EGCG alleviates Ochratoxin A-induced pyroptosis in rat's kidney by inhibiting NLRP3/Caspase-1/GSDMD signaling pathway

• Published in: Food and chemical toxicology Vol. 193; p. 115006
• Main Authors: Bozkurt, Ilyas, Halici, Zekai, Bahador Zirh, Elham, Palabiyik-Yucelik, Saziye Sezin
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-11-2024
• Subjects: Epigallocatechin gallate; GSDMD; NLRP3; Ochratoxin A; Pyroptosis; GSDMD; NLRP3; Epigallocatechin gallate; Pyroptosis; Ochratoxin A; pyroptosis; ochratoxin A
• ISSN: 0278-6915; 1873-6351; 1873-6351
• DOI: 10.1016/j.fct.2024.115006

Ochratoxin A (OTA) exposure is inevitable due to its contamination in foods, and there is no treatment for the OTA induced organ toxicity. We evaluate the effect of epigallocatechin gallate (EGCG) on the nephrotoxicity caused by OTA, and to reveal the relationship of this effect with the NLRP3/Caspase-1/GSDMD pathway dependent pyroptosis. 40 male Wistar albino rats divided into 5 groups (n = 8, per group) 0.5 mg/kg/day OTA were administered to the rats and 50 mg/kg and 100 mg/kg EGCG were administered to the groups by gavage orally for 14 days. Serum urea and creatinine levels increased significantly with OTA exposure. Similarly, it was determined that significant changes in oxidative stress parameters with OTA exposure in kidney tissue. Also, there was a significant increase in kidney tissue TGF-β, NF-κB, IL-1β, IL-18, NLRP3, Caspase-1 and GSDMD mRNA expressions with OTA exposure. EGCG administration augmented a dose-dependent decrease in the aforementioned parameters. NLRP3/Caspase-1/GSDMD pathway is induced in the kidneys due to OTA exposure were shown with this study. Potent antioxidant EGCG could alleviate the pathways specified with this study in OTA nephrotoxicity and its supplementation may be effective strategies for the protection.
•Gasdermin-D (GSDMD) mediated pyroptosis through NLRP3 activation exacerbates the toxicity of OTA•OTA treatment elevated expression of pro-inflammatory cytokines•EGCG could protect neprotoxicity induced by OTA exposure•OTA induced pyroptosis alleviated by EGCG inhibiting NLRP3/Caspase-1/GSDMD pathway