Short term effects of dietary fish oil on matrix metalloproteinases in dogs with anterior cruciate ligament disease

Abstract

Matrix metalloproteinases (MMPs) comprise a family of enzymes that degrade extracellular matrix components. Abnormally elevated concentrations of MMPs play key roles in chronic diseases such as cancer and arthritis. Fish oil, containing high amounts of the polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been demonstrated to reduce tissue concentrations of inflammatory mediators tumor necrosis factor (TNF) alpha, urokinase plasminogen activator (uPA), and prostaglandin (PG) E2 that increase with arthritis. These inflammatory mediators are key regulators that increase production of MMPs. Tissue inhibitors of metalloproteinases (TIMPs) down-regulate the activity of MMPs. This study investigated effects of dietary fish oil intake in dogs undergoing surgery for cranial cruciate ligament rupture in a single knee on the response of MMPs to modulation of inflammatory mediators and TIMPs. Twenty-four mature large breed dogs were fed identical maintenance diets that differed only in PUFA content (90mg/kg/day) as fish oil or beef tallow for 63 days. Plasma and synovial fluid from both surgically and non-surgically affected knees were obtained at the start of diet, on the day of surgery, and at 7, 14, 28, and 56 days following surgery. Plasma was analyzed for arachidonic acid, EPA, DHA and bicycloPGE2. Synovial fluid was analyzed for uPA, collagenase (MMP-1, 8, and 13), and pro and active MMP-2 and MMP-9. The fish oil fed group showed significant increases in total plasma EPA and DHA within one week after start of dietary supplementation and through the duration of the study. The fish oil group also showed significant decreases in uPA in non-surgical synovial fluid at day 28, proMMP-2 at days 7 and 14, and proMMP-9 at day 56. The fish oil fed group showed significant increases in non-surgical synovial fluid TIMP activity at day 7 and 28. In conclusion, non-surgical synovial fluid concentrations of uPA and MMPs were decreased and TIMP-2 concentrations were increased by dietary supplementation of EPA and DHA.