Acute Toxicity and Suppressive Effects of a Curcumin Analogue Gamavuton-0 (Gvt-0) On CFA-Induced Arthritis in rats.

ABSTRACT

Gamavuton-0 (GVT-0) is a curcumin analogue, which is synthesized from acetone and vanillin with chloride acid as a catalyst and ethanol as a solvent. The compound has been reported to have an anti-inflammatory effect related to its activity as COX-2 inhibitor, anti-oxydant, and radical scavanger. This study was aimed to investigate whether the GVT-0 has a suppressive effect on rheumatoid arthritis (RA) as one of chronic inflammatory disorders in a rat model. Wistar rats were immunized with Complete Freund’s Adjuvant (CFA). After a second CFA immunization, the rats were treated with GVT-0 orally at 10, 20, 40, 80 mg/kg BW once a day for 21 days, while the positive control received methotrexate 0.22 mg/kg BW. The animal paws were evaluated macroscopically for redness, swelling and deformities with Smit method to assess arthritic index. The anti-inflammatory effect of GVT-0 was evaluated using a plethismograph by measuring rat paw edema, while it’s effects on the level of TNF- and IL-1β in the ankle joints were examined using an ELISA method. The effect of GVT-0 on cartilage destruction was assesed histologically using Safranin-O staining. The acute toxicity test was also performed to assess the safety potential of the compound. The oral treatment of rats for 21 days with various doses of GVT-0 significantly suppressed the progession of RA indicated by the improvement of arthritic index and decreased the inflammation in rat paws. The compound also decreased the level of TNFα and IL-1β in ankle joints. The destruction of cartilage was significantly reduced in rats ankles after treatment with GVT-0. In toxicological assay, the apparent LD50 value of GT-0 was regarded as 7,29 g/kg BW and was classiefied to be practically non-toxic. The results suggest that GVT-0 is safe and potential to modify the progression of rheumatoid arthritis and can be developed as a new disease modifying anti rheumatoid arthritis drugs (DMARDs).