Therapeutic efficacy of vitamin E δ-tocotrienol in collagen-induced rat model of arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease primarily involving inflammation of the joints. Although the management of the disease has advanced significantly in the past three decades, there is still no cure for RA. The aim of this study was to determine the therapeutic efficacy of δ-tocotrienol, in the rat model of collagen-induced arthritis (CIA). Arthritis was induced by intradermal injection of collagen type II emulsified in complete Freund's adjuvant. CIA rats were orally treated with δ-tocotrienol (10 mg/kg) or glucosamine hydrochloride (300 mg/kg) from day 25 to 50. Efficacy was assessed based on the ability to reduce paw edema, histopathological changes, suppression of collagen-specific T-cells, and a reduction in C-reactive protein (CRP) levels. It was established that δ-tocotrienol had the most significant impact in lowering paw edema when compared to glucosamine treatment. Paw edema changes correlated well with histopathological analysis where there was a significant reversal of changes in groups treated with δ-tocotrienol. The results suggest that δ-tocotrienol is efficient in amelioration of collagen-induced arthritis. Vitamin E delta-tocotrienol may be of therapeutic value against rheumatoid arthritis.

Figure 1

Effect of delta-tocotrienol on hind-paw edema. Hind-paws on day 50 of the experiment. Normal rats (a) from control group showed no signs of joint inflammation. Gross morphology of the hind-paws of arthritis rats showed maximal swelling and redness over joints (b). Treatment with tocotrienol and glucosamine reduced the severity of paw inflammation ((c) and (d)).

Figure 2

Effect of delta-tocotrienol on body weight changes in arthritis rats. Data are expressed as mean ± standard error. *P < 0.05: arthritis versus other groups.

Figure 3

Histopathological analysis of joint morphology (H&E-200x). (a) Photomicrograph of arthritis group, showing synovial fibrosis (black arrow) and inflammatory infiltrate forming a pannus (red circle), (b) photomicrograph of arthritis + delta-tocotrienol, showing a significant reduction in synovial hyperplasia and inflammation (black arrow) and healthy joint space (black double arrow head), (c) photomicrograph of arthritis with glucosamine group, showing angiogenesis in the form of proliferating blood vessels (blue circle) and surrounding synovial healing scar tissue (black double arrow head), and (d) photomicrograph of control group, showing healthy normal joint space (double arrow head) with no inflammation or hyperplasia.

Figure 4

Proliferation of collagen-stimulated splenocytes from arthritic rats supplemented with delta-tocotrienol and glucosamine. Data are expressed as mean ± standard error. *P < 0.05: arthritis versus other groups; ^◆ P < 0.05: arthritis with tocotrienol versus arthritis with glucosamine groups.

Figure 5

Effect of delta-tocotrienol on C-reactive protein concentration. Data are expressed as mean ± standard error of six rats per group. *P < 0.05: arthritis versus other groups; ^◆ P < 0.05: arthritis with tocotrienol versus arthritis with glucosamine groups.