Antidiabetic Drugs Can Reduce the Harmful Impact of Chronic Smoking on Post-Traumatic Brain Injuries
Abstract
:1. Introduction
2. Results
2.1. Effect of MF and RSG on Body Weight and Fasting Blood Glucose Levels of Premorbid TS-Exposed and TBI-Induced Mice
2.2. MF and RSG Upregulate NRF2 and Its Downstream Effector Molecules
2.3. MF and RSG Reduce OS and Inflammatory Responses Enhanced by Premorbid TS Exposure
2.4. MF and RSG Reduced the Negative Impact of Chronic Premorbid TS Exposure on BBB Disruption by TBI
2.5. Downregulation of Thrombomodulin and UCH-L1 Prompted by Chronic TS Exposure in TBI-Induced Mice Is Reduced by MF and RSG
2.6. MF and RSG Decrease the Negative Effect of Chronic TS Exposure on the Loss of Motor Activity and Recovery Post-TBI
3. Discussion
4. Materials and Methods
4.1. Reagents and Materials
4.2. Experimental Design
4.3. Induction of Head Injury in Mice
4.4. Rosiglitazone and Metformin Treatment In Vivo
4.5. Fasting Blood Glucose Level Analysis
4.6. Open Field Test
4.7. Blood Collection and Brain Isolation
4.8. Hematoxylin and Eosin (H&E) and Nissl Staining
4.9. Preparation of Protein Extracts, ELISA, and Zymography
4.10. RNA Extraction and Quantitative Real-Time Polymerase Chain Reaction (RT-PCR)
4.11. Glutathione Levels Measurement
4.12. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ARE | Antioxidative Response Element |
BBB | Blood–Brain Barrier |
CNS | Central Nervous System |
ELISA | Enzyme-Linked Immunosorbent Assay |
HO-1 | Heme Oxygenase 1 |
H&E | Hematoxylin and Eosin |
ICAM-1 | Intercellular Adhesion Molecule-1 |
KEAP1 | Kelch-Like ECH Associated Protein 1 |
mBMEC | Mouse Brain Microvascular Endothelial Cells |
MF | Metformin |
MMP-9 | Matrix Metalloproteinase-9 |
MPO | Myeloperoxidase |
NF-κB | Nuclear Factor kappa B |
NQO-1 | NAD(P)H: Quinone reductase I |
NRF2 | Nuclear Factor erythroid-2 related Factor 2 |
OS | Oxidative Stress |
PECAM-1 | Platelet Endothelial Cell Adhesion Molecule 1 |
PPARγ | Peroxisome Proliferator-Activated Receptor |
ROS | Reactive Oxygen Species |
RSG | Rosiglitazone |
RT-PCR | Real-Time Polymerase Chain Reaction |
SOD | Superoxide Dismutase |
TBI | Traumatic Brain Injury |
TJ | Tight Junction |
TS | Tobacco Smoking |
UCH-L1 | Ubiquitin C-terminal Hydrolase L1 |
VCAM-1 | Vascular Cell Adhesion Protein 1 |
ZO-1 | Zonulae Occludentes-1 |
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TBI Control | TBI + TS | TBI + TS + MF100 | TBI + TS + MF200 | TBI + TS + RSG10 | TBI + TS + RSG20 | |
---|---|---|---|---|---|---|
TBI | √ | √ | √ | √ | √ | √ |
TS Exposure | - | √ | √ | √ | √ | √ |
MF 100 mg/kg | - | - | √ | - | - | - |
MF 200 mg/kg | - | - | - | √ | - | - |
RSG 10 mg/kg | - | - | - | - | √ | - |
RSG 20 mg/kg | - | - | - | - | - | √ |
Target Gene | Forward | Reverse |
---|---|---|
NRF2 | 5′- GGC TCA GCA CCT TGT ATC TT -3′ | 5′- CAC ATT GCC ATC TCT GGT TTG -3′ |
NQO-1 | 5′- GAG AAG AGC CCT GAT TGT ACT G -3′ | 5′- ACC TCC CAT CCT CTC TTC TT -3′ |
HO-1 | 5′- CTC CCT GTG TTT CCT TTC TCT C -3′ | 5′- GCT GCT GGT TTC AAA GTT CAG -3′ |
NF-kB | 5′- AGA CAT CCT TCC GCA AAC TC -3′ | 5′- TAG GTC CTT CCT GCC CAT AA -3′ |
Claudin-5 | 5′- GGT GAA GTA GGC ACC AAA CT -3′ | 5′- TTT CTC CAG CTG CCC TTT C -3′ |
Occludin | 5′- CAG CAG CAA TGG TAA CCT AGA G -3′ | 5′- CAC CTG TCG TGT AGT CTG TTT C -3′ |
VCAM-1 | 5′- GAG GGA GAC ACC GTC ATT ATC -3′ | 5′- CGA GCC ATC CAC AGA CTT TA -3′ |
PECAM-1 | 5′- CAA CAG AGC CAG CAG TAT GA -3′ | 5′- TGA CAA CCA CCG CAA TGA -3′ |
ZO-1 | 5′- CAT TAC GAC CCT GAA GAG GAT G -3′ | 5′- AGC AGG AAG ATG TGC AGA AG -3′ |
Β-Actin | 5′- GAG GTA TCC TGA CCC TGA AGT A -3′ | 5′- CAC ACG CAG CTC ATT GTA GA -3′ |
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Sivandzade, F.; Alqahtani, F.; Dhaibar, H.; Cruz-Topete, D.; Cucullo, L. Antidiabetic Drugs Can Reduce the Harmful Impact of Chronic Smoking on Post-Traumatic Brain Injuries. Int. J. Mol. Sci. 2023, 24, 6219. https://doi.org/10.3390/ijms24076219
Sivandzade F, Alqahtani F, Dhaibar H, Cruz-Topete D, Cucullo L. Antidiabetic Drugs Can Reduce the Harmful Impact of Chronic Smoking on Post-Traumatic Brain Injuries. International Journal of Molecular Sciences. 2023; 24(7):6219. https://doi.org/10.3390/ijms24076219
Chicago/Turabian StyleSivandzade, Farzane, Faleh Alqahtani, Hemangini Dhaibar, Diana Cruz-Topete, and Luca Cucullo. 2023. "Antidiabetic Drugs Can Reduce the Harmful Impact of Chronic Smoking on Post-Traumatic Brain Injuries" International Journal of Molecular Sciences 24, no. 7: 6219. https://doi.org/10.3390/ijms24076219