The role of Th1/Th2/Th17 cytokines and antioxidant defense system in mediating the effects of lemon and grapefruit peel hydroethanolic extracts on adjuvant-induced arthritis in rats

Abstract

The present investigation was performed to assess the effects of lemon and grapefruit peel hydroethanolic extracts on arthritic indices, T helper (Th)1/Th2/Th17 cytokines, oxidative stress, and antioxidant defense system in arthritic rats. The male Wistar rats, with rheumatoid arthritis induced by subcutaneous injection of 0.2 ml Freund's complete adjuvant into a footpad of the right hind leg on two consecutive days, were orally treated with lemon and grapefruit peel hydroethanolic extract at a dose level of 100 mg/kg bw/day for 9 and 18 days. The treatments of arthritic rats with lemon and grapefruit peel hydroethanolic extracts significantly reduced the right hind paw circumference, volume, and thickness. The treatments also significantly decreased the elevated total leucocyte count and serum rheumatoid factor, PGE2, Th1 cytokine (TNF-α), and Th17 cytokine (IL-17) levels, while they increased the lowered serum Th2 anti-inflammatory cytokines (IL-10 and IL-13) levels in arthritic rats after 9 and 18 days. Furthermore, the treatments significantly decreased the elevated lipid peroxidation and nitric oxide hepatic contents, while they increased the lowered glutathione content and glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase activities. In conclusion, lemon or grapefruit peel hydroethanolic extracts have anti-arthritic effects which may be mediated via modulation of Th1/Th2/Th17 cytokine production and enhancement of the antioxidant defense system.