Resveratrol Modulates the Inflammatory Profile of Immune Responses and Circulating Endothelial Cells’ (CECs’) Population During Acute Whole Body Gamma Irradiation

Abstract

Wistar rats were whole body irradiated with a single dose of 2 Gy post administration with 10 or 100 mg/kg of resveratrol (RSV) intraperitoneally for 30 days. Rats’ livers were dissected and processed to analyze immune response profiles of Th1, Th2, Th9, Th17, and Th22 by flow cytometry. In addition, peripheral blood samples were collected and circulating endothelial cells (CECs) were counted as an indicator for endothelial damage. Results demonstrated that resveratrol at 100 mg/kg enhanced liver immunological response influenced by irradiation by inducing Th2 immune response that was revealed by an increase in IL-10 secretion to more than 5,000 pmol/ml post irradiation. Results also indicated that RSV, at a dose of 100 mg/kg, decreased levels of the main pro-inflammatory cytokines such as INF- γ , IL-22, IL-17A, and GM-CSF post irradiation. In addition, the same RSV was bound to upregulate the expression of IL-10 mRNA in isolated Kupffer cells (KCs) and their secretion of IL-10 post irradiation. The result demonstrated that KCs were the central source of this anti-inflammatory response mediated mainly by IL10. These results, proposed for the first time, clearly states that RSV promotes IL-10 mediated immune resolution by Kupffer cells and not by hepatocytes. This implies that KCs have a crucial role in radiotherapy. Additionally, this study showed that RSV had an anti-apoptotic effect through re-increasing the number of CECs, which is implicated in irradiation damage. Result of the current work discloses novel findings about the potential of RSV as a radio-protector agent of a natural origin and suggests novel roles of KCs as a pharmacological target during radiation exposure.

<i>Trans</i>-resveratrol reduced hepatic oxidative stress in an animal model without inducing an ‍upregulation of nuclear factor erythroid 2-‍related factor 2

“…On the other side, rats exposed to 2 Gy dose of gamma radiation and supplemented with resveratrol 100 mg/kg of resveratrol (RSV) intraperitoneally for 30 days showed an upregulation of IL-6 produced mainly by Th2 cells in rat liver. (35) In this study, the authors suggested that this increase in IL-6 may be involved in tissue repair and regeneration post-irradiation. In our study, using a lower dose (0.60 mg /day), it was found a strong enhance of IL-6 concentration: 13.50 ± 2.52 pg/mL in the supplemented group versus 6.28 ± 0.43 pg/mL in the control, that must be further investigated.…”

Trans-resveratrol alleviates hepatic and renal injury in γ-irradiated rats

“…47,48 Furthermore, t-Res improved the regulation of signaling molecule Nrf-2, an important regulator in the antioxidant response pathway. 49 Besides, t-Res possesses anti-inflammatory effects, as shown in the study of Khalil et al 50 via reducing the levels of pro-inflammatory mediators and greatly enhancing the expression level of SIRT-1 signaling pathway, which subsequently modulates p53 and NF-κB signals. 48 Also, t-Res significantly inhibited the SOCS-3.…”

Resveratrol: A Review on the Biological Activity and Applications

“…After irradiation, RSV 10 or 100 mg/kg was intraperitoneally administered for 30 days. The results highlighted that RSV 100 mg/kg modulated the liver inflammatory profile of immune response and circulating endothelial cells (CECs) population during acute whole-body gamma irradiation [186].…”