Aprepitant boasted a protective effect against olanzapine-induced metabolic syndrome and its subsequent hepatic, renal, and ovarian dysfunction; Role of IGF 1 /p-AKT/FOXO 1 and NFκB/IL-1β/TNF-α signaling pathways in female Wistar albino rats

Olanzapine-induced metabolic syndrome (MS) is a primary risk factor for insulin resistance, hepatorenal damage, and polycystic ovarian syndrome. The objective of the current study was to assess the protective effects of aprepitant (AP) against MS caused by olanzapine and the associated ovarian, rena...

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Published inBiochemical pharmacology Vol. 221; p. 116020
Main Authors Mohyeldin, Reham H, Abdelzaher, Walaa Yehia, Sharata, Ehab E, Mohamed, Hamza M A, Ahmed, Mohamed Y M, Attia, Josef Zekry, Atta, Medhat, Saleh, Rabeh Khairy, Ghallab, Elshimaa A, Marey, Heba, Elrehany, Mahmoud A, Rofaeil, Remon Roshdy
Format Journal Article
LanguageEnglish
Published England 01.03.2024
Subjects
Aprepitant
PCOS
FOXO 1
MS
Hepatorenal injury
IGF 1
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Summary:Olanzapine-induced metabolic syndrome (MS) is a primary risk factor for insulin resistance, hepatorenal damage, and polycystic ovarian syndrome. The objective of the current study was to assess the protective effects of aprepitant (AP) against MS caused by olanzapine and the associated ovarian, renal, and liver dysfunction via modulation of IGF /p-AKT/FOXO and NFκB/IL-1β/TNF-α signaling pathways. AP mitigated all biochemical and histopathological abnormalities induced by olanzapine and resulted in a significant reduction of serum HOMA-IR, lipid profile parameters, and a substantial decrease in hepatic, renal, and ovarian MDA, IL-6, IL-1β, TNF-α, NFκB, and caspase 3. Serum AST, ALT, urea, creatinine, FSH, LH, and testosterone also decreased significantly by AP administration. The FOXO 1 signaling pathway was downregulated in the AP-treated group, while GSH, SOD, and HDL cholesterol levels were elevated.
ISSN:1873-2968