Sulforaphane Exposure Prevents Cadmium-Induced Toxicity and Mitochondrial Dysfunction in the Nematode <i>Caenorhabditis elegans</i> by Regulating the Insulin/Insulin-like Growth Factor Signaling (IIS) Pathway

Abstract

Cadmium (Cd) is a heavy metal that is highly toxic to humans and animals. Its adverse effects have been widely associated with mitochondrial alterations. However, there are not many treatments that target mitochondria. This study aimed to evaluate the impact of sulforaphane (SFN) pre-exposure against cadmium chloride (CdCl2)-induced toxicity and mitochondrial alterations in the nematode Caenorhabditis elegans (C. elegans), by exploring the role of the insulin/insulin-like growth factor signaling pathway (IIS). The results revealed that prior exposure to SFN protected against CdCl2-induced mortality and increased lifespan, body length, and mobility while reducing lipofuscin levels. Furthermore, SFN prevented mitochondrial alterations by increasing mitochondrial membrane potential (Δψm) and restoring mitochondrial oxygen consumption rate, thereby decreasing mitochondrial reactive oxygen species (ROS) production. The improvement in mitochondrial function was associated with increased mitochondrial mass and the involvement of the daf-16 and skn-1c genes of the IIS signaling pathway. In conclusion, exposure to SFN before exposure to CdCl2 mitigates toxic effects and mitochondrial alterations, possibly by increasing mitochondrial mass, which may be related to the regulation of the IIS pathway. These discoveries open new possibilities for developing therapies to reduce the damage caused by Cd toxicity and oxidative stress in biological systems, highlighting antioxidants with mitochondrial action as promising tools.

Keywords

• <i>Caenorhabditis elegans</i>
• sulforaphane
• cadmium toxicity
• mitochondrial
• oxidative stress