PURPOSE: This study was undertaken to investigate the effects of gamma linolenic acid (GLA) on inflammation and extracellular matrix (ECM) synthesis in mesangial and tubular epithelial cells under diabetic conditions. MATERIALS AND METHODS: Sprague-Dawley rats were intraperitoneally injected with either a diluent [n=16, control (C)] or streptozotocin [n=16, diabetes (DM)], and eight rats each from the control and diabetic groups were treated with evening primrose oil by gavage for three months. Rat mesangial cells and NRK-52E cells were exposed to medium containing 5.6 mM glucose and 30 mM glucose (HG), with or without GLA (10 or 100 microM). Intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), and fibronectin (FN) mRNA and protein expression levels were evaluated. RESULTS: Twenty-four-hour urinary albumin excretion was significantly increased in DM compared to C rats, and GLA treatment significantly reduced albuminuria in DM rats. ICAM-1, MCP-1, FN mRNA and protein expression levels were significantly higher in DM than in C kidneys, and these increases were significantly abrogated by GLA treatment. In vitro, GLA significantly inhibited increases in MCP-1 mRNA expression and protein levels under high glucose conditions in HG-stimulated mesangial and tubular epithelial cells (p<0.05, respectively). ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1. CONCLUSION: GLA attenuates not only inflammation by inhibiting enhanced MCP-1 and ICAM-1 expression, but also ECM accumulation in diabetic nephropathy.
Animals ; Anti-Inflammatory Agents/*therapeutic use ; Blotting, Western ; Chemokine CCL2/genetics/metabolism ; Diabetic Nephropathies/*drug therapy/*metabolism ; Enzyme-Linked Immunosorbent Assay ; Fibronectins/genetics/metabolism ; Intercellular Adhesion Molecule-1/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; alpha-Linolenic Acid/*therapeutic use

OBJECTIVETo investigate the effects of alpha-linolenic acid (ALA) on inflammation and oxidative stress in the diabetic rats.

METHODSAn experimental type 2 diabetes mellitus model was induced by feeding male SD rats with diet of high fat for 4 weeks and then injected them intraperitoneally with streptozocin (STZ) at 30 mg/kg. Then the animals were randomly divided into three groups (n = 10): control group, diabetic group and ALA group. Four weeks later, tumor necrosis factor (TNF)-a, soluble P-selectin (sP-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), nitric oxide (NO) production, malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in the serum were determined.

RESULTSInflammatory agents including TNF-alpha, sP-selectin and sICAM-1 increased in diabetic rats to compare with control group. Treatment with ALA significantly decreased TNF-alpha, sP-selectin and slCAM-1 to compare with diabetic group. Furthermore, compared with control group, serum MDA production increased whereas NO production, SOD and CAT activities decreased in diabetic rats. Treatment with ALA reduced MDA production, increased NO production, promoted SOD and CAT activities compared with diabetic group.

CONCLUSIONThese results indicate that diet rich in ALA exerted the anti-inflammatory and anti-oxidative effects in diabetic rats, which may be beneficial to the prevention and treatment of diabetes.

Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; Inflammation ; Male ; Malondialdehyde ; blood ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood ; Tumor Necrosis Factor-alpha ; blood ; alpha-Linolenic Acid ; pharmacology ; therapeutic use