Gamma linolenic acid exerts anti-inflammatory and anti-fibrotic effects in diabetic nephropathy.
OBJECTIVE
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.


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 μM). 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.


CONCLUSIONS
GLA attenuates not only inflammation by inhibiting enhanced MCP-1 and ICAM-1 expression, but also ECM accumulation in diabetic nephropathy.
Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, Korea.
Do-Hee
DH
Kim
Tae-Hyun
TH
Yoo
Soon Ha
SH
Lee
Hye Young
HY
Kang
Bo Young
BY
Nam
Seung Jae
SJ
Kwak
Jwa-Kyung
JK
Kim
Jung Tak
JT
Park
Seung Hyeok
SH
Han
Shin-Wook
SW
Kang
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D017962:alpha-Linolenic Acid / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D005353:Fibronectins; D017962:alpha-Linolenic Acid; D018799:Intercellular Adhesion Molecule-1