Sexual Dimorphism in Doxorubicin-induced Systemic Inflammation: Implications for Hepatic Cytochrome P450 Regulation
Abstract
:1. Introduction
2. Results
2.1. Effect of DOX Treatment on Inflammatory Markers
2.2. Effect of DOX Treatment on Cyp1 Family Expression
2.3. Effect of DOX Treatment on Cyp2 Family Expression
2.4. Effect of DOX Treatment on Cyp4a Sub-family Expression
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Measurement of Inflammatory Markers
4.3. RNA Extraction and Real-time PCR
4.4. Protein Extraction and Western Blotting
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AhR | Aryl hydrocarbon Receptor |
Cox-2 | Cyclooxygenase-2 |
CYP | Cytochrome P450 |
DOX | Doxorubicin |
IL-6 | Interleukin-6 |
TNF-alpha | Tumor Necrosis Factor-alpha |
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24 h Post-DOX | ||||||
DOX Effect | Sex Effect | Interaction | ||||
F (1, 28) | p Value | F (1, 28) | p Value | F (1, 28) | p Value | |
Cyp1a1 | 14.75 | 0.0006 | 14.61 | 0.0007 | 9.855 | 0.004 |
Cyp1b1 | ns | ns | ns | |||
Cyp2c29 | 82.54 | <0.0001 | ns | 5.58 | 0.0254 | |
Cyp2e1 | 36.63 | <0.0001 | 8.817 | 0.0061 | ns | |
Cyp4a10 | 114.9 | <0.0001 | 20.01 | 0.0001 | 11.67 | 0.002 |
Cyp4a12 | 11.42 | 0.0022 | 229.9 | <0.0001 | 11.45 | 0.0021 |
72 h Post-DOX | ||||||
DOX Effect | Sex Effect | Interaction | ||||
F (1, 13) | p Value | F (1, 13) | p Value | F (1, 13) | p Value | |
Cyp1a1 | ns | ns | ns | |||
Cyp1b1 | 9.828 | 0.0079 | ns | ns | ||
Cyp2c29 | 8.005 | 0.0142 | ns | 7.136 | 0.0192 | |
Cyp2e1 | ns | ns | ns | |||
Cyp4a10 | 6.711 | 0.0224 | ns | ns | ||
Cyp4a12 | 153.1 | <0.0001 | 202.6 | <0.0001 | 151.4 | <0.0001 |
Gene | Forward Primer (5′–3′) | Reverse Primer (5′–3’) |
---|---|---|
IL-6 | CCA GAG ATA CAA AGA AAT GAT GG | ACT CCA GAA GAC CAG AGG AAA T |
TNF-alpha | CCA GAC CCT CAC ACT CAG ATC A | CAC TTG GTG GTT TGC TAC GAC |
Cox-2 | CTG GTG CCT GGT CTG ATG ATG | GGC AAT GCG GTT CTG ATA CTG |
Cyp1a1 | GGT TAA CCA TGA CCG GGA ACT | TGC CCA AAC CAA AGA GAG TGA |
Cyp1b1 | AAT GAG GAG TTC GGG CGC ACA | GGC GTG TGG AAT GGT GAC AGG |
Cyp2c29 | TGG TCC ACC CAA AAG AAA TTG A | GCA GAG AGG CAA ATC CAT TCA |
Cyp2e1 | CCC AAG TCT TTA ACC AAG TTG GC | CTT CCA TGT GGG TCC ATT ATT GA |
Cyp4a10 | GTG CTG AGG TGG ACA CAT TCA T | TGT GGC CAG AGC ATA GAA GAT C |
Cyp4a12 | TGA CCC CAG CTT TCC ACT ATG | TTG TTC AGG TCC TCA ACT GCC |
Beta-actin | TAT TGG CAA CGA GCG GTT CC | GGC ATA GAG GTC TTT ACG GAT GTC |
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Grant, M.K.O.; Abdelgawad, I.Y.; Lewis, C.A.; Zordoky, B.N. Sexual Dimorphism in Doxorubicin-induced Systemic Inflammation: Implications for Hepatic Cytochrome P450 Regulation. Int. J. Mol. Sci. 2020, 21, 1279. https://doi.org/10.3390/ijms21041279
Grant MKO, Abdelgawad IY, Lewis CA, Zordoky BN. Sexual Dimorphism in Doxorubicin-induced Systemic Inflammation: Implications for Hepatic Cytochrome P450 Regulation. International Journal of Molecular Sciences. 2020; 21(4):1279. https://doi.org/10.3390/ijms21041279
Chicago/Turabian StyleGrant, Marianne K.O., Ibrahim Y. Abdelgawad, Christine A. Lewis, and Beshay N. Zordoky. 2020. "Sexual Dimorphism in Doxorubicin-induced Systemic Inflammation: Implications for Hepatic Cytochrome P450 Regulation" International Journal of Molecular Sciences 21, no. 4: 1279. https://doi.org/10.3390/ijms21041279