التفاصيل البيبلوغرافية
| العنوان: |
Regulation of radiation‐induced liver damage by modulation of SIRT‐1 activity: In vivo rat model. |
| المؤلفون: |
El‐Sheikh, Marwa M., Abdel‐Naby, Doaa H., El‐Hazek, Rania M., El‐Ghazaly, Mona A. |
| المصدر: |
Cell Biochemistry & Function; Jan2023, Vol. 41 Issue 1, p67-77, 11p |
| مصطلحات موضوعية: |
NICOTINAMIDE, POLY(ADP-ribose) polymerase, ANIMAL disease models, ELLAGIC acid, GAMMA rays, LIVER, LACTATE dehydrogenase |
| مستخلص: |
Silent information regulator 1 (SIRT‐1), a nicotinamide adenine dinucleotide‐dependent deacetylase, was found to regulate cell apoptosis, inflammation, and oxidative stress response in living organisms. Therefore, the role of SIRT‐1 in regulating forkhead box O/poly ADP‐ribose polymerase‐1 (FOXO‐1/PARP‐1) signaling could provide the necessary validation for developing new pharmacological targets for the promotion or inhibition of SIRT‐1 activity toward radiation sensitivity. In the present study, the SIRT‐1 signaling pathway is being investigated to study the possible modulatory effect of resveratrol (RSV, SIRT‐1 activator) versus nicotinamide (NAM, SIRT‐1 inhibitor) in case of liver damage induced by whole‐body gamma irradiation. Rats were exposed to 6 Gy gamma radiation after being pretreated with either RSV (10 mg/kg/day) or NAM (100 mg/kg/day) for 5 days, and subsequent examining hepatic morphological changes and apoptotic markers were assessed. The expression of SIRT‐1, FOXO‐1, and cleaved PARP‐1 in the liver was analyzed. RSV improved radiation‐induced apoptosis, mitochondrial dysfunction, and inflammation signified by low expression of caspase‐3, lactate dehydrogenase, complex‐I activity, myeloperoxidase, and total nitric oxide content. RSV increased the expression of SIRT‐1, whereas cleaved PARP‐1 and FOXO‐1 were suppressed. These protective effects were suppressed by inhibition of SIRT‐1 activity using NAM. These findings suggest that RSV can attenuate radiation‐induced hepatic injury by reducing apoptosis and inflammation via SIRT‐1 activity modulation. Significance statement: The present study emerges the molecular mechanism and the energetic metabolism at the expense of hepatic tissue damage caused by acute irradiation. We have broadly investigated the interplay between activation/inhibition of the SIRT‐1/FOXO signaling pathway and its consequence on the modulation of the inflammatory response and cellular death. This study may be of great significance for routinely used NAD+‐modifying medicines, like resveratrol and nicotinamide, enhancing the radiosensitization toward cancer resistance and how far the treatment regimen might affect vital organs like the liver during the radiotherapy. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
