Therapeutic Role of Resveratrol and Quercetin on Aortic Fibroblasts of Psammomys obesus After Oxidative Stress by Hydrogen Peroxide

Abstract

In our study, we propose to analyze the effects of resveratrol (RES) and quercetin (QRC) on proliferation markers, oxidative stress, apoptosis, and inflammation of aortic fibroblasts of Psammomys obesus after induced oxidative stress by hydrogen peroxide (H2O2). Fibroblasts were incubated in RES 375 μM and QRC 0.083 μM for 24 hours after exposure to H2O2 1.2 mM for 6 hours. We performed the proliferation rate, cells viability, morphological analyses, cytochrome c, Akt, ERK1/2, and p38 MAPK quantification. The redox status was achieved by proportioning of malondialdehyde, nitric monoxide, advanced oxidation protein products, carbonyl proteins, catalase, and superoxide dismutase activity. The inflammation was measured by TNFα, MCP1, and NF-kB assay. The extracellular matrix (ECM) remodeling was performed by SDS-PAGE. Stressed fibroblasts showed a decrease of cell proliferation and viability, hypertrophy and oncosis, chromatin hypercondensation and increase of cytochrome c release characteristic of apoptosis, activation of ERK1/2 and Akt pathway, and decreases in p38 MAPK pathways marking the cellular resistance. The redox state was disrupted by increased malondialdehyde, nitric monoxide, advanced oxidation protein products, carbonyl protein production, catalase and superoxide dismutase activity, and a decreased production of proteins including collagens. Inflammation state was marked by MCP-1, TNFα, and NF-kB increase. Treatment of fibroblasts stressed by RES and QRC inverted the oxidative stress situation decreasing apoptosis and inflammation, and improving the altered redox status and rearrangement of disorders observed in extracellular matrix. H2O2 induced biochemical and morphological alterations leading to apoptosis. An improved general condition is observed after treatment with RES and QRC; this explains the antioxidant and antiapoptotic effects of polyphenols.

Possible Prevention of Reactive Oxygen Species Induced Human Trabecular Meshwork Cell Damage by Resveratrol and Ascorbic Acid.

“…Similar findings were observed by Boumaza S, and his colleagues, in a study conducted to see protective role of resveratrol on fibroblast cells induced oxidation state. 16 , Similar findings were also noted in other studies 17,18 These results prove the efficacy of Resveratrol and Ascorbate as antioxidants. As ROS play pivotal role in POAG, and anti ROS activity of Resveratrol and Ascorbate may be exploited for its prevention and treatment.…”

Resveratrol Ameliorates the Severity of Fibrogenesis in Mice with Experimental Chronic Pancreatitis

“…The results of our cell viability assay revealed a cell‐type specificity of resveratrol as it was approximately five times less cytotoxic to pancreatic acini when comparing to PSCs, which possess an ECM‐producing phenotype. When administered in vivo, the oral consumption of resveratrol did not result in adverse or harmful consequence to the animals in the present trial, so as in the chronic studies of others . Taken together, resveratrol is potentially a pharmacologic intervention for the treatment of chronic pancreatitis.…”

Quercetin Remodels the Tumor Microenvironment To Improve the Permeation, Retention, and Antitumor Effects of Nanoparticles

“…33 Our data exhibited the ability of LCP-QP to down regulate the α -SMA fibroblast populations and normalize the collagen content in the tumor tissue. This was consistent with the results found in human corneal fibroblasts in which quercetin is a key regulator of fibrotic markers and ECM assembly.…”

“…12 Quercetin has demonstrated to reverse the oxidative stress environment, decreasing inflammation as well as inducing rearrangement of extracellular matrix (ECM) in aortic fibroblast disorders. 33 Our data exhibited the ability of LCP-QP to down regulate the α-SMA fibroblast populations and normalize the collagen content in the tumor tissue. This was consistent with the results found in human corneal fibroblasts in which quercetin is a key regulator of fibrotic markers and ECM assembly.…”