journal article·2026-01-02

Neuroprotective Activities of Nigella sativa Ethanolic Extract and Telmisartan Against Fipronil-Induced Neurotoxicity in Rats via Regulation of Apoptosis, Endosomal Micro-autophagy, and miRNA-137-5p

Aya H Rohiem, Hebatallah M Saad, Duaa Eliwa, Neveen R Ashoura, Asmaa A Aboushouk, Omnya Elhussieny, Hanan A Edres, Hassan kazim Ali Althabet, Esraa A Salem

Microscopy and Microanalysis· Volume 32· Issue 1
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Abstract

Abstract The purpose of our study was to investigate the neuroprotective effects of Nigella sativa (NSt) ethanolic extract (200 mg/kg) and/or Telmisartan(Tel) (10 mg/kg) against fipronil (Fip) (9.7 mg/kg)-induced neurobehavioral toxicity in rats, besides exploring the underlying mechanistic signaling pathways. Our results showed that the phytochemical analysis of NSt ethanolic extract by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS) revealed 43 compounds, mainly alkaloids, phenolics, terpenoids, fatty acids and flavonoids. While in our in vivo model of neurotoxicity, the combination of NSt and Tel effectively restored neurobehavioral alterations in rotarod, open field and T-maze tests. Additionally, the cotreatments of NSt and Tel significantly decreased acetylcholine, tumor necrosis factors-α, interleukin (IL)-6, IL-1β, MDA, BAX, P62, LC3B and IBA-1. Conversely, they significantly upregulated GABA, brain-derived neurotrophic factor, superoxide dismutase, catalase, glutathione peroxidase and antiapoptotic BCl2, P70S6K and miRNA137-5P without significant change in mTOR expression in hippocampus. Also, they ameliorated pathological alterations as detected by H&E staining, reduced glial fibrillary acidic protein and caspase-3 immunoreactivity. Electron microscopic examination of the combination group revealed the restoration of nuclear and mitochondrial structures with less glial activation and multivesicular bodies. In conclusion, the combination of NSt and Tel are notable agents in mitigating hippocampal neuronal necrosis and astrogliosis and reduced Fip-induced neurotoxicity.
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Research context

OpenAlex topics: Nigella sativa pharmacological applications · Chemotherapy-induced organ toxicity mitigation · Saffron Plant Research Studies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Physiology, Faculty of Veterinary Medicine, Alexandria University , Apis, Alexandria 21944 ,

Department of Pathology, Faculty of Veterinary Medicine, Matrouh University , Marsa Matrouh 51744 ,

Department of Pharmacognosy, Faculty of Pharmacy, Tanta University , Tanta 31527 , (D.E.)

Department of Pharmacology, Faculty of Veterinary Medicine, Alexandria University , Apis, Alexandria 21944 ,

Department of Pathology, Faculty of Veterinary Medicine, Alexandria University , Apis, Alexandria 21944 ,

Department of Histology and Cytology, Faculty of Veterinary Medicine, Matrouh University , Matrouh 51744 ,

Department of Biochemistry, Faculty of Veterinary Medicine, Alexandria University , Apis, Alexandria 21944 ,

Respiratory Therapy Program, Batterjee Medical College , Aseer 21442 ,

Department of Medical Physiology, Faculty of Medicine, Menoufia University , Shebeen ElKom 32511 ,

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