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

被引：4
作者：
Michel, Haidy E. [1 ]
Tadros, Mariam M. [2 ]
Hendy, Moataz S. [3 ,4 ]
Mowaka, Shereen [3 ,4 ,5 ]
Ayoub, Bassam M. [3 ,4 ]
机构：
[1] Ain Shams Univ, Fac Pharm, Pharmacol & Toxicol Dept, Org African Unity St, Cairo 11566, Egypt
[2] Ain Shams Univ, Fac Pharm, Pharmaceut Analyt Chem Dept, Ganizat African Unity St, Cairo 11566, Egypt
[3] British Univ Egypt, Fac Pharm, Pharmaceut Chem Dept, Cairo 11837, Egypt
[4] British Univ Egypt, Fac Pharm, Ctr Drug Res & Dev CDRD, Cairo 11837, Egypt
[5] Helwan Univ, Fac Pharm, Analyt Chem Dept, Cairo 11795, Egypt
来源：
FOOD AND CHEMICAL TOXICOLOGY | 2022年 / 164卷
关键词：
Repurposing; Parkinson's disease; Rotenone; Omarigliptin; Endoplasmic reticulum stress; DIPEPTIDYL PEPTIDASE-4 INHIBITOR; GLUCAGON-LIKE PEPTIDE-1; CELL-DEATH; MODEL; APOPTOSIS; PROTECTS; ER; SITAGLIPTIN; FEATURES; AGONISTS;
D O I：
10.1016/j.fct.2022.113015
中图分类号：
TS2 [食品工业];
学科分类号：
0832 ;
摘要：
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, alpha-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 neumprotective agent due to its antioxidant properties, its effects on ER stress in addition to its anti-inflammatory and anti-apoptotic activities.
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页数：12
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