Journal Article

Ameliorative Effect of Chitosan/Spirulina platensis Ethanolic Extract Nanoformulation against Cyclophosphamide-Induced Ovarian Toxicity: Role of PPAR-γ/Nrf-2/HO-1 and NF-kB/TNF-α Signaling Pathways

El-Masry, Thanaa A., Ibrahim, Hanaa A., Almukainzi, May, Saleh, Asmaa, El-Nagar, Maysa M. F., El Zahaby, Enas I., Saad, Hebatallah M.

2024

Overview

Cyclophosphamide (CP) is an anticancer drug that causes infertility disorders. This study was designed to evaluate a nanoformulation of chitosan with an ethanolic extract from Spirulina platensis in terms of its protection against cyclophosphamide-induced ovarian toxicity. Nine groups of female Wistar rats were randomly assigned as follows: 1: control vehicle, 2: chitosan polymer, 3: telmisartan, 4: Spirulina platensis extract, 5: nanoformulation of the Spirulina platensis, and 6: single injection of CP; groups 7, 8, and 9 received the same treatments as those used in groups 3, 4, and 5, respectively, with a single dose of CP (200 mg/kg, I.P). The results displayed that the CP treatment decreased estradiol, progesterone, anti-mullerian hormone, and GSH content, and it downregulated PPAR-γ, Nrf-2, and HO-1 gene expression. In addition, the CP treatment caused an increase in the FSH, LH, and MDA levels. In the same manner, the protein expression of caspase-3, NF-kB, and TNF-α was upregulated in response to the CP treatment, while PPAR-γ was downregulated in comparison with the control. The rats treated with SPNPs exhibited a substantial reduction in the detrimental effects of oxidative stress and inflammation of the ovarian tissue. This study’s conclusions showed that SPNPs counteracted the effects of CP, preventing the death of ovarian follicles and restoring the gonadotropin hormone balance and normal ovarian histological appearance.

• Publisher: MDPI AG,MDPI
• Subject: 17β-Estradiol / Amino acids / Animals / anti-Mullerian hormone / Antineoplastic drugs / Antioxidants / Arthrospira platensis / Caspase-3 / Chitosan / Chitosan - chemistry / Chitosan - pharmacology / Cyanobacteria / Cyclophosphamide / Cyclophosphamide - toxicity / death / Down-regulation / estradiol / Estrogen / Ethanol - chemistry / Female / females / Flavonoids / Follicle-stimulating hormone / Follicles / GA-binding protein / Gene expression / Gonadotropins / Heme oxygenase (decyclizing) / Heme Oxygenase (Decyclizing) - metabolism / histology / Hormones / Infertility / inflammation / Lipid peroxidation / Luteinizing hormone / Molecular weight / Nanoparticles / NF-E2-Related Factor 2 - metabolism / NF-kappa B - metabolism / NF-κB protein / Ovaries / Ovary - drug effects / Ovary - metabolism / Ovary - pathology / Oxidative stress / Oxidative Stress - drug effects / Particle size / Peroxisome proliferator-activated receptors / Pituitary (anterior) / Polymers / PPAR gamma - metabolism / Progesterone / protein synthesis / Rats / Rats, Wistar / Scanning electron microscopy / Sex hormones / Side effects / Signal Transduction - drug effects / Spirulina / Spirulina platensis / Telmisartan / Toxicity / transcription factor NF-kappa B / Tumor necrosis factor / Tumor Necrosis Factor-alpha - metabolism / Tumor necrosis factor-α