Gamma Linolenic Acid Exerts Anti-Inflammatory and Anti-Fibrotic Effects in Diabetic Nephropathy

Abstract

PurposeThis 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 MethodsSprague-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.ResultsTwenty-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.ConclusionGLA attenuates not only inflammation by inhibiting enhanced MCP-1 and ICAM-1 expression, but also ECM accumulation in diabetic nephropathy.

18-Carbon polyunsaturated fatty acids ameliorate palmitate-induced inflammation and insulin resistance in mouse C2C12 myotubes

“…Our previous results revealed that GLA inhibits inflammatory responses through inactivation of NF-κB and AP-1 by suppressing oxidative stress and the MAPK signal pathway in lipopolysaccharideinduced RAW 264.7 macrophages [25]. Moreover, in STZ-induced diabetic nephropathy, GLA exerts anti-inflammatory effects [24]. The data presented herein showed that oral administration of GLA-rich borage oil decreased IL-6 and TNF-α expression in GA muscles of HFD/ STZ-induced diabetic mice.…”

“…Supplementation with GLA to offset the decline in activity of delta-6-desaturase has therapeutic benefits in several inflammation-related diseases, including asthma, ulcerative colitis, rheumatoid arthritis, and atopic dermatitis, cardiovascular disease and cancer [22,23]. A renoprotective property of GLA was also shown in an animal model of diabetic nephropathy, which was attributed to the anti-inflammatory and antifibrotic actions of GLA [24]. Furthermore, data from our previous study showed that GLA is more potent than LA in inhibition of lipopolysaccharide-induced NF-κB transcriptional activity and inflammatory events in RAW 264.7 macrophages [25].…”

Synergistic Effects of Leflunomide and Benazepril in Streptozotocin-Induced Diabetic Nephropathy

“…MCP-1 is a potent chemoattractant and adhesion molecule for monocytes and macrophages, and there is overwhelming evidence that the upregulation of MCP-1 is closely associated with influx of inflammatory cells and renal scarring in DN [7,8]. Recently, increasing evidence suggests that TLR-2 triggers a renal inflammatory response in DN [9].…”

Gamma-linolenic acid inhibits hepatic PAI-1 expression by inhibiting p38 MAPK-dependent activator protein and mitochondria-mediated apoptosis pathway

“…A recent study suggested GLA exerts anti-inflammatory and anti-fibrotic effects in experimental diabetic nephropathy and in high glucose stimulated renal cells [23]. Also, it was reported that GLA plays a role in the tumor progression [25], regulation of macrophages [45] and prevention of fatty liver in mice [24].…”

“…In a previous study, GLA was shown to abrogate renal fibrosis in a 5/6 nephrectomy model [21], and other investigations demonstrated that GLA treatment improved autoimmune diseases and diabetic neuropathy via an anti-inflammatory mechanism [22]. A recent study has indicated that GLA exerts anti-inflammatory and anti-fibrotic effects in experimental diabetic nephropathy and in high-glucose-stimulated renal cells [23]. GLA has also been shown to have a preventive effect against conjugated linoleic acid-induced fatty liver in mice [24].…”