Regulation of radiation‐induced liver damage by modulation of SIRT‐1 activity: In vivo rat model

Abstract

Silent information regulator 1 (SIRT-1), a nicotinamide adenine dinucleotidedependent 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.

Photoelectrochemical Biosensor for Histone Deacetylase Sirt1 Detection Based on Polyaspartic Acid-Engaged and Triggered Redox Cycling Amplification and Enhanced Photoactivity of BiVO4 by Gold Nanoparticles and SnS2

“…As a histone deacetylase, Sirt1 enzyme is involved in many important biological processes, such as liver dysfunction . More importantly, the overexpression of Sirt1 has been related to the occurrence of various cancers, including human pancreatic cancer, prostate cancer, and colon cancer. − Therefore, screening the inhibitors of Sirt1 enzyme is particularly important for the therapy of the Sirt1-related diseases.…”

Evaluation of the Reparative Effect of Sinomenine in an Acetaminophen-Induced Liver Injury Model

“…The human protein SIRT-1 is of great importance in the processes of inflammation and neurodegeneration [39]. In the study of El-Sheikh et al [40], they observe that Resveratrol can reduce radiation-induced liver damage by reducing apoptosis and inflammation through the modulation of SIRT1 activity. Moreover, Biel T [41] found that SIRT1 plays a crucial role in preventing ischemic liver injury by suppressing defective autophagy, mitochondrial dysfunction, and hepatocyte death, with its activation dependent on mitofusin-2.…”

The role of sirtuin1 in liver injury: molecular mechanisms and novel therapeutic target

“…This enhances mitochondrial biogenesis and antioxidant responses, evident in the induction of proteins like heme oxygenase-1 (HO-1) and GCLM in drug-induced liver injury scenarios ( Abdelzaher, Ali & El-Tahawy, 2020 ; El Shaffei et al, 2021 ). Furthermore, the research by El-Sheikh et al (2023) expands the protective roles of SIRT1 beyond drug-induced scenarios to include radiation-induced liver damage. In this context, upregulating SIRT1 leads to a suppression of poly ADP-ribose polymerase-1 (PARP-1) and forkhead box O1 (FoxO-1).…”