Imperatorin ameliorates renal damage and modulates MAPK, Nrf2, and NF-kB pathways in mercury-chloride-exposed rats: A toxicological study relevant to skin lightening practices.

BACKGROUND

A major global public health concern is the widespread and illegal use of mercury compounds in skin-lightening cosmetics, mainly because of their extreme systemic toxicity, especially to the kidneys. Imperatorin is a promising natural furanocoumarin compound with high antioxidant properties. This study investigates the mechanism of mercury-induced nephrotoxicity and the curative properties of imperatorin, focusing on the NF-κB, MAPKs, and Nrf2 signalling pathways.

METHODS

Rats were divided into control, mercury-chloride (HgCl2)-treated (2.5 mg/kg), imperatorin-treated (15 mg/kg), and two co-treated groups receiving HgCl2 (2.5 mg/kg) with either 10 mg/kg or 15 mg/kg of imperatorin. Our study examined tissue histopathology, renal function markers, oxidative stress parameters, inflammatory cytokines, as well as the expression of nephrin, podocin, Kidney Injury Marker-1 (KIM-1), Nrf2, NF-kB, p38, ERK, and JNK mRNA levels. Further, the activated protein levels of p38, ERK and JNK were confirmed using a western blot.

RESULTS

Imperatorin decreased the levels of creatinine, urea, and uric acid; increased protein and albumin levels and restored pathological changes in a dose-dependent manner. The antioxidant levels of superoxide dismutase, reduced glutathione, glutathione peroxidase and catalase were also restored by imperatorin treatment while modulating the levels of ROS, MDA, TNF-α, IL-6 and IL-1β. Gene expression analysis showed a significant increase in KIM-1 and a decrease in nephrin and podocin levels in the HgCl2 group, suggesting kidney injury. Imperatorin modulated the gene expression levels of MAPKs (p38, Erk, and Jnk), Nrf2, and NF-κB in the HgCl2 groups. Protein expression levels of MAPKs confirmed that MAPK signal activation in the HgCl2 group decreased by imperatorin treatment.

CONCLUSION

These results show that in an in vivo model, imperatorin provides significant protection against HgCl2-induced nephrotoxicity.