Omarigliptin/rosinidin combination ameliorates cyclophosphamide-induced lung toxicity in rats: The interaction between glucagon-like peptide-1, TXNIP/NLRP3 inflammasome signaling, and PI3K/Akt/FoxO1 axis.

Autor: Abd Elmaaboud MA; Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, Egypt., Kabel AM; Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, Egypt. Electronic address: ahmed.kabal@med.tanta.edu.eg., Borg HM; Physiology Department, Faculty of Medicine, Kafrelsheikh University, Kafr El-Shaikh 33516, Egypt., Magdy AA; Anesthesia and ICU Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt., Kabel SM; Zoology Department, Faculty of Science, Tanta University, Tanta 31527, Egypt., Arafa EA; College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab Emirates; Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman 346, United Arab Emirates., Alsufyani SE; Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia., Arab HH; Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Aug; Vol. 177, pp. 117026. Date of Electronic Publication: 2024 Jun 26.
DOI: 10.1016/j.biopha.2024.117026
Abstrakt: Cyclophosphamide is an anti-neoplastic drug that has shown competence in the management of a broad range of malignant tumors. In addition, it represents a keystone agent for management of immunological conditions. Despite these unique properties, induction of lung toxicity may limit its clinical use. Omarigliptin is one of the dipeptidyl peptidase-4 inhibitors that has proven efficacy in management of diabetes mellitus. Rosinidin is an anthocyanidin flavonoid that exhibited promising results in management of diseases characterized by oxidative stress, inflammation, and apoptosis. The present work investigated the possible effects of omarigliptin with or without rosinidin on cyclophosphamide-induced lung toxicity with an exploration of the molecular mechanisms that contribute to these effects. In a rodent model of cyclophosphamide elicited lung toxicity, the potential efficacy of omarigliptin with or without rosinidin was investigated at both the biochemical and the histopathological levels. Both omarigliptin and rosinidin exhibited a synergistic ability to augment the tissue antioxidant defenses, mitigate the inflammatory pathways, restore glucagon-like peptide-1 levels, modulate high mobility group box 1 (HMGB1)/receptors of advanced glycation end products (RAGE)/nuclear factor kappa B (NF-κB) axis, downregulate the fibrogenic mediators, and create a balance between the pathways involved in apoptosis and the autophagy signals in the pulmonary tissues. In conclusion, omarigliptin/rosinidin combination may be introduced as a novel therapeutic modality that attenuates the different forms of lung toxicities induced by cyclophosphamide.
Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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