Targeting Endoplasmic Reticulum Stress by Natural and Chemical Compounds Ameliorates Cisplatin-Induced Nephrotoxicity: A Review.

Abstract

Cisplatin is a chemotherapeutic that dose-dependently causes renal complications such as decreased kidney function and acute kidney injury. The endoplasmic reticulum (ER) is responsible for calcium homeostasis and protein folding and plays a major part in cisplatin's nephrotoxicity. The current article reviews how chemical and natural compounds modulate cisplatin-induced apoptosis, autophagy, and inflammation by inhibiting ER stress signaling pathways. The available evidence indicates that natural compounds (Achyranthes aspera water-soluble extract, morin hydrate, fucoidan, isoliquiritigenin, leonurine, epigallocatechin-3-gallate, grape seed proanthocyanidin, and ginseng polysaccharide) and chemicals (Sal003, NSC228155, TUG891, dorsomorphin (compound C), HC-030031, dexmedetomidine, and recombinant human erythropoietin (rHuEpo)) can alleviate cisplatin nephrotoxicity by suppression of ER stress signaling pathways including IRE1α/ASK1/JNK, PERK-eIF2α-ATF4, and ATF6, as well as PI3K/AKT signaling pathway. Since ER and related signaling pathways are important in cisplatin nephrotoxicity, agents that can inhibit the abovementioned signaling pathways may hold promise in alleviating this untoward adverse effect.