6-Paradol alleviates Diclofenac-induced acute kidney injury via autophagy enhancement-mediated by AMPK/AKT/mTOR and NLRP3 inflammasome pathways.

Autor: El-Maadawy WH; Department of Pharmacology, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt. Electronic address: w.elmadawy@tbri.gov.eg., Hassan M; Department of Immunology, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt., Abdou RM; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt., El-Dine RS; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt. Electronic address: riham.salaheldine@pharma.cu.edu.eg., Aboushousha T; Department of Pathology, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt., El-Tanbouly ND; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt., El-Sayed AM; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt.
Jazyk: angličtina
Zdroj: Environmental toxicology and pharmacology [Environ Toxicol Pharmacol] 2022 Apr; Vol. 91, pp. 103817. Date of Electronic Publication: 2022 Jan 25.
DOI: 10.1016/j.etap.2022.103817
Abstrakt: Diclofenac (DIC)-induced acute kidney injury (AKI) causes high morbidity and mortality. With the absence of satisfactory treatment, we investigated the protective effects of 6-Paradol (PDL) against DIC-induced AKI, with focus on renal autophagy and NLRP3 inflammasome pathways . PDL has anti-inflammatory, antioxidant and AMPK-activation properties. PDL was administered to DIC-challenged rats. Nephrotoxicity, oxidative stress, inflammatory, and autophagy markers and histopathological examinations were evaluated. Compared to DIC, PDL restored serum nephrotoxicity, renal oxidative stress and pro-inflammatory markers. PDL almost restored renal architecture, upregulated renal Nrf2 pathway via enhancing Nrf2 mRNA expression and HO-1 levels. PDL suppressed renal NF-κB mRNA expression, and NLRP3 inflammasome pathway expression. Moreover, PDL enhanced renal autophagy through upregulating LC3B, AMPK and SIRT-1, and suppressed mTOR, p-AKT mRNA expressions and phosphorylated-p62 levels. Our study confirmed that autophagy suppression mediates DIC-induced AKI via AMPK/mTOR/AKT and NLRP3-inflammasome pathways. Also, PDL's nephroprotective effects could provide a promising therapeutic approach against DIC-induced AKI.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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