Unraveling the Hippocampal Molecular and Cellular Alterations behind Tramadol and Tapentadol Neurobehavioral Toxicity
Abstract
:1. Introduction
2. Results
2.1. Repeated Exposure to Tramadol and Tapentadol Causes Oxidative Stress at the Systemic and Hippocampal Levels
2.2. Repeated Exposure to Tramadol and Tapentadol Affects Neurotoxicity and Neuromodulation Pathways
3. Discussion
4. Materials and Methods
4.1. Experimental Models and Design
4.2. Sample Collection and Processing
4.3. Quantification of Serum Oxidative Damage Parameters
4.4. Quantification of Oxidative Damage Parameters in Hippocampal DNA Samples
4.5. Quantification of Serum Biochemical Parameters
4.6. Gene Expression Analysis in the Hippocampal Formation through qRT-PCR
4.7. GFAP and CD11b Immunohistochemistry in Hippocampal Formation Sections
4.8. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene | Primer | Nucleotide Sequence (5′ → 3′) | References |
---|---|---|---|
ITGAM [cluster of differentiation molecule 11b (CD11b)] | Fw | CTGCCTCAGGGATCCGTAAAG | [110] |
Rev | CCTCTGCCTCAGGAATGACATC | ||
PTGS2 [cyclooxygenase-2 (COX-2)] | Fw | TGCGATGCTCTTCCGAGCTGTGCT | [111] |
Rev | TCAGGAAGTTCCTTATTTCCTTTC | ||
CASP3 (caspase-3) | Fw | GTGGAACTGACGATGATATGGC | [112] |
Rev | CGCAAAGTGACTGGATGAACC | ||
GFAP (glial fibrillary acidic protein) | Fw | CACTCAGTACGAGGCAGTGG- | [113] |
Rev | ACTCAAGGTCGCAGGTCAAG | ||
OPRM1 (µ-opioid receptor 1) | Fw | AATCGTCAACGTCTGCAACTGG | [114] |
Rev | GAACGTGAGGGTGCAATCTATGG | ||
NMDAR1 (N-methyl-d-aspartate receptor subunit 1) | Fw | GCTGTACCTGCTGGACCGCT | [115] |
Rev | GCAGTGTAGGAAGCCACTATGATC | ||
HRH1 (histamine H1 receptor) | Fw | CTGGTCACAGTGGGCCTCAA | [116] |
Rev | CTGCCACAGACAGGCTGACAA | ||
HTR1A (5-hydroxytryptamine receptor 1A) | Fw | TCCGACGTGACCTTCAGCTA | [117] |
Rev | GCCAAGGAGCCGATGAGATA | ||
HTR7 (5-hydroxytryptamine receptor 7) | Fw | CCGTGAGGCAGAATGGGAAATGTAT | [118] |
Rev | CACTGCGGTGGAGTAGATCGTGTAGC | ||
CNR1 (cannabinoid receptor 1) | Fw | AGGAGCAAGGACCTGAGACA | [119] |
Rev | TAACGGTGCTCTTGATGCAG | ||
STAT3 (signal transducer and activator of transcription protein 3) | Fw | CAAAGAAAACATGGCCGGCA | [120] |
Rev | GGGGGCTTTGTGCTTAGGAT | ||
18S rRNA (18S subunit of ribosomal RNA) | Fw | GCAATTATTCCCCATGAACG | [121,122] |
Rev | GGCCTCACTAAACCATCCAA |
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Soares-Cardoso, C.; Leal, S.; Sá, S.I.; Dantas-Barros, R.; Dinis-Oliveira, R.J.; Faria, J.; Barbosa, J. Unraveling the Hippocampal Molecular and Cellular Alterations behind Tramadol and Tapentadol Neurobehavioral Toxicity. Pharmaceuticals 2024, 17, 796. https://doi.org/10.3390/ph17060796
Soares-Cardoso C, Leal S, Sá SI, Dantas-Barros R, Dinis-Oliveira RJ, Faria J, Barbosa J. Unraveling the Hippocampal Molecular and Cellular Alterations behind Tramadol and Tapentadol Neurobehavioral Toxicity. Pharmaceuticals. 2024; 17(6):796. https://doi.org/10.3390/ph17060796
Chicago/Turabian StyleSoares-Cardoso, Cristiana, Sandra Leal, Susana I. Sá, Rita Dantas-Barros, Ricardo Jorge Dinis-Oliveira, Juliana Faria, and Joana Barbosa. 2024. "Unraveling the Hippocampal Molecular and Cellular Alterations behind Tramadol and Tapentadol Neurobehavioral Toxicity" Pharmaceuticals 17, no. 6: 796. https://doi.org/10.3390/ph17060796