to the broad biological and hormetic effects of indole compounds. The results show that indole induces multiple-species hormetic phenomena in bacteria (Aliivibrio fischeri (A. fischeri), Escherichia coli and Bacillus subtilis), algae (Microcystis aeruginosa and Selenastrum capricornutum), and human cells (human skin fibroblasts and human cervical cancer cells). Through in-depth investigation of the time-dependent hormetic effects of indole, indole derivatives and indole's structural analogs on the bioluminescence of A. fischeri, indole ring has been identified as the potential key structure that causes indole to act on quorum sensing of A. fischeri to induce hormetic effects on the bioluminescence at lag, logarithmic, and stationary phases. Therefore, the occurrence of multiple-species hormetic phenomena is speculated to be derived from the action of indole on the cell-to-cell communication of organism cells. This paper can not only further confirm the generalizability of hormesis but also provide a reasonable explanation for hormesis, which will benefit the development of hormesis and the risk assessment of environmental pollutants.