Details

Autor(en) / Beteiligte

• Zaky, Doaa A.
• Sayed, Rabab H.
• Mohamed, Yasmin S.

Titel

Liraglutide limits the immunogenic cell death-mediated ROS propagation and PI3K/AKT inactivation after doxorubicin-induced gonadotoxicity in rats: Involvement of the canonical Hedgehog trajectory

Ist Teil von

• International immunopharmacology, 2023-06, Vol.119, p.110212-110212, Article 110212

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2023

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• •Liraglutide modulated the canonical Hh signaling in DXR-induced gonadotoxicity.•Liraglutide potentiated the PI3K/AKT/p-GSK3β cascade.•Liraglutide relieved the oxidative burden-induced by the DXR. Chemotherapy-accompanied reproductive dysfunction has lately begun to draw the attention of the scientific community owing to the irreversible impact on the patient’s quality of life. Here we tended to investigate the potential role of liraglutide (LRG) in modulating the canonical Hedgehog (Hh) signaling in doxorubicin (DXR)-induced gonadotoxicity in rats. Female virgin Wistar rats were divided into 4 groups; control, DXR-treated (25 mg/kg, single i.p. injection), LRG-treated (150 μg/Kg/day, s.c) and itraconazole (ITC; 150 mg/kg/day, p.o)-pretreated group, as the Hh pathway inhibitor. Treatment with LRG potentiated the PI3K/AKT/p-GSK3β cascade and relieved the oxidative burden-induced by the DXR-driven immunogenic cell death (ICD). LRG also upregulated the expression of the Desert hedgehog ligand (DHh) and the patched-1 (PTCH1) receptor and augmented the protein level of Indian hedgehog (IHh) ligand, Gli1 and cyclin-D1 (CD1). Besides, hypertranscription of IHh, DHh, Ptch1, Smo, Gli1/2 and CD1 genes along with a transcriptional recession of Gli3 gene were reported in LRG-treated group. ITC pre-administration partially abrogated this positive effect of LRG, proving the implication of the examined pathway. Microscopically, LRG ameliorated the follicular atresia noticed in the DXR group; effect that was, at least partially, declined by ITC pre-treatment. These findings end to a conclusion that LRG treatment might hinder the DXR-associated reproductive toxicity, resultant from ROS generated by the cells undergoing ICD, and trigger follicular growth and repair by the PI3K/AKT- dependent switching-on of the canonical Hh pathway.