Exploring the Mechanisms of Iron Overload-Induced Liver Injury in Rats Based on Transcriptomics and Proteomics.

Iron is a trace element that is indispensable for the growth and development of animals. Excessive iron supplementation may lead to iron overload and elevated reactive oxygen species (ROS) production in animals, causing cellular damage. Nevertheless, the precise mechanism by which iron overload causes cell injury remains to be fully elucidated. In this study, 16 male SD rats aged 6 to 7 weeks were randomly assigned to either a control group (CON) or an iron overload group (IO). Rats in the iron overload group received 150 mg/kg iron dextran injections every three days for a duration of four weeks. The results indicated that iron treatment with iron dextran significantly increased the scores of steatosis ( < 0.05) and inflammation ( < 0.05) in the NAS score. The integrated transcriptomic and proteomic analysis suggests that HO-1 and Lnc286.2 are potentially significant in iron overload-induced liver injury in rats. In vitro experiments utilizing ferric ammonium citrate (FAC) were conducted to establish an iron overload model in rat liver-derived BRL-3A cells. The result found that FAC treatment can significantly increase the BRL-3A cell's Fe content ( < 0.05), ROS < 0.01), lipid ROS ( < 0.01) levels, and the expression of the HO-1 gene and protein ( < 0.01), aligning with proteomic and transcriptomic findings. HO-1 inhibition can significantly decrease BRL-3A cell vitality ( < 0.01) and promote ROS ( < 0.05) and lipid ROS ( < 0.01), thus aggravating FAC-induced BRL-3A cell iron overload damage. Using the agonist of HO-1 agonist cobalt protoporphyrin (CoPP) to induce HO-1 overexpression can significantly alleviate the decrease in FAC-induced BRL-3A cell viability ( < 0.01), ROS ( < 0.01), and lipid ROS ( < 0.01). In addition, siLnc286.2 treatment can increase HO-1 expression, alleviate the decline of FAC-induced BRL-3A cell activity, and increase lipid ROS ( < 0.05) content. In conclusion, the findings of this study suggest that by suppressing the expression of Lnc286.2, we can enhance the expression of HO-1, which in turn alleviates lipid peroxidation in cells and increases their antioxidant capacity, thereby exerting a protective effect against liver cell injury induced by iron overload.