2005
DOI: 10.1681/asn.2004111011
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Methotrexate Prevents Renal Injury in Experimental Diabetic Rats via Anti-Inflammatory Actions

Abstract: Recent studies suggested the involvement of inflammatory processes in the pathogenesis of diabetic nephropathy. Methotrexate (MTX), a folic acid antagonist, is widely used for the treatment of inflammatory diseases. Recently, it has been shown that treatment with low-dose MTX reduces the cardiovascular mortality in patients with rheumatoid arthritis, suggesting that MTX has anti-atherosclerotic effects via its anti-inflammatory actions. This study was designed to determine the antiinflammatory effects of this … Show more

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Cited by 78 publications
(68 citation statements)
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“…The role of inflammation in the progression of DN can be implied from the studies described above. The importance of the inflammatory component has been further substantiated in intervention studies, demonstrating an amelioration of diabetic tissue damage by anti-inflammatory drugs such as mycophenolate mofetil or low-dose methotrexate (29,30). A reduction in NF-B activation and subsequent reduction in macrophage and T-cell infiltration may help explain the observed benefit.…”
Section: Discussionmentioning
confidence: 98%
“…The role of inflammation in the progression of DN can be implied from the studies described above. The importance of the inflammatory component has been further substantiated in intervention studies, demonstrating an amelioration of diabetic tissue damage by anti-inflammatory drugs such as mycophenolate mofetil or low-dose methotrexate (29,30). A reduction in NF-B activation and subsequent reduction in macrophage and T-cell infiltration may help explain the observed benefit.…”
Section: Discussionmentioning
confidence: 98%
“…Diabetesinduced glomerular macrophage infiltration, ICAM-1 expression and NF-kB activation associated with albuminuria, mesangial expansion, glomerular hypertrophy and glomerular expression of collagen and TGF-b in the kidney have been partly or completely prevented by antiinflammatory agents, such as mycophenolate mofetil, erythromycin or methotrexate. [75][76][77] Prevention of diabetes-induced renal inflammation and associated renal damage in ICAM-1-or MCP-1-deficient animals provides further evidence of the participation of the inflammatory process in the pathogenesis of diabetic nephropathy. 78,79 Several lines of evidence have been shown to support the concept that a local inflammatory process is involved in the pathogenesis of DR. 80 Studies in humans using material from a vitrectomy or postmortem specimens from diabetic donors have demonstrated an association between inflammatory markers and the presence of DR. An increased expression of ICAM-1, which facilitates the trafficking of leukocytes into the retina, has been demonstrated in retinal blood vessels of post-mortem specimens from diabetic donors 81 and also in vitreous tissue of diabetic patients.…”
Section: Contribution Of Inflammation and Oxidative Stress To Dr And mentioning
confidence: 99%
“…[5][6][7][8] For example, mycophenolate mofetil, methotrexate, or irradiation reduce urinary albumin excretion, and glomerulosclerosis in rats with streptozotocin-induced diabetes. 9,10 Yet, the molecular and cellular mechanisms of intrarenal inflammation in diabetic nephropathy remain poorly characterized. Patients with diabetic nephropathy have increased serum levels of acute phase markers of inflammation but this may not represent intrarenal inflammation.…”
mentioning
confidence: 99%