Use of Resveratrol Self-Emulsifying Systems in T/C28a2 Cell Line as Beneficial Effectors in Cellular Uptake and Protection Against Oxidative Stress-Mediated Death.

Solenn Le Clanche,Tristan Cheminel,Didier Borderie,François Rannou,Christine Charrueau,Dominique Bonnefont-Rousselot

doi:10.3389/fphar.2018.00538

Abstract

Osteoarthritis (OA) is the most prevalent rheumatic disease in the world. Although its etiology is still unknown, one of the key processes in OA progression and development is oxidative stress. In this context, resveratrol, a well-known anti-oxidant from the stilbene family, could be of particular interest in future OA therapeutic strategies. However, currently, because of its low bioavailability, use of resveratrol in human health is very limited. In this study, we tested two resveratrol self-emulsifying systems previously developed in our laboratory in order to determine if they could improve cellular uptake of resveratrol in a human immortalized chondrocytic cell line (T/C28a2) and enhance protection against oxidative stress. Our results showed that resveratrol self-emulsifying systems were able first to increase cellular tolerance towards resveratrol, and thus decrease resveratrol intrinsic cellular toxicity, allowing the use of higher concentrations, second, to increase resveratrol uptake in membrane and intracellular fractions, and finally, to improve protection against oxidative stress-mediated death in human immortalized chondrocytic cell line T/C28a2. These data suggest that new formulations of resveratrol could be considered as potential beneficial effectors in future OA treatments.

Highlights

Osteoarthritis is a degenerative disease of the joint, characterized by irreversible cartilage degradation
Chondrocyte apoptosis is a severe event in OA progression because these cells have a very low turn-over so their loss implies an important decrease in extra-cellular matrix (ECM) components synthesis, leading to a general failure of the articular cartilage (Hwang and Kim, 2015)
25 μM of resveratrol in NE 1 induced a significant increase in resveratrol concentration after 180 min (p < 0.05 vs. 25 μM resveratrol-1% ethanol). 25 and 50 μM of resveratrol brought by NE 2 induced a significant increase in resveratrol concentrations after incubation for 20, 60, and 180 min compared with 25 μM resveratrol-1% ethanol (p < 0.05) (Figure 2B)

Summary

Introduction

Osteoarthritis is a degenerative disease of the joint, characterized by irreversible cartilage degradation. It is the most prevalent rheumatic disease in the world (Muirden, 2005; Vos et al, 2012), generally associated with aging, making it a real major health issue. Chondrocyte apoptosis is a severe event in OA progression because these cells have a very low turn-over so their loss implies an important decrease in ECM components synthesis, leading to a general failure of the articular cartilage (Hwang and Kim, 2015). In an experimental rabbit model of OA, Wang et al (2012) have demonstrated that resveratrol was responsible for a decrease in cartilage destruction, chondrocyte apoptosis, and a reduction of overproduced nitric oxide in synovial fluid

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