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
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 adva...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Toxicology Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221475002200227X |
| _version_ | 1827920510552375296 |
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| author | Doaa M. Elhefnawei Ahlam H. Mahmoud Mai O. Kadry Asmaa K. AL-Mokaddem Mohamed A. Badawy Mohamed A. EL-Desouky |
| author_facet | Doaa M. Elhefnawei Ahlam H. Mahmoud Mai O. Kadry Asmaa K. AL-Mokaddem Mohamed A. Badawy Mohamed A. EL-Desouky |
| author_sort | Doaa M. Elhefnawei |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T04:10:59Z |
| format | Article |
| id | doaj.art-8bbf5139417c482d9ffa6a3076785585 |
| institution | Directory Open Access Journal |
| issn | 2214-7500 |
| language | English |
| last_indexed | 2024-03-13T04:10:59Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Toxicology Reports |
| spelling | doaj.art-8bbf5139417c482d9ffa6a30767855852023-06-21T06:54:59ZengElsevierToxicology Reports2214-75002023-01-01101726Calcium 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 modelDoaa M. Elhefnawei0Ahlam H. Mahmoud1Mai O. Kadry2Asmaa K. AL-Mokaddem3Mohamed A. Badawy4Mohamed A. EL-Desouky5Department of Therapeutic Chemistry, National Research Centre, Dokki, Giza 12622, EgyptDepartment of Therapeutic Chemistry, National Research Centre, Dokki, Giza 12622, EgyptDepartment of Therapeutic Chemistry, National Research Centre, Dokki, Giza 12622, Egypt; Corresponding author.Department of Pathology, Faculty of Veterinary Medicine, Cairo University, EgyptDepartment of Biochemistry, Faculty of Science, Cairo University, EgyptDepartment of Organic chemistry, Faculty of Science, Cairo University, EgyptAutism 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.http://www.sciencedirect.com/science/article/pii/S221475002200227XAutism spectrum disorderCo-enzyme Q10Liposomal co-enzyme Q10CACNA1CGFAP |
| spellingShingle | Doaa M. Elhefnawei Ahlam H. Mahmoud Mai O. Kadry Asmaa K. AL-Mokaddem Mohamed A. Badawy Mohamed A. EL-Desouky 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 Toxicology Reports Autism spectrum disorder Co-enzyme Q10 Liposomal co-enzyme Q10 CACNA1C GFAP |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Autism spectrum disorder Co-enzyme Q10 Liposomal co-enzyme Q10 CACNA1C GFAP |
| url | http://www.sciencedirect.com/science/article/pii/S221475002200227X |
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