Isoliquiritigenin Pretreatment Induces Endoplasmic Reticulum Stress-Mediated Hormesis and Attenuates Cisplatin-Induced Oxidative Stress and Damage in LLC-PK1 Cells

Abstract

Isoliquiritigenin (IsoLQ) is a flavonoid with antioxidant properties and inducer of endoplasmic reticulum (ER) stress. In vitro and in vivo studies show that ER stress-mediated hormesis is cytoprotective; therefore, natural antioxidants and ER stress inducers have been used to prevent renal injury. Oxidative stress and ER stress are some of the mechanisms of damage involved in cisplatin (CP)-induced nephrotoxicity. This study aims to explore whether IsoLQ pretreatment induces ER stress and produces hormesis to protect against CP-induced nephrotoxicity in Lilly Laboratories Cell-Porcine Kidney 1 (LLC-PK1) cells. During the first stage of this study, both IsoLQ protective concentration and pretreatment time against CP-induced toxicity were determined by cell viability. At the second stage, the effect of IsoLQ pretreatment on cell viability, ER stress, and oxidative stress were evaluated. IsoLQ pretreatment in CP-treated cells induces expression of glucose-related proteins 78 and 94 kDa (GRP78 and GRP94, respectively), attenuates CP-induced cell death, decreases reactive oxygen species (ROS) production, and prevents the decrease in glutathione/glutathione disulfide (GSH/GSSG) ratio, free thiols levels, and glutathione reductase (GR) activity. These data suggest that IsoLQ pretreatment has a moderately protective effect on CP-induced toxicity in LLC-PK1 cells, through ER stress-mediated hormesis, as well as by the antioxidant properties of IsoLQ.

Administration of isoliquiritigenin prevents nonalcoholic fatty liver disease through a novel IQGAP2‐CREB‐SIRT1 axis

“…Based on the above findings and ISO has been reported to improve oxidative stress (Alzahrani et al, 2020;G omez-Sierra, Medina-Campos, Solano, Ibarra-Rubio, & Pedraza-Chaverri, 2020) Consistent with these data, mice treated with ISO also displayed elevated expression of fatty acid oxidation-related proteins but reduced expression of proteins related to lipid synthesis (Figure 3F-H, Data S1). Taken together, these data demonstrate that ISO reduced intracellular lipid content by reducing lipid synthesis and increasing lipid oxidation processes.…”

“…Based on the above findings and ISO has been reported to improve oxidative stress (Alzahrani et al, 2020; Gómez‐Sierra, Medina‐Campos, Solano, Ibarra‐Rubio, & Pedraza‐Chaverri, 2020), we next explored how ISO lowered lipid content in hepatocytes. First, we measured mitochondrial function using the Seahorse XF Cell Mito Stress Test kit.…”

Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications

“…Isoliquiritigenin (IsoLQ) is a flavonoid with antioxidant properties and is an inducer of ER stress. It was shown that IsoLQ pretreatment of a kidney cell line induced ER stress-mediated hormesis [ 60 ]. Other agents inducing a hormetic dose response are chloroquine [ 61 ] and green tea with its principal constituent (-)-epigallocatechin-3-gallate (EGCG) [ 62 ].…”

Protective Effects of 6-Shogaol, an Active Compound of Ginger, in a Murine Model of Cisplatin-Induced Acute Kidney Injury

“…In addition, cisplatin treatment decreased the GSH/GSSG ratio, which was significantly reversed by 6-shogaol. A decrease in the GSH/GSSG ratio indicates increased oxidative stress [ 39 , 40 ]. Altogether, our data indicates that 6-shogaol exhibited an anti-oxidative effect in cisplatin-induced AKI.…”