Dysregulation of ferroptosis may participate in the mitigating effect of CoCl2 on contrast-induced nephropathy

Abstract

Background

Contrast agents can directly or indirectly induce renal tubular ischemia and hypoxic damage. Given that cobalt chloride (CoCl₂) can protect renal tubules, the protective effect and potential mechanism of action of CoCl₂ on contrast-induced nephropathy (CIN) warrant investigation.

Methods

A CIN mouse model was established to determine the protective effect of CoCl₂ on renal injury in vivo. Then, TMT-based proteomics was performed to determine the differentially expressed proteins (DEPs), following which, enrichment analyses of gene ontology and the KEGG pathway were performed. In vitro, a CIN model was constructed with renal tubular epithelial cells (HK-2) to determine the effect of CoCl₂ on potential targets and the role of the key protein identified from the in vivo experiments.

Results

CoCl₂ treatment decreased the levels of BUN and serum creatinine (sCr), while increasing the levels of urea and creatinine (Cr) in the urine of mice after CIN injury. Damage to the renal tubules in the CoCl₂ treatment group was significantly less than in the CIN model group. We identified 79 DEPs after treating the in vivo model with CoCl₂, and frequently observed ferroptosis-related GO and KEGG pathway terms. Of these, Hp (haptoglobin) was selected and found to have a strong renoprotective effect, even though its expression level in kidney tissue decreased after CoCl₂ treatment. In HK-2 cells, overexpression of Hp reduced the ferroptosis caused by erastin, while knocking down Hp negated the attenuation effect of CoCl₂ on HK-2 cell ferroptosis.

Conclusion

CoCl₂ attenuated kidney damage in the CIN model, and this effect was associated with the decrease in ferroptosis mediated by Hp.