Omarigliptin attenuates rotenone-induced Parkinson's disease in rats: Possible role of oxidative stress, endoplasmic reticulum stress and immune modulation.

Autor: Michel HE; Pharmacology and Toxicology Department, Faculty of Pharmacy, Ain Shams University, Organization of African Unity Street, Abassia, Cairo, 11566, Egypt. Electronic address: heidieffat@pharma.asu.edu.eg., Tadros MM; Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Or-ganization of African Unity Street, Abassia, Cairo, 11566, Egypt., Hendy MS; Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt; The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt., Mowaka S; Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt; The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt; Analytical Chemistry Department, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo, 11795, Egypt., Ayoub BM; Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt; The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt. Electronic address: Bassam.ayoub@bue.edu.eg.
Jazyk: angličtina
Zdroj: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2022 Jun; Vol. 164, pp. 113015. Date of Electronic Publication: 2022 Apr 16.
DOI: 10.1016/j.fct.2022.113015
Abstrakt: The current study aimed to explore the potential neuroprotective effect of omarigliptin (OG), an antidiabetic drug that crosses the blood-brain barrier (BBB), in a Parkinson's disease (PD) rotenone-based rat-model. Results showed that OG attenuated motor impairment, histological aberrations, α-synuclein accumulation, and rescued the dopaminergic neurons in rotenone-administered rats. Furthermore, OG halted rotenone-induced oxidative stress; as shown by reduced lipid peroxidation, decline in the oxidative stress sensor (nuclear factor erythroid 2-related factor 2) and its downstream heme oxygenase-1. In addition, OG abrogated neuroinflammation and apoptosis in rotenone-treated rats. Moreover, OG ameliorated endoplasmic reticulum (ER) stress in rotenone-administered rats; as evidenced by reduced levels of ER resident proteins such as glucose-regulated protein 78, C/EBP homologous protein and apoptotic caspase-12. In conclusion, this study implies repurposing of OG, as a novel neuroprotective agent due to its antioxidant properties, its effects on ER stress in addition to its anti-inflammatory and anti-apoptotic activities.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: