Calcium voltage-gated channel subunit alpha 1 C and glial fibrillary acidic protein signaling pathways as a selective biomarker in predicting the efficacy of liposomal loaded co-enzyme Q in the autistic rat model

Doaa M Elhefnawei; Ahlam H Mahmoud; Mai O Kadry; Asmaa K Al-Mokaddem; Mohamed A Badawy; Mohamed A El-Desouky

doi:10.1016/j.toxrep.2022.12.003

Calcium voltage-gated channel subunit alpha 1 C and glial fibrillary acidic protein signaling pathways as a selective biomarker in predicting the efficacy of liposomal loaded co-enzyme Q in the autistic rat model

Toxicol Rep. 2022 Dec 7:10:17-26. doi: 10.1016/j.toxrep.2022.12.003. eCollection 2023.

Authors

Doaa M Elhefnawei¹, Ahlam H Mahmoud¹, Mai O Kadry¹, Asmaa K Al-Mokaddem², Mohamed A Badawy³, Mohamed A El-Desouky⁴

Affiliations

¹ Department of Therapeutic Chemistry, National Research Centre, Dokki, Giza 12622, Egypt.
² Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt.
³ Department of Biochemistry, Faculty of Science, Cairo University, Egypt.
⁴ Department of Organic chemistry, Faculty of Science, Cairo University, Egypt.

Abstract

Autism spectrum disorder (ASD) is an extreme neuropsychotic disturbance with both environmental and genetic origins. Sodium propionate (PPA) a metabolic bioproduct of gut microbiota is well-thought-out as a successful autism animal model. Nevertheless, Liposomal drug delivery system possess the advantagous of biocompatibility, targeting organs, ability to carry large drug payloads and skipping macrophages for this purpose the current study was carried out to investigate the hypothesis that Calcium Voltage-Gated channel subunit alpha 1 C (CACNA1C) and glial fibrillary acidic protein (GFAP) signaling pathways crosstalk with the efficacy of Co-enzyme Q10 (Co-Q10) and liposomal loaded Co-enzyme Q10 (L Co-Q10) in PPA mediated autistic rat model. Autism was conducted by buffered PPA (500 mg/Kg b.wt) daily for 5 consecutive days subsequently treatment via Co-Q10 in a dose of (10 mg/kg b.wt) and L Co-Q10 (2 mg/kg b.wt) for four weeks then the autistic model was followed for signs of autism at different time intervals of (one, two and four weeks). The control, PPA intoxicated, and treated groups were subjected to behavioral tests (Y-Maze and open field), antioxidant analysis, gene expression analysis, and histological examination at different time intervals of the study. The results revealed that Co-Q10 and L Co-Q10 significantly elevated antioxidative stress biomarkers, comprising superoxide dismutase (SOD), glutathione (GSH), and total antioxidant capacity (TAC). In addition, they significantly ameliorated the oxidative stress biomarker malondialdehyde (MDA). Meanwhile, they significantly downregulated GFAP and CACNA1C mRNA gene expressions, Co-Q10 and LCo-Q10 showed improvement in almost brain regions post PPA histopathological alterations, even better results were manifested via LCo-Q10 groups. These results showed the superiority of LCo-Q10 over Co-Q10 in competing autism. In conclusion: The administration of anti-inflammatory and antioxidant agents such as Co-Q10 and L Co-Q10 may represent a promising strategy to counteract pathological behaviors in ASD model via targeting organs, increasing retention time, and reducing side effects.

Keywords: Autism spectrum disorder; CACNA1C; Co-enzyme Q10; GFAP; Liposomal co-enzyme Q10.