Efeitos da galactomanana de Cyamopsis tetragonolobus na osteoartrite induzida por transecção do ligamento cruzado anterior em ratos

Abstract

Using the osteoarthritis (OA) model induced by anterior cruciate ligament transection (ACLT) in rats, we have demonstred that guar gum (GG), a galactomannan extracted from Cyamopsis tetragonolobus seeds, displays analgesic activity similar to Hylan G-F 20, a hyaluronate derivate used as local therapy in human OA. In the same model, we objective to develop a parametric biochemical method for joint lesion evaluation, and to investigate the mechanism for analgesia and the chondroprotective effect of GG. Wistar rats subjected to ACLT (OA group) were sacrificed at different endpoints. Joint pain was daily measured using the test for articular incapacitation in rats, until 70 days. Joint lavage was used for NO determination. Articular cartilage was evaluated by the chondroitin-sulfate (CS) content and determination of its molar weight. Histophatologic analysis using the OARSI score system was also performed. Sham-operated groups were used for comparison. In the studies of joint pain, OA groups received indomethacin (2mg/kg/d s.c.), meloxicam (6mg/kg/d i.p.), tadalafil (0.5mg/kg/d p.o.) between days 4 and 7.Morphine (200µg i.art.) was given at day 4 only, 30 min before the pain evaluation. Naloxone (500µg i. art.) was given 15 min prior morphine. Sodium alendronate (30 or 240µg i. art.) was given prophilactically, starting 3 days prior ACLT, and repeated at each 3 days, until day 6. Original or chemically modified GG (100μg/50μl i. art.) was given as a single dose at day 4. Galactose or mannose was co-administred (500μg/50μl i. art.) with original GG. In the study of chondroprotection, GG (100μg/50μl i. art.) was given once weekly, starting at day 14, during 8 weeks. Non-treated animals (NT) received vehicle (saline). OA animals presented maximal joint pain and NO release in the first week. Both CS content and molar weight were higher at day 70 (p<0.05). At this endpoint, important histopathologic changes were found in the OA group. Indomethacin, meloxican, tadalafil and morphine significantly reduced joint pain (p<0.05). Naloxone reverted the effect of morphine. Alendronate prevented the joint pain development. Modified GG structures were unable to promote analgesia. The analgesic effect of unmodified GG could be reverted by galactose (p<0.01), but not by mannose. GG treatment prevented the CS changes, and it reduced the histopatologic lesion (p<0.05). CS changes seem to reflect the tecidual damage, and may be used as an index for the joint lesion. The analgesic efficacy of GG is due to galactose residues. In addition, the chondroprotective effect by GG was demonstrated. This is an important contribution to propose GG as an antiarthrosic drug.