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

Tania Gómez-Sierra,José D. Solano,María Elena Ibarra-Rubio,José Pedraza-Chaverri,Omar Noel Medina-Campos

doi:10.3390/molecules25194442

Tania Gómez-Sierra, José D. Solano + Show 3 more

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https://doi.org/10.3390/molecules25194442

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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.

Highlights

The flavonoid 4,20,40 -trihydroxichalcone, known as isoliquiritigenin (IsoLQ) (Figure 1), proceeds from the roots and rhizomes of licorice (Glycyrrizha glabra)
Not the Laboratories Cell-Porcine Kidney 1 (LLC-PK1) cells wereconcentrations treated with CPhigher
Hormesis is more than a dose-response relationship, it is a quantitative and temporal manifestation of reparative processes that is adaptive in nature, such as unfolded protein response (UPR) elicited by endoplasmic reticulum (ER) stress [42,43,46,47,50,60,61]

Summary

Introduction

The flavonoid 4,20 ,40 -trihydroxichalcone, known as isoliquiritigenin (IsoLQ) (Figure 1), proceeds from the roots and rhizomes of licorice (Glycyrrizha glabra). It is used in Asia as an herbal medicine due to its anti-inflammatory, antimicrobial, antitumoral, and antioxidant properties [1,2,3,4,5,6,7,8]. Cisplatin or cis-diaminodichloroplatin II (CP), is an antineoplastic drug. On the hand,States cisplatin or Drug cis-diaminodichloroplatin. II (CP), anthe antineoplastic drug approved by other the United Federal. Administration since 1978 usedisfor treatment of many approved by the United States Drug IsoLQ has been used as an endoplasmic reticulum (ER) stress inducer in cancer cell lines to induce apoptosis [8,10,11,12,13,14,15,16] and has cytoprotective effects in non-cancer cells, such as liver and kidney cells [1,4,9,16,17,18].

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